Trial Outcomes & Findings for Study to Evaluate H56:IC31 in Preventing Rate of TB Recurrence (NCT NCT03512249)

Last Updated: 2026-02-24

Results Overview

To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for acid fast bacilli (AFB) on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative): Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

831 participants

Primary outcome timeframe

During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination

Results posted on

2026-02-24

Participant Flow

Various methods of recruitment were used i.e., advertising, referrals, or proposition. All recruitment materials were approved by IRB and/or IEC. Interested TB patients from local TB clinics were invited to participate in the informed consent process. Recruitment commenced on 31 Jan 2019 and ended on 03 Sep 2021.

Participant milestones

Participant milestones
Measure	H56:IC31 The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo Sterile saline for injection Placebo: Sterile saline for injection
Overall Study STARTED	415	416
Overall Study COMPLETED	358	384
Overall Study NOT COMPLETED	57	32

Reasons for withdrawal

Reasons for withdrawal
Measure	H56:IC31 The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo Sterile saline for injection Placebo: Sterile saline for injection
Overall Study Lost to Follow-up	19	6
Overall Study Death	2	6
Overall Study Withdrawal by Subject	7	3
Overall Study Recurrent TB	19	12
Overall Study Other	10	5

Baseline Characteristics

Study to Evaluate H56:IC31 in Preventing Rate of TB Recurrence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	H56:IC31 n=415 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=416 Participants Sterile saline for injection Placebo: Sterile saline for injection	Total n=831 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=58 Participants	0 Participants	0 Participants n=1 Participants
Age, Categorical Between 18 and 65 years	415 Participants n=58 Participants	416 Participants	831 Participants n=1 Participants
Age, Categorical >=65 years	0 Participants n=58 Participants	0 Participants	0 Participants n=1 Participants
Age, Continuous	34.3 years STANDARD_DEVIATION 11.2 • n=58 Participants	35.1 years STANDARD_DEVIATION 11.0	34.7 years STANDARD_DEVIATION 11.1 • n=1 Participants
Age, Customized Age group · 18-35 years	247 Participants n=58 Participants	233 Participants	480 Participants n=1 Participants
Age, Customized Age group · 36-60 years	168 Participants n=58 Participants	183 Participants	351 Participants n=1 Participants
Sex: Female, Male Female	112 Participants n=58 Participants	117 Participants	229 Participants n=1 Participants
Sex: Female, Male Male	303 Participants n=58 Participants	299 Participants	602 Participants n=1 Participants
Race/Ethnicity, Customized Black or African American	276 Participants n=58 Participants	273 Participants	549 Participants n=1 Participants
Race/Ethnicity, Customized Mixed Cape Ancestry	132 Participants n=58 Participants	142 Participants	274 Participants n=1 Participants
Race/Ethnicity, Customized Other	7 Participants n=58 Participants	1 Participants	8 Participants n=1 Participants
Region of Enrollment Tanzania	92 Participants n=58 Participants	106 Participants	198 Participants n=1 Participants
Region of Enrollment South Africa	323 Participants n=58 Participants	310 Participants	633 Participants n=1 Participants
Height	166.52 cm STANDARD_DEVIATION 8.85 • n=58 Participants	166.22 cm STANDARD_DEVIATION 8.94	166.37 cm STANDARD_DEVIATION 8.89 • n=1 Participants
Weight	58.67 kg STANDARD_DEVIATION 10.01 • n=58 Participants	58.12 kg STANDARD_DEVIATION 10.92	58.39 kg STANDARD_DEVIATION 10.47 • n=1 Participants
Body Mass Index (BMI)	21.17 kg/m^2 STANDARD_DEVIATION 3.41 • n=58 Participants	21.04 kg/m^2 STANDARD_DEVIATION 3.80	21.11 kg/m^2 STANDARD_DEVIATION 3.61 • n=1 Participants
BMI group 13 to 25 kg/m^2	374 Participants n=58 Participants	365 Participants	739 Participants n=1 Participants
BMI group 25 kg/m^2 and above	41 Participants n=58 Participants	51 Participants	92 Participants n=1 Participants
Smoking status Non-smoker	149 Participants n=58 Participants	175 Participants	324 Participants n=1 Participants
Smoking status Smoker	205 Participants n=58 Participants	180 Participants	385 Participants n=1 Participants
Smoking status Ex-smoker	61 Participants n=58 Participants	61 Participants	122 Participants n=1 Participants
Enrollment per trial site A1	47 Participants n=58 Participants	61 Participants	108 Participants n=1 Participants
Enrollment per trial site A2	69 Participants n=58 Participants	70 Participants	139 Participants n=1 Participants
Enrollment per trial site A3	128 Participants n=58 Participants	101 Participants	229 Participants n=1 Participants
Enrollment per trial site A4	46 Participants n=58 Participants	45 Participants	91 Participants n=1 Participants
Enrollment per trial site A5	92 Participants n=58 Participants	106 Participants	198 Participants n=1 Participants
Enrollment per trial site A6	33 Participants n=58 Participants	33 Participants	66 Participants n=1 Participants
Anaemia Yes	37 Participants n=58 Participants	41 Participants	78 Participants n=1 Participants
Anaemia No	378 Participants n=58 Participants	375 Participants	753 Participants n=1 Participants
Diabetes mellitus Yes	17 Participants n=58 Participants	18 Participants	35 Participants n=1 Participants
Diabetes mellitus No	398 Participants n=58 Participants	398 Participants	796 Participants n=1 Participants
Comorbidity Yes	120 Participants n=58 Participants	114 Participants	234 Participants n=1 Participants
Comorbidity No	295 Participants n=58 Participants	302 Participants	597 Participants n=1 Participants

PRIMARY outcome

Timeframe: During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination

Population: The primary analysis set for efficacy was the modified Intention to treat (mITT) analysis set. The mITT analysis set included all randomized participants except for those with TB disease recurrence before V6=Day 70 (or 14 days after the second injection for those who received both injections). Participants were evaluated as randomized.

Outcome measures

Outcome measures
Measure	H56:IC31 n=400 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=406 Participants Sterile saline for injection Placebo: Sterile saline for injection
Rate of TB Disease Recurrence (Relapse or Reinfection), Defined as TB Diagnosed by Confirmation of Mtb by Culture of Sputum. TB recurrence present	23 Participants	14 Participants
Rate of TB Disease Recurrence (Relapse or Reinfection), Defined as TB Diagnosed by Confirmation of Mtb by Culture of Sputum. Censored without TB recurrence	377 Participants	392 Participants

SECONDARY outcome

Timeframe: Day 0 through Day 70

Population: Safety analysis set

Solicited adverse events were infection site reactions (redness, swelling and tenderness/pain) and systemic adverse events (AEs) (fever, arthralgia, myalgia, fatigue, headache, rash, chills, and nausea). All participants were provided with a diary, a thermometer to record axillary temperature, a ruler to measure injection site redness and swelling, and instructions on using the diary for the first 7 days after each vaccination. In the period from 8 days after the vaccinations until the diary review at 14 days after each vaccination, the participants were instructed to fill in the diary only in case of an AE.

Outcome measures

Outcome measures
Measure	H56:IC31 n=415 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=416 Participants Sterile saline for injection Placebo: Sterile saline for injection
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Any adverse events within 14 days after vaccination	266 participants	228 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term General disorders and administration conditions	212 participants	161 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Fatigue	112 participants	104 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site pain	141 participants	57 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site erythema	77 participants	36 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site swelling	72 participants	23 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Pyrexia	26 participants	23 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Chills	20 participants	18 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Chest pain	6 participants	5 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Hypothermia	1 participants	5 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Asthenia	2 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Malaise	3 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Influenza like illness	3 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Pain	0 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site pruritus	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site rash	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Peripheral swelling	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site discoloration	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Oedema peripheral	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Suprapubic pain	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Vessel puncture site erythema	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Vessel puncture site pain	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Vessel puncture site swelling	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Musculoskeleta and connective tissue disorders	111 participants	94 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Myalgia	89 participants	57 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Arthralgia	68 participants	61 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Back pain	9 participants	9 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Musculoskeletal pain	4 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Neck pain	4 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Muscle spasms	1 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Pain in extremity	1 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Musculoskeletal chest pain	0 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Muscle fatigue	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Musculoskeletal stiffness	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Nervous system disorders	96 participants	104 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Headache	95 participants	103 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dizziness	3 participants	4 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Paraesthesia	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Gastrointestinal disorders	70 participants	65 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Nausea	52 participants	47 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Abdominal pain	10 participants	8 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Diarrhoea	2 participants	7 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Toothache	5 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Abdominal pain upper	2 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Vomiting	2 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dyspepsia	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Abdominal discomfort	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Abdominal pain lower	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Anal fissure	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Constipation	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Gastritis	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tongue eruption	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tongue ulceration	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Skin and subcutaneous tissue disorders	25 participants	23 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Rash	15 participants	14 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Rash papular	3 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Pruritus generalised	1 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dermatitis	0 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Hyperhidrosis	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Pruritus	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Angioedema	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dermatitis allergic	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Night sweats	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Papule	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Rash erythematous	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Infections and infestations	22 participants	20 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Upper respiratory tract infection	3 participants	6 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Gastroenteritis	4 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Influenza	2 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Lower respiratory tract infection	2 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Rhinitis	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Urethritis	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Urinary tract infection	0 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Abscess	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Anal abscess	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Bronchitis	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Corona virus infection	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injection site pustule	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Nasopharyngitis	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Otitis externa	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Rash pustular	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Respiratory tract infection	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Sinusitis	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tinea pedis	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tinea versicolour	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tonsillitis	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tracheobronchitis viral	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Viral upper respiratory tract infection	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Respiratory, thoracic and mediastinal disorders	8 participants	10 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Cough	4 participants	4 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Rhinorrhoea	0 participants	4 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Oropharyngeal pain	0 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Bronchospasm	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dyspnoea	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Epistaxis	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Productive cough	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Throat irritation	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Injury, poisoning and procedural complications	8 participants	6 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Joint injury	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Ligament sprain	0 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Limb injury	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Gun shot wound	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Lip injury	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Muscle strain	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Repetitive strain injury	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Soft tissue injury	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Stab wound	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Wound	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Wrist fracture	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Investigations	6 participants	5 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Alanine aminotransferase increased	2 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Aspartate aminotransferase increased	1 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Gamma-glutamyltransferase increased	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Blood creatinine increased	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Blood pressure systolic increased	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Glucose urine	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Hepatic enzyme increased	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Neutrophil count increased	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Platelet count decreased	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term White blood cell count decreased	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Vascular disorders	3 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Hypertension	2 participants	3 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Hypotension	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Reproductive system and breast disorders	4 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dysmenorrhoea	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Breast pain	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Genital rash	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Blood and lymphatic system disorders	3 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Neutropenia	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Neutrophilia	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Eye disorders	2 participants	2 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Asthenopia	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Eye pain	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Eye pruritus	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Pinguecula	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Metabolism and nutrition disorders	2 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Decreased appetite	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Diabetes mellitus	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Hyperglycaemia	0 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Cardiac disorders	2 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Palpitations	1 participants	1 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Tachycardia	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Ear and labyrinth disorders	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Ear pain	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Immune system disorders	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Seasonal allergy	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Psychiatric disorders	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Insomnia	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Post-traumatic stress disorder	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Renal and urinary disorders	2 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Dysuria	1 participants	0 participants
Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term Proteinuria	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 0 through Day 70

Population: Safety analysis set

Treatment emergent AEs, AEs within 14 days after vaccination, solicited AEs and solicited SAEs occurring within the 7 days after each vaccination, and unsolicited AEs and SAEs occurring within the first 14 days after each vaccination are summarized.

Outcome measures

Outcome measures
Measure	H56:IC31 n=415 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=416 Participants Sterile saline for injection Placebo: Sterile saline for injection
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations AE outcome unknown	0 participants	3 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations All adverse events within 14 days after vaccination	266 participants	228 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Solicited AEs	239 participants	195 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Adverse event of special interest	0 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Serious adverse event (SAE)	0 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Fatal AE	0 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Related AE	240 participants	190 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Related SAE	0 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations SUSAR	0 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations AE leading to discontinuation of IMP	0 participants	1 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations AE leading to discontinuation of trial	0 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Severe AE	3 participants	0 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Moderate AE	54 participants	61 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations Mild AE	254 participants	212 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations AE not recovered/not resolved	9 participants	6 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations AE recovered/resolved with sequelae	0 participants	2 participants
Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations AE recovered/resolved	263 participants	223 participants

SECONDARY outcome

Timeframe: Day 0 through Day 421

Population: Safety analysis set

Number of participants with serious adverse events including medically important events occurring after the 1st vaccination through the end of the trial, comparing H56:IC31 to placebo.

Outcome measures

Outcome measures
Measure	H56:IC31 n=415 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=416 Participants Sterile saline for injection Placebo: Sterile saline for injection
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial SAE leading to discontinuation of trial	3 participants	6 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Intensity: Severe	13 participants	10 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Any serious adverse event	14 participants	12 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Fatal SAE	2 participants	6 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Related SAE	0 participants	0 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial SUSAR	0 participants	0 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial SAE leading to discontinuation of IMP	0 participants	3 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Intensity: Moderate	1 participants	2 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Recovered/resolved with sequelae	3 participants	1 participants
Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial Recovered/resolved	9 participants	5 participants

SECONDARY outcome

Timeframe: Day 70 through Day 421

Population: mITT analysis set. The mITT analysis set included all randomized participants except for those with TB disease recurrence before V6 = Day70 (or 14 days after the second injection for those who received both injections). Participants were evaluated as randomized.

Rate of TB relapse defined as subjects meeting the primary endpoint of TB disease recurrence, AND determined by whole genome sequencing (WGS) of the Mtb isolate to be the same strain of Mtb as in the subject's original isolate from the time of diagnosis

Outcome measures

Outcome measures
Measure	H56:IC31 n=400 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=406 Participants Sterile saline for injection Placebo: Sterile saline for injection
Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Relapse TB relapse present	12 Participants	6 Participants
Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Relapse Censored without TB relapse	388 Participants	400 Participants

SECONDARY outcome

Timeframe: Day 70 through Day 421

Population: mITT analysis set: The mITT analysis set included all randomized participants except for those with TB disease recurrence before V6 = Day70 (or 14 days after the second injection for those who received both injections). Participants were evaluated as randomized.

Rate of TB disease reinfection defined as subjects meeting the primary endpoint of TB disease recurrence, AND determined by WGS of the Mtb isolate to be a different strain than in the subject's original isolate from the time of diagnosis.

Outcome measures

Outcome measures
Measure	H56:IC31 n=400 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=406 Participants Sterile saline for injection Placebo: Sterile saline for injection
Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Reinfection TB reinfection present	8 Participants	7 Participants
Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Reinfection Censored without TB reinfection	392 Participants	399 Participants

SECONDARY outcome

Timeframe: Day 0 through Day 70

Population: Immunogenicity analysis set: The immunogenicity analysis set consisted of all participants from the mITT population who received both doses of H56:IC31 or placebo and who were included in the immunogenicity cohort (= the first 100 randomized participants at 2 specific sites).

Antigen-specific cell-mediated immune responses by whole blood intracellular cytokine staining (WB ICS) at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70) in the immunogenicity cohort. Variables of interest for assessment of antigen specific cell mediated immune response to vaccination were the percentage of CD4+ and CD8+ cells that express IL-2, IFN-gamma, TNF, and IL-17 in the following combinations: H56 protein-specific CD4+ T cells expressing the total cytokine response, i.e., any combination of IL-2, IFN-gamma, TNF, and/or IL-17 H56 protein-specific CD4+ T cells co-expressing IL-2 and TNF H56 protein-specific CD4+ T cells co-expressing IL-2, IFN-gamma and TNF H56 protein-specific CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF, and/or IL-17 (total response)

Outcome measures

Outcome measures
Measure	H56:IC31 n=43 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=50 Participants Sterile saline for injection Placebo: Sterile saline for injection
Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Absolute Values) CD4+ T-cells expressing any combination of IL-2, IFN-gamma, TNF-α, IL-17 Visit 3 (Day 0/Baseline)	0.074 percentage of cells Interval 0.048 to 0.139	0.093 percentage of cells Interval 0.044 to 0.18
Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Absolute Values) CD4+ T-cells expressing any combination of IL-2, IFN-gamma, TNF-α, or IL-17 Visit 6 (Day 70)	0.328 percentage of cells Interval 0.165 to 0.506	0.088 percentage of cells Interval 0.061 to 0.171
Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Absolute Values) CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF-α, or IL-17 Visit 3(Day 0) Baseline	0.088 percentage of cells Interval 0.039 to 0.184	0.058 percentage of cells Interval 0.03 to 0.154
Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Absolute Values) CD8+ T cells expressing any combination of IL-2, IFN-gamma, TNF-α, or IL-17 Visit 6 (Day 70)	0.157 percentage of cells Interval 0.058 to 0.345	0.072 percentage of cells Interval 0.027 to 0.288

SECONDARY outcome

Timeframe: Day 0 through Day 70

Antigen-specific antibody responses (anti-H56 IgG) assessed by IgG ELISA of plasma samples at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70). Summary of immune response at Visit 3 (Day 0/Baseline) and Visit 6 (Day 70) as well as fold increase from Baseline to Day 70.

Outcome measures

Outcome measures
Measure	H56:IC31 n=43 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=50 Participants Sterile saline for injection Placebo: Sterile saline for injection
Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Absolute Values) Anti-H56 IgG (EU/mL) Visit 6 (Day 70)	6.7 EU/mL Interval 1.6 to 30.6	2.2 EU/mL Interval 1.1 to 3.9
Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Absolute Values) Anti-H56 IgG (EU/mL) Visit 3 (Day 0/Baseline)	4.2 EU/mL Interval 1.6 to 6.1	2.9 EU/mL Interval 1.4 to 5.8

SECONDARY outcome

Timeframe: Day 0 through Day 70

Outcome measures

Outcome measures
Measure	H56:IC31 n=43 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=50 Participants Sterile saline for injection Placebo: Sterile saline for injection
Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Fold Increase) CD4+ T cells expressing any combination of IL-2, IFN-γ, TNF-α, IL-17 Fold increase Day 0 -Day 70	3.8 Fold increase Interval 2.4 to 7.8	1.0 Fold increase Interval 0.7 to 1.5
Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Fold Increase) CD8+ T cells expressing any combination of IL-2, IFN-γ, TNF-α, IL-17 Fold increase Day 0 -Day 70	1.2 Fold increase Interval 0.8 to 2.4	1.5 Fold increase Interval 0.6 to 3.2

SECONDARY outcome

Timeframe: Day 0 through Day 70

Outcome measures

Outcome measures
Measure	H56:IC31 n=43 Participants The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=50 Participants Sterile saline for injection Placebo: Sterile saline for injection
Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Fold Increase From Baseline to Visit 6 [Day 70])	1.8 Fold increase Interval 1.0 to 6.1	0.6 Fold increase Interval 0.4 to 1.0

Adverse Events

H56:IC31

Serious events: 14 serious events

Other events: 300 other events

Deaths: 2 deaths

Placebo

Serious events: 12 serious events

Other events: 267 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Marisa Russell, Senior Director of Clinical Operations, Clinical Development

IAVI

Phone: +27 21 344 1204

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	H56:IC31 n=415 participants at risk The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=416 participants at risk Sterile saline for injection Placebo: Sterile saline for injection
Injury, poisoning and procedural complications Gun shot wound	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.48% 2/416 • Number of events 2 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Injury, poisoning and procedural complications Chest injury	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Pregnancy, puerperium and perinatal conditions Stillbirth	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Injury, poisoning and procedural complications Stab wound	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Injury, poisoning and procedural complications Toxicity to various agents	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Injury, poisoning and procedural complications Traumatic haemothorax	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Infections and infestations Pneumonia	0.48% 2/415 • Number of events 2 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Infections and infestations Abscess neck	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Infections and infestations Lower respiratory tract infection	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Pregnancy, puerperium and perinatal conditions Abortion incomplete	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Pregnancy, puerperium and perinatal conditions Polyhydramnios	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Cardiac disorders Cor Pulmonale	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Cardiac disorders Supraventricular tachycardia	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Cardiac disorders Tachycardia	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Nervous system disorders Cerebrovascular accident	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Nervous system disorders Epilepsy	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
General disorders Death	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of skin	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Psychiatric disorders Substance-induced psychotic disorder	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/415 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.24% 1/416 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Surgical and medical procedures Hospitalization	0.24% 1/415 • Number of events 1 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	0.00% 0/416 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)

Measure	H56:IC31 n=415 participants at risk The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine. H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique. H56:IC31: 5ug H56/500 nmol IC31	Placebo n=416 participants at risk Sterile saline for injection Placebo: Sterile saline for injection
General disorders Injection site pain	34.0% 141/415 • Number of events 212 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	13.7% 57/416 • Number of events 72 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
General disorders Fatigue	27.0% 112/415 • Number of events 160 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	25.0% 104/416 • Number of events 155 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
General disorders Injection site erythema	18.6% 77/415 • Number of events 98 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	8.7% 36/416 • Number of events 45 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
General disorders Injection site swelling	17.6% 73/415 • Number of events 101 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	5.5% 23/416 • Number of events 27 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
General disorders Pyrexia	6.3% 26/415 • Number of events 31 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	5.5% 23/416 • Number of events 28 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
General disorders Chills	4.8% 20/415 • Number of events 30 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	4.3% 18/416 • Number of events 25 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Musculoskeletal and connective tissue disorders Myalgia	21.9% 91/415 • Number of events 123 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	13.7% 57/416 • Number of events 79 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Musculoskeletal and connective tissue disorders Arthralgia	16.4% 68/415 • Number of events 92 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	14.9% 62/416 • Number of events 83 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Musculoskeletal and connective tissue disorders Back pain	2.9% 12/415 • Number of events 12 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	2.4% 10/416 • Number of events 11 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Nervous system disorders Headache	24.1% 100/415 • Number of events 136 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	25.2% 105/416 • Number of events 158 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Gastrointestinal disorders Nausea	12.8% 53/415 • Number of events 63 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	11.3% 47/416 • Number of events 59 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Gastrointestinal disorders Abdominal pain	2.4% 10/415 • Number of events 12 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	1.9% 8/416 • Number of events 8 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Gastrointestinal disorders Toothache	1.4% 6/415 • Number of events 6 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	2.2% 9/416 • Number of events 9 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Gastrointestinal disorders Diarrhoea	0.96% 4/415 • Number of events 4 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	2.2% 9/416 • Number of events 9 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Infections and infestations Upper respiratory tract infection	4.3% 18/415 • Number of events 18 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	6.0% 25/416 • Number of events 27 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)
Skin and subcutaneous tissue disorders Rash	3.6% 15/415 • Number of events 17 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)	3.4% 14/416 • Number of events 18 • Non-serious solicited and unsolicited adverse events: first 14 days after each vaccination (Day 0 - Day 14; Day 56 - Day 70) Serious adverse events and adverse events of special interest: entire trial period (Day 0 - Day 421)