Trial Outcomes & Findings for Phase IIb Study of IFN-K in Systemic Lupus Erythematosus (NCT NCT02665364)

Last Updated: 2020-04-09

Results Overview

The biological endpoint aimed at evaluating the neutralization of the IFN gene signature following treatment with IFN-K compared to placebo, as measured by the % change from baseline of the expression of IFN-induced genes.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

185 participants

Primary outcome timeframe

Baseline and Last Available Value (LVA) between week 24 and week 36

Results posted on

2020-04-09

Participant Flow

The number of participants enrolled is the number of participants who signed informed condent form. One subject was randomized in IFN-K group and did not receive IFN-K. A total of 185 subjects were randomized and 184 subjects were treated : 91 subjects received IFN-K and 93 subjects received placebo.

Participant milestones

Participant milestones
Measure	IFN-K Subjects received IFN-K adjuvanted with ISA 51 VG via intramuscular injection. 1 administration of 240 μg at W0, W1, W4 and 1 administration of 120 μg at month 3 (W12) and month 6 (W24) in addition to standard of care treatment.	Placebo Subjects received placebo normal saline (0.9% Sodium Chloride) adjuvanted with ISA 51 VG via intramuscular injection. 1 administration of 240 μg at week (W)0, W1, W4 and 1 administration of 120 μg at month 3 (W12) and month 6 (W24) in addition to standard of care treatment.
Overall Study STARTED	91	93
Overall Study COMPLETED	85	84
Overall Study NOT COMPLETED	6	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase IIb Study of IFN-K in Systemic Lupus Erythematosus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IFN-Kinoid n=91 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=93 Participants Placebo adjuvanted with ISA 51 VG	Total n=184 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Age, Categorical Between 18 and 65 years	91 Participants n=39 Participants	93 Participants n=41 Participants	184 Participants n=35 Participants
Age, Categorical >=65 years	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Sex: Female, Male Female	84 Participants n=39 Participants	88 Participants n=41 Participants	172 Participants n=35 Participants
Sex: Female, Male Male	7 Participants n=39 Participants	5 Participants n=41 Participants	12 Participants n=35 Participants
Race/Ethnicity, Customized Eyhnic origin · Black	1 Participants n=39 Participants	1 Participants n=41 Participants	2 Participants n=35 Participants
Race/Ethnicity, Customized Eyhnic origin · Asian	16 Participants n=39 Participants	10 Participants n=41 Participants	26 Participants n=35 Participants
Race/Ethnicity, Customized Eyhnic origin · Caucasian/Hispanic	68 Participants n=39 Participants	72 Participants n=41 Participants	140 Participants n=35 Participants
Race/Ethnicity, Customized Eyhnic origin · Other	6 Participants n=39 Participants	10 Participants n=41 Participants	16 Participants n=35 Participants
Region of Enrollment Colombia	9 participants n=39 Participants	9 participants n=41 Participants	18 participants n=35 Participants
Region of Enrollment United States	2 participants n=39 Participants	4 participants n=41 Participants	6 participants n=35 Participants
Region of Enrollment Philippines	10 participants n=39 Participants	9 participants n=41 Participants	19 participants n=35 Participants
Region of Enrollment Moldova	6 participants n=39 Participants	14 participants n=41 Participants	20 participants n=35 Participants
Region of Enrollment Thailand	3 participants n=39 Participants	0 participants n=41 Participants	3 participants n=35 Participants
Region of Enrollment Russia	9 participants n=39 Participants	13 participants n=41 Participants	22 participants n=35 Participants
Region of Enrollment South Korea	1 participants n=39 Participants	0 participants n=41 Participants	1 participants n=35 Participants
Region of Enrollment Belgium	1 participants n=39 Participants	0 participants n=41 Participants	1 participants n=35 Participants
Region of Enrollment Taiwan	1 participants n=39 Participants	1 participants n=41 Participants	2 participants n=35 Participants
Region of Enrollment Poland	13 participants n=39 Participants	5 participants n=41 Participants	18 participants n=35 Participants
Region of Enrollment Italy	3 participants n=39 Participants	3 participants n=41 Participants	6 participants n=35 Participants
Region of Enrollment Mexico	10 participants n=39 Participants	9 participants n=41 Participants	19 participants n=35 Participants
Region of Enrollment Georgia	2 participants n=39 Participants	3 participants n=41 Participants	5 participants n=35 Participants
Region of Enrollment France	1 participants n=39 Participants	0 participants n=41 Participants	1 participants n=35 Participants
Region of Enrollment Chile	2 participants n=39 Participants	4 participants n=41 Participants	6 participants n=35 Participants
Region of Enrollment Peru	10 participants n=39 Participants	11 participants n=41 Participants	21 participants n=35 Participants
Region of Enrollment Germany	2 participants n=39 Participants	2 participants n=41 Participants	4 participants n=35 Participants
Region of Enrollment Croatia	1 participants n=39 Participants	1 participants n=41 Participants	2 participants n=35 Participants
Region of Enrollment Argentina	0 participants n=39 Participants	1 participants n=41 Participants	1 participants n=35 Participants
Region of Enrollment Tunisia	5 participants n=39 Participants	4 participants n=41 Participants	9 participants n=35 Participants

PRIMARY outcome

Timeframe: Baseline and Last Available Value (LVA) between week 24 and week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 87 had a Last available value (LAV) between Week 24 and Week 36 analyzed. 93 subjects received placebo, among them, 84 had LAV between Week 24 and Week 36 analyzed.

Outcome measures

Outcome measures
Measure	IFN-K n=87 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=84 Participants Placebo adjuvanted with ISA 51 VG
Percent Change From Baseline in IFN Gene Signature at W36	-31.04 percent change Standard Deviation 38.96	-0.44 percent change Standard Deviation 27.34

PRIMARY outcome

Timeframe: At Week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 85 completed Week 36 visit. 93 subjects received placebo, among them, 84 completed Week 36 visit.

British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responder was defined as a subject who had the following criteria at week 36: * All BILAG A scores at baseline improve to B/C/D and all BILAG B scores improve to C/D at W36, and * No BILAG worsening in other body systems: no new BILAG A or ≥ 2 new BILAG B scores at W36, and * No worsening in SLEDAI-2K total score at W36 compared with baseline, and * No deterioration in Physician Global Assessment (PGA) (\< 10% worsening) on Visual Analog Scale (VAS) 100 mm at W36 compared with baseline, and * No addition or increased dose level of anti-malarial drugs or immunosuppressive drugs or CS\* between W24 and W36 (\*≤5 mg prednisolone or equivalent /day at W24 and no increase until W36).

Outcome measures

Outcome measures
Measure	IFN-K n=85 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=84 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering at Week 36	35 Participants	29 Participants

SECONDARY outcome

Timeframe: W36 (9 months)

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 84 completed Week 36 visit. 93 subjects received placebo, among them, 83 completed Week 36 visit.

SLE Responder Index (SRI); SRI-4 responder was defined as a subject who had the following criteria at week 36: * reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and * no new BILAG A at week 36, and * no more than 1 new BILAG B at week 36, and * no deterioration in PGA (\<10% worsening) on 100-mm VAS compared with baseline

Outcome measures

Outcome measures
Measure	IFN-K n=84 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=83 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36	57 Participants	54 Participants

SECONDARY outcome

Timeframe: At Week 36

Lupus low disease activity state (LLDAS) was conceptually defined as 'a state which, if sustained, is associated with a low likelihood of adverse outcome, considering disease activity and medication safety'. Subsequently defined using consensus methodology, LLDAS is attained if all the following items are met: * SLEDAI-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity * No new features of lupus disease activity compared with the previous assessment * SELENA-SLEDAI physician global assessment (PGA, scale 0-3) ≤1 * Current prednisolone (or equivalent) dose ≤7.5 mg daily * Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs

Outcome measures

Outcome measures
Measure	IFN-K n=85 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=84 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) at Week 36	45 Participants	25 Participants

SECONDARY outcome

Timeframe: Last Available Value (LVA) between week 24 and week 36

British Isles Lupus Assessment Group (BILAG)-2004 index, it categorizes disease activity into 5 different levels from A to E, with Grade A representing very active disease and Grade E indicating no current or previous disease activity. Scoring was based on a total of 101 items, grouped into 9 organ/systems and the summation of the numerical values for the nine-system scores was given by the following formula: Numerical global score = A\*12 + B\*8 + C\*1, where A, B and C represent the number of Grades A, B and C respectively at each assessment. Grades D and E are considered as 0 (Chee-Seng Yee et al, 2010). The minimum score is 0 with no predefined maximum. The higher scores mean a worse outcome. The BILAG global score change from baseline to Last Available Value (LVA) week 24 and week 36 were presented analyzed.

Outcome measures

Outcome measures
Measure	IFN-K n=87 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=84 Participants Placebo adjuvanted with ISA 51 VG
BILAG Global Score Change From Baseline to Last Available Value (LVA) Between Week 24 and Week 36	-11.43 scores on a scale Standard Deviation 8.57	-10.76 scores on a scale Standard Deviation 7.84

SECONDARY outcome

Timeframe: Baseline and Week 36

Safety of Estrogens in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI, is a slightly modified version of the SLEDAI. This is a weighted index in which signs and symptoms, laboratory tests, and Physician's Global Assessment (PGA) for each of nine organ systems are given a weighted score and summed up if present at the time of the visit or in the preceding 10 days. The maximum theoretical score for the SELENA SLEDAI is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease.

Outcome measures

Outcome measures
Measure	IFN-K n=84 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=83 Participants Placebo adjuvanted with ISA 51 VG
SELENA-SLEDAI - Change From Baseline to Week 36	-5.48 SELENA SLEDAI Score Standard Deviation 4.30	-5.54 SELENA SLEDAI Score Standard Deviation 4.44

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 82 completed SLICC/ACR/DI questionnaire at Week 36 visit. 93 subjects received placebo, among them, 83 completed Week 36 visit.

Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus (SLICC/ACR-DI) captures permanent changes which have occurred in patients with SLE, regardless of causality. The questionnaire contains 41 items covering 12 different organ systems. The score of items ranges from 1 to 3 and the total score from 0 to 47. By definition score 0 corresponds to diagnostics and damage over time can only be stable or increase, theoretically to a maximum of 47 points.

Outcome measures

Outcome measures
Measure	IFN-K n=82 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=83 Participants Placebo adjuvanted with ISA 51 VG
SLICC/ACR-DI Change From Baseline at Week 36	-0.09 scores on a scale Standard Deviation 0.59	-0.17 scores on a scale Standard Deviation 0.49

SECONDARY outcome

Timeframe: Baseline and Week 36

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was specifically developed to assess the cutaneous manifestations of SLE. It measures both disease activity and permanent damage (e.g. dyspigmentation and scarring) over the entire body surface. CLASI total activity score ranges from 0 to 70, with higher scores indicating more severe skin disease.

Outcome measures

Outcome measures
Measure	IFN-K n=85 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=84 Participants Placebo adjuvanted with ISA 51 VG
CLASI Total Activity Change From Baseline at Week 36	-3.22 scores on a scale Standard Deviation 5.94	-2.85 scores on a scale Standard Deviation 3.60

SECONDARY outcome

Timeframe: At Week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 79 had CS ≤7,5mg/day at Week 36 visit. 93 subjects received placebo, among them, 77 had CS ≤7,5mg/day at Week 36 visit.

SRI (4) plus CS ≤ 7.5 mg/day responder was defined as a participant who had the following criteria at week 36: * reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and * no new BILAG A at week 36, and * no more than 1 new BILAG B at week 36, and * no deterioration in PGA (\<10% worsening) on 100-mm VAS compared with baseline plus CS ≤7.5mg equivalent prednisolone per day at week 36

Outcome measures

Outcome measures
Measure	IFN-K n=79 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=77 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a Composite SRI-4 Including CS ≤7,5mg/Day at Week 36	46 Participants	33 Participants

SECONDARY outcome

Timeframe: At Week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 79 had CS ≤5mg/day at Week 36 visit. 93 subjects received placebo, among them, 77 had CS ≤5mg/day at Week 36 visit.

SRI-4 plus CS ≤ 5mg/day responder was defined as a participant who had the following criteria at Week 36: * reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and * no new BILAG A at week 36, and * no more than 1 new BILAG B at week 36, and * no deterioration in PGA (\<10% worsening) on 100-mm VAS compared with baseline plus corticosteroids (CS) ≤5mg equivalent prednisolone per day at week 36

Outcome measures

Outcome measures
Measure	IFN-K n=79 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=77 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a Composite SRI-4 Including CS ≤5mg/Day at Week 36	43 Participants	30 Participants

SECONDARY outcome

Timeframe: At week 36

Population: 91 subjects received IFN-K, among them, 79 were positive for Anti-IFN-alpha antibodies at Week 36 visit. No Neutralizing Anti-IFN-alpha antibodies were performed on placebo subjects.

Individual serum antibody neutralizing capacity against recombinant IFN-alpha2b was measured by reporter gene assay using Interferon Sensitive Response Element (ISRE) reporter.

Outcome measures

Outcome measures
Measure	IFN-K n=79 Participants IFN-K adjuvanted with ISA 51 VG	Placebo Placebo adjuvanted with ISA 51 VG
Number of Participants With Neutralizing Anti-IFN-alpha Antibodies at W36	72 Participants	0 Participants

SECONDARY outcome

Timeframe: 9 months

Number of participants who reported any treatment-related adverse events until month 9

Outcome measures

Outcome measures
Measure	IFN-K n=91 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=93 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants With Treatment-related Adverse Events	75 Participants	71 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At W36

mean daily dose of corticosteroid (CS) (prednisone equivalent)

Outcome measures

Outcome measures
Measure	IFN-K n=85 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=84 Participants Placebo adjuvanted with ISA 51 VG
CS Mean Daily Dose at W36	5.42 mg/day Standard Error 3.28	7.06 mg/day Standard Error 4.69

POST_HOC outcome

Timeframe: At week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 72 had a Composite SRI-4 (CS ≤5mg/day) at Week 36 visit. 93 subjects received placebo, among them, 77 had a Composite SRI-4 CS ≤5mg/day at Week 36 visit.

Subjects who had the following criteria defined as : SRI-4 plus CS ≤5mg/day -excluding IFN-K subjects without positive anti-IFN-alpha neutralizing antibodies

Outcome measures

Outcome measures
Measure	IFN-K n=72 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=77 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a Composite SRI-4 (CS ≤5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36	40 Participants	30 Participants

POST_HOC outcome

Timeframe: At week 36

Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 72 had a Composite SRI-4 (CS ≤7.5mg/day) at Week 36 visit. 93 subjects received placebo, among them, 77 had a Composite SRI-4 (CS ≤7.5mg/day) at Week 36 visit.

participant who had the following criteria defined as : SRI-4 plus CS ≤7.5mg/day -excluding IFN-K Patients without positive anti-IFN-alpha neutralizing antibodies

Outcome measures

Outcome measures
Measure	IFN-K n=72 Participants IFN-K adjuvanted with ISA 51 VG	Placebo n=77 Participants Placebo adjuvanted with ISA 51 VG
Number of Participants Who Achieved a Composite SRI-4 (CS ≤7.5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36	43 Participants	33 Participants

Adverse Events

IFN-K

Serious events: 6 serious events

Other events: 75 other events

Deaths: 1 deaths

Placebo

Serious events: 12 serious events

Other events: 71 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Regulatory Affairs

Neovacs

Phone: +33153109300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	IFN-K n=91 participants at risk IFN-K adjuvanted with ISA 51 VG	Placebo n=93 participants at risk Placebo adjuvanted with ISA 51 VG
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	2.2% 2/93 • Number of events 2 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Immune system disorders Systemic lupus erythematosus	2.2% 2/91 • Number of events 3 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	3.2% 3/93 • Number of events 3 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Immune system disorders Lupus Nephritis	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Immune system disorders Neuropsychiatric Lupus	1.1% 1/91 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Central nervous system lymphoma	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer stage II	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Blood and lymphatic system disorders Haemolytic anaemia	1.1% 1/91 • Number of events 2 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Gastrointestinal disorders Diarrhoea	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Gastrointestinal disorders Pancreatitis	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
General disorders chest pain	1.1% 1/91 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
General disorders Disease progression	1.1% 1/91 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Respiratory, thoracic and mediastinal disorders Acute respiratory faillure	1.1% 1/91 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Respiratory, thoracic and mediastinal disorders pleural effusion	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Renal and urinary disorders Renal colic	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Reproductive system and breast disorders Postmenauposal haemorrhage	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Infections and infestations Pneumonia	2.2% 2/91 • Number of events 2 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Infections and infestations Kaposi's varicelliform eruption	1.1% 1/91 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Infections and infestations Urinary tract infection	1.1% 1/91 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	0.00% 0/93 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.
Infections and infestations Viral infection	0.00% 0/91 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.	1.1% 1/93 • Number of events 1 • Adverse Events (AEs) non serious and serious (SAEs) were collected from the start of study Investigational Medicinal Product (IMP) to Week 36. Due to IFN-K mechanism of action, i.e. immunization, and the administration route, i.e. intramuscular (IM), some AEs, local and/or systemic AEs, were expected and solicited within 7 days after study Investigational Medicinal Product (IMP) administration.