Trial Outcomes & Findings for The Efficacy and Safety of Cobitolimod (Kappaproct®) in Chronic Active Treatment Refractory Ulcerative Colitis Patients (NCT NCT01493960)

NCT ID: NCT01493960

Last Updated: 2023-01-10

Results Overview

The induction of clinical remission at week 12, defined as a CAI score of ≤4.(Full Analysis Set)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

131 participants

Primary outcome timeframe

Week 12

Results posted on

2023-01-10

Participant Flow

There were 162 subjects screened. Whereof 31 did not meet the criteria

There were131 patients randomly assigned in a 2:1 allocation to receive 2 rectal doses of cobitolimod at 30 mg, or placebo, respectively.

Participant milestones

Participant milestones
Measure	Cobitolimod 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
Overall Study STARTED	87	44
Overall Study Received Study Drug	87	43
Overall Study COMPLETED	55	26
Overall Study NOT COMPLETED	32	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Cobitolimod 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
Overall Study Adverse Event	0	1
Overall Study Lack of Efficacy	15	9
Overall Study Protocol Violation	3	0
Overall Study Withdrawal by Subject	10	4
Overall Study Non-specified	4	4

Baseline Characteristics

The Efficacy and Safety of Cobitolimod (Kappaproct®) in Chronic Active Treatment Refractory Ulcerative Colitis Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4	Total n=124 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	76 Participants n=99 Participants	40 Participants n=107 Participants	116 Participants n=206 Participants
Age, Categorical >=65 years	5 Participants n=99 Participants	3 Participants n=107 Participants	8 Participants n=206 Participants
Age, Continuous	41.1 years STANDARD_DEVIATION 13.88 • n=99 Participants	43.1 years STANDARD_DEVIATION 12.31 • n=107 Participants	41.8 years STANDARD_DEVIATION 13.34 • n=206 Participants
Sex: Female, Male Female	33 Participants n=99 Participants	11 Participants n=107 Participants	44 Participants n=206 Participants
Sex: Female, Male Male	48 Participants n=99 Participants	32 Participants n=107 Participants	80 Participants n=206 Participants
Region of Enrollment Czech Republic	13 participants n=99 Participants	6 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Hungary	13 participants n=99 Participants	6 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Poland	25 participants n=99 Participants	14 participants n=107 Participants	39 participants n=206 Participants
Region of Enrollment Italy	2 participants n=99 Participants	3 participants n=107 Participants	5 participants n=206 Participants
Region of Enrollment United Kingdom	8 participants n=99 Participants	3 participants n=107 Participants	11 participants n=206 Participants
Region of Enrollment Germany	20 participants n=99 Participants	11 participants n=107 Participants	31 participants n=206 Participants
Summary of CAI score at baseline by treatment group	11.1 units on a scale STANDARD_DEVIATION 2.2 • n=99 Participants	10.8 units on a scale STANDARD_DEVIATION 2.1 • n=107 Participants	11.0 units on a scale STANDARD_DEVIATION 2.1 • n=206 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The FAS consited of all randomized patients who met the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and received at least 1 dose of study drug (active or placebo), and who had at least 1 post randomization eligible value of the primary efficacy endpoint

The induction of clinical remission at week 12, defined as a CAI score of ≤4.(Full Analysis Set)

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
Induction of Clinical Remission	44.4 Percentage of participants Interval 34.1 to 55.3	46.5 Percentage of participants Interval 32.5 to 61.1

SECONDARY outcome

Timeframe: Within 12 months

Population: FAS

Median time to colectomy after 1st dose.

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
The Time to Colectomy	NA Time Median was not reached due to few events	NA Time Median was not reached due to few events

SECONDARY outcome

Timeframe: at 12 months

Population: FAS

Percentage of participants undergoing colectomy at 12 months after 1st dose.

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
The Rate of Colectomy	4.9 Percentage of Subjects Interval 1.9 to 12.0	11.6 Percentage of Subjects Interval 5.1 to 24.5

SECONDARY outcome

Timeframe: at 12 months

Population: FAS

Percentage of participants with steroid free remission at 12 months after 1st dose.

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
Steroid Free Remission at 12 Months	32.1 Percentage of Subjects Interval 22.9 to 42.9	30.2 Percentage of Subjects Interval 18.6 to 45.1

SECONDARY outcome

Timeframe: Week 4 and 12

Population: FAS

Percentage of participants with induction of mucosal healing, defined as an endoscopic score of 0 or 1, at week 4 and 12.

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
The Induction of Mucosal Healing Week 4	34.6 Percentage of Subjects Interval 25.1 to 45.4	18.6 Percentage of Subjects Interval 9.7 to 32.6
The Induction of Mucosal Healing Week 12	42.0 Percentage of Subjects Interval 31.8 to 52.8	41.9 Percentage of Subjects Interval 28.4 to 56.7

SECONDARY outcome

Timeframe: Week 4, 12

Population: FAS

Percentage of participants with induction of symptomatic remission, defined as subscores of blood in stool and number of stools weekly not exceeding 0 and 0 or 1, respectively, at week 4 and 12.

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
The Induction of Symptomatic Remission Week 4	32.1 Percentage of Subjects Interval 22.9 to 42.9	14.0 Percentage of Subjects Interval 6.6 to 27.3
The Induction of Symptomatic Remission Week 12	43.2 Percentage of Subjects Interval 33.0 to 54.1	32.6 Percentage of Subjects Interval 20.5 to 47.5

SECONDARY outcome

Timeframe: Week 4 and 12

Population: FAS

Percentage of participants with induction of registration remission, defined as a CAI score of ≤4 and an endoscopic score of 0 or 1, at week 4 and 12.

Outcome measures

Outcome measures
Measure	Cobitolimod n=81 Participants 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 Participants 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
The Induction of Registration Remission Week 4	21.0 Percentage of Subjects Interval 13.5 to 31.1	4.7 Percentage of Subjects Interval 1.3 to 15.5
The Induction of Registration Remission Week 12	30.9 Percentage of Subjects Interval 21.9 to 41.6	30.2 Percentage of Subjects Interval 18.6 to 45.1

Adverse Events

Cobitolimod

Serious events: 10 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Cobitolimod n=87 participants at risk 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 participants at risk 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
Blood and lymphatic system disorders Anemia	4.6% 4/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Endocrine disorders Cushingoid	4.6% 4/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Gastrointestinal disorders Abdominal Pain	3.4% 3/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Infections and infestations Nasopharyngitis	5.7% 5/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Musculoskeletal and connective tissue disorders Back Pain	3.4% 3/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Nervous system disorders Headache	5.7% 5/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	4.7% 2/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Psychiatric disorders Depression	3.4% 3/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Skin and subcutaneous tissue disorders Rash	4.6% 4/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.

Additional Information

Dr Thomas Knittel

Index Pharmaceuticals

Phone: 0046 8 508 847 31

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cobitolimod n=87 participants at risk 2 doses 4 weeks apart Cobitolimod: 30 mg rectal dose at week 0 and 4	Placebo n=43 participants at risk 2 doses 4 weeks apart Placebo: Rectal dose at week 0 and 4
Blood and lymphatic system disorders Anemia	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Cardiac disorders Acute Coronary syndrome	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Cardiac disorders Myocardial Ischemia	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Eye disorders Glaucoma	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Eye disorders Retinal Veon Thrombosis	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Gastrointestinal disorders Perirectal abscess	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Infections and infestations Herpes Zoster	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Reproductive system and breast disorders Clostridial infection	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Gastrointestinal disorders Vomiting	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Injury, poisoning and procedural complications Overdose	2.3% 2/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Musculoskeletal and connective tissue disorders Spinal compression fracture	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Nervous system disorders Sensory Distrurbance	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Nervous system disorders Movement disorder	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Reproductive system and breast disorders Benign Dysplaisa	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	2.3% 1/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Skin and subcutaneous tissue disorders Rash	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.
Vascular disorders Epistaxis	1.1% 1/87 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.	0.00% 0/43 • 1 year, 2 weeks All patients who entered into the study and were treated with at least 1 dose of study drug are included in the safety analysis set.