CoTikiS: Study of OSE-127 vs Placebo in Patients With Moderate to Severe Active Ulcerative Colitis

Sponsor

OSE Immunotherapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04882007

Collaborator

(none)

150

Enrollment

Locations

Arms

28.9

Anticipated Duration (Months)

2.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in patients with moderate to severe active ulcerative colitis.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: OSE-127 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

During the Double-blind phase all participants will be blinded to treatment assignment.

Primary Purpose:

Treatment

Official Title:

Randomized, Double-blind, Phase 2 Study to Evaluate the Efficacy and the Safety of OSE-127 Versus Placebo in Subjects With Moderate to Severe Active Ulcerative Colitis Who Have Failed or Are Intolerant to Previous Treatment(s)

Actual Study Start Date :

Oct 2, 2020

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OSE-127 High dose induction phase OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα) intravenous infusion 3 total infusions, weeks 0, 2, and 6	Drug: OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα)
Experimental: OSE-127 Low dose induction phase OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα) intravenous infusion 3 total infusions, weeks 0, 2, and 6	Drug: OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα)
Placebo Comparator: Placebo induction phase Normal saline intravenous infusion 3 total infusions, weeks 0, 2, and 6	Drug: Placebo Normal saline
Experimental: OSE-127 High dose optional extension phase OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα) intravenous infusion 7 total infusions, weeks 10, 14, 18, 22, 26, 30, and 34	Drug: OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα)

Outcome Measures

Primary Outcome Measures

Change in modified Mayo Score [Baseline and Week 10]
Change in modified Mayo Score between baseline and Week 10 clinical symptoms (stool frequency and rectal bleeding sub-scores) additionally to the endoscopic sub-score

Secondary Outcome Measures

Clinical Remission [Week 10]
Number and proportion of patients achieving clinical remission at Week 10, defined as a modified Mayo score of ≤ 2 points and with no individual sub-score of > 1 point and a rectal bleeding at 0, therefore a stool frequency score of 0 or 1 and an endoscopic score of 0 or 1
Clinical efficacy of OSE-127 vs placebo [Week 10]
Number and proportion of patients with a clinical response defined as a reduction in the modified Mayo score of ≥ 3 points and of ≥ 30% from baseline, with an accompanying decrease from baseline in the rectal bleeding sub-score of ≥ 1 point or an absolute rectal bleeding sub-score of ≤ 1 point
Efficacy of OSE-127 vs placebo on endoscopic remission [Week 10]
Number and proportion of patients with an endoscopic remission defined by an endoscopic Mayo sub-score =0
Efficacy of OSE-127 vs placebo on endoscopic improvement [Week 10]
Number and proportion of patients with endoscopic response or improvement defined by an endoscopic subscore of Mayo ≤ 1 point
Efficacy of OSE-127 vs placebo on endoscopic improvement [Week 10]
Mean change from baseline in the endoscopic activity measured by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Overall safety and tolerability of OSE-127 in patients with moderate to severe UC [Week 0 to Week 22 for patients not participating in the optional extension, and Week 0 to Week 50 for patients participating in the optional extension]
Frequency and severity of reported treatment-emergent adverse events, serious adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose
Male or female 18 to 75 years of age, inclusive
Diagnosis of moderate to severe active UC made at least 3 months before the screening visit. The diagnosis of UC must have been confirmed by endoscopy, with a minimal extent of 15 cm from anal margin and histology (Moderate to severe active UC is defined by a modified Mayo score between 4 and 9, inclusive. The modified Mayo score is defined by the addition of the rectal bleeding subscore, the stool frequency sub-score, and the endoscopic sub-score. Thus, to be included, a patient must have the following:
a rectal bleeding score ≥ 1,
a stool frequency score ≥ 1 (sub-score calculated before bowel preparation), and
an endoscopic sub-score ≥ 2
No previous biologic therapy (i.e., TNF antagonists, vedolizumab or ustekinumab) and prior or current UC documented medication history that includes at least 1 of the following:
Corticosteroids
Immunosuppressive agents

Previous or current biologic therapy

Exclusion Criteria:

Stoma, proctocolectomy, or subtotal colectomy
Physician judgment that patient is likely to require any surgery for UC during the study duration, or double-blind phase duration at least
Evidence of fulminant colitis, toxic megacolon, or perforation
Current or recent (within 4 weeks prior to screening) hospitalization for UC care and/or treatment with IV steroids
The following laboratory results at screening:
Elevation at screening of aminotransferase (AST), alanine aminotransferase (ALT)

3 × the upper limit of normal (ULN) or total bilirubin > 2 × ULN (unless due to Gilbert's disease) or evidence of chronic liver disease

Platelet count < 100,000/mm3
Hemoglobin (Hgb) < 8.5 g/dL
Neutrophils < 1500/mm3
Lymphocytes < 800/mm3
Absolute white blood cell (WBC) count < 3000/mm3
Crohn's disease or indeterminate colitis or any other diagnosis not consisting with UC
History or evidence of incompletely resected colonic dysplasia or unconventional lesion at risk of colonic adenocarcinoma
Stool culture or other examination positive for enteric pathogen, including Clostridium difficile (C. diff) toxin. If positive, the patient should be treated and rescreening is allowed.
Men or women with childbearing potential not willing to use adequate birth control during the study. Adequate birth control includes surgical sterilization, intrauterine device, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy, double-barrier method (condom, diaphragm with spermicide), or abstinence during study and 30 days following the last follow-up visit. Women of childbearing potential will enter the study after a negative pregnancy test.
Breastfeeding
Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) from screening through the end of the study
Use of topical steroids and/or topical 5-aminosalicylic acid preparations within 2 weeks before the screening visit (all such medications should be withdrawn at least 2 weeks prior to the screening visit)
Use of antidiarrheals within 2 weeks before the screening visit (all such medications should be withdrawn at least 2 weeks prior to the screening visit)
Treatment with azathioprine, 6-MP, methotrexate (MTX), cyclosporin, tacrolimus, sirolimus, leflunomide and/or mycophenolate mofetil within 4 weeks before the screening visit (all such medications should be withdrawn at least 4 weeks prior to the screening visit)

Contacts and Locations

Locations

	Site	City	Country
1	Brest Regional Hospital	Brest	Belarus
2	Gomel Regional Clinical Hospital	Gomel	Belarus
3	Grodno University Hospital	Grodno	Belarus
4	City Clinical Emergency Hospital	Minsk	Belarus
5	Vitebsk Regional Clinical Hospital	Vitebsk	Belarus
6	UZ Leuven - Department of Gastroenterology and Hepatology	Leuven	Belgium
7	CHU Liège	Liège	Belgium
8	Groupe Santé CHC - Clinique du Mont Légia	Liège	Belgium
9	Medical Center Medconsult Pleven - OOD	Pleven	Bulgaria
10	Medical Center Medconsult Pleven	Pleven	Bulgaria
11	Acibadem City Clinic University Multiprofile Hospital for Active Treatment - EOOD, Clinic of Gastroenterology	Sofia	Bulgaria
12	Medical Center Asklepion - Researches in humane medicine (EOOD)	Sofia	Bulgaria
13	Medical Center Asklepion	Sofia	Bulgaria
14	Medical Center Hera EOOD	Sofia	Bulgaria
15	Medical Center Hera	Sofia	Bulgaria
16	UMHAT Tsaritsa Yoanna - ISUL - EAD	Sofia	Bulgaria
17	Medical center VIP Clinic - OOD	Varna	Bulgaria
18	Medical Center VIP Clinic	Varna	Bulgaria
19	University Hospital Center Split	Split	Croatia
20	EVEX Hospitals JSC	Kutaisi	Georgia
21	West Regional Center of Modern Medical Technologies Ltd	Kutaisi	Georgia
22	Institute of Clinical Cardiology	Tbilisi	Georgia
23	Israel-Georgia Medical Research Clinic Helsicore Ltd	Tbilisi	Georgia
24	JSC Clinic Jerarsi	Tbilisi	Georgia
25	Multiprofile Clinic Consilium Medulla Ltd	Tbilisi	Georgia
26	Clinexpert SMO	Budapest	Hungary
27	II. Sz. Belgyogyaszati Klinika, Semmelweis Egyetem	Budapest	Hungary
28	II. Sz Belgyogyasztai Intezet, Gasztroenterologia Debreceni Egyetem	Debrecen	Hungary
29	Polana-D	Daugavpils	Latvia
30	Liepāja Regional Hospital	Liepāja	Latvia
31	Digestive Diseases Centre GASTRO	Riga	Latvia
32	Pauls Stradins Clinical University Hospital	Riga	Latvia
33	Centrum Opieki Zdrowotnej Orkan-med	Ksawerów	Poland
34	Medicome Sp. z o.o.	Oświęcim	Poland
35	Centrum Medyczne Medyk	Rzeszów	Poland
36	WIP Warsaw IBD Point Profesor Kierkus	Warszawa	Poland
37	Melita Medical	Wrocław	Poland
38	Centrum Medyczne Med-Gastr	Łódź	Poland
39	Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej	Łódź	Poland
40	Ekaterinburg City Clinical Hospital No. 14	Ekaterinburg	Russian Federation
41	Prof. S.V. Ochapovskiy Regional Clinical Hospital No.1	Krasnodar	Russian Federation
42	Ryzhikh State Coloproctology Research Center	Moscow	Russian Federation
43	LLC Novosibirskiy Gastrocenter	Novosibirsk	Russian Federation
44	Medical Center Healthy Family LLC	Novosibirsk	Russian Federation
45	State Budgetary Healthcare Institution of the Stavropol Region - Pyatigorsk Oncology Dispensary	Pyatigorsk	Russian Federation
46	Saratov State Medical University	Saratov	Russian Federation
47	301 Fairfield Medical Suite	Cape Town	South Africa
48	Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital - Dnipropetrovsk Regional Council	Dnipro	Ukraine
49	Prof. O.O. Salimov City Clinical Hospital #2 - Kharkiv City Council	Kharkiv	Ukraine
50	Kryvyi Rih City Clinical Hospital #2	Kryvyi Rih	Ukraine
51	Kyiv Regional Clinical Hospital - Kyiv Regional Council	Kyiv	Ukraine
52	Medical Center OK!Clinic+ of International Institute of Clinical Studies LLC	Kyiv	Ukraine
53	Ternopil University Hospital - Ternopil Regional Council	Ternopil	Ukraine
54	Andrii Novak Transcarpathian Regional Clinical Hospital	Uzhhorod	Ukraine
55	Municipal Institution City Clinical Hospital #6 - Therapeutic Department	Zaporizhzhya	Ukraine