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

Phase 2

• Conditions: Ulcerative Colitis
• Interventions: Drug: OSE-127; Drug: Placebo

• Registration Number: NCT04882007
• Lead Sponsor: OSE Immunotherapeutics

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-02
• Study First Submitted: 2021-04-13
• Study First Submitted QC: 2021-05-08
• Study First Posted: 2021-05-11
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-25
• Last Update Posted: 2021-06-28
• Primary Completion: 2021-12
• Study Completion: 2023-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. 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

2. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

3. Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose

4. Male or female 18 to 75 years of age, inclusive

5. 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:

   1. a rectal bleeding score ≥ 1,
   2. a stool frequency score ≥ 1 (sub-score calculated before bowel preparation), and
   3. an endoscopic sub-score ≥ 2

6. 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:

   1. Corticosteroids
   2. Immunosuppressive agents

OR

Previous or current biologic therapy

Exclusion Criteria

1. Stoma, proctocolectomy, or subtotal colectomy

2. Physician judgment that patient is likely to require any surgery for UC during the study duration, or double-blind phase duration at least

3. Evidence of fulminant colitis, toxic megacolon, or perforation

4. Current or recent (within 4 weeks prior to screening) hospitalization for UC care and/or treatment with IV steroids

5. The following laboratory results at screening:

   1. 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
   2. Platelet count < 100,000/mm3
   3. Hemoglobin (Hgb) < 8.5 g/dL
   4. Neutrophils < 1500/mm3
   5. Lymphocytes < 800/mm3
   6. Absolute white blood cell (WBC) count < 3000/mm3

6. Crohn's disease or indeterminate colitis or any other diagnosis not consisting with UC

7. History or evidence of incompletely resected colonic dysplasia or unconventional lesion at risk of colonic adenocarcinoma

8. 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.

9. 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.

10. Breastfeeding

11. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) from screening through the end of the study

12. 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)

13. 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)

14. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	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

Trial Locations

Locations (55)

Ekaterinburg City Clinical Hospital No. 14; 🇷🇺 Ekaterinburg, Russian Federation

Groupe Santé CHC - Clinique du Mont Légia; 🇧🇪 Liège, Belgium

Medical Center Medconsult Pleven - OOD; 🇧🇬 Pleven, Bulgaria

Prof. O.O. Salimov City Clinical Hospital #2 - Kharkiv City Council; 🇺🇦 Kharkiv, Ukraine

Kyiv Regional Clinical Hospital - Kyiv Regional Council; 🇺🇦 Kyiv, Ukraine

Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital - Dnipropetrovsk Regional Council; 🇺🇦 Dnipro, Ukraine

Ternopil University Hospital - Ternopil Regional Council; 🇺🇦 Ternopil, Ukraine

Andrii Novak Transcarpathian Regional Clinical Hospital; 🇺🇦 Uzhhorod, Ukraine

Clinexpert SMO; 🇭🇺 Budapest, Hungary

Ryzhikh State Coloproctology Research Center; 🇷🇺 Moscow, Russian Federation

LLC Novosibirskiy Gastrocenter; 🇷🇺 Novosibirsk, Russian Federation

301 Fairfield Medical Suite; 🇿🇦 Cape Town, South Africa

Saratov State Medical University; 🇷🇺 Saratov, Russian Federation

Medical Center OK!Clinic+ of International Institute of Clinical Studies LLC; 🇺🇦 Kyiv, Ukraine

Gomel Regional Clinical Hospital; 🇧🇾 Gomel, Belarus

Brest Regional Hospital; 🇧🇾 Brest, Belarus

City Clinical Emergency Hospital; 🇧🇾 Minsk, Belarus

Grodno University Hospital; 🇧🇾 Grodno, Belarus

UZ Leuven - Department of Gastroenterology and Hepatology; 🇧🇪 Leuven, Belgium

Vitebsk Regional Clinical Hospital; 🇧🇾 Vitebsk, Belarus

CHU Liège; 🇧🇪 Liège, Belgium

Medical Center VIP Clinic; 🇧🇬 Varna, Bulgaria

Medical Center Medconsult Pleven; 🇧🇬 Pleven, Bulgaria

Acibadem City Clinic University Multiprofile Hospital for Active Treatment - EOOD, Clinic of Gastroenterology; 🇧🇬 Sofia, Bulgaria

Medical Center Asklepion - Researches in humane medicine (EOOD); 🇧🇬 Sofia, Bulgaria

Medical Center Hera EOOD; 🇧🇬 Sofia, Bulgaria

Medical Center Asklepion; 🇧🇬 Sofia, Bulgaria

UMHAT Tsaritsa Yoanna - ISUL - EAD; 🇧🇬 Sofia, Bulgaria

Medical Center Hera; 🇧🇬 Sofia, Bulgaria

Medical center VIP Clinic - OOD; 🇧🇬 Varna, Bulgaria

West Regional Center of Modern Medical Technologies Ltd; 🇬🇪 Kutaisi, Georgia

EVEX Hospitals JSC; 🇬🇪 Kutaisi, Georgia

University Hospital Center Split; 🇭🇷 Split, Croatia

Institute of Clinical Cardiology; 🇬🇪 Tbilisi, Georgia

Israel-Georgia Medical Research Clinic Helsicore Ltd; 🇬🇪 Tbilisi, Georgia

Multiprofile Clinic Consilium Medulla Ltd; 🇬🇪 Tbilisi, Georgia

JSC Clinic Jerarsi; 🇬🇪 Tbilisi, Georgia

II. Sz. Belgyogyaszati Klinika, Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

II. Sz Belgyogyasztai Intezet, Gasztroenterologia Debreceni Egyetem; 🇭🇺 Debrecen, Hungary

Polana-D; 🇱🇻 Daugavpils, Latvia

Digestive Diseases Centre GASTRO; 🇱🇻 Riga, Latvia

Liepāja Regional Hospital; 🇱🇻 Liepāja, Latvia

Medicome Sp. z o.o.; 🇵🇱 Oświęcim, Poland

Pauls Stradins Clinical University Hospital; 🇱🇻 Riga, Latvia

Centrum Opieki Zdrowotnej Orkan-med; 🇵🇱 Ksawerów, Poland

Centrum Medyczne Medyk; 🇵🇱 Rzeszów, Poland

WIP Warsaw IBD Point Profesor Kierkus; 🇵🇱 Warszawa, Poland

Melita Medical; 🇵🇱 Wrocław, Poland

Centrum Medyczne Med-Gastr; 🇵🇱 Łódź, Poland

Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej; 🇵🇱 Łódź, Poland

Prof. S.V. Ochapovskiy Regional Clinical Hospital No.1; 🇷🇺 Krasnodar, Russian Federation

State Budgetary Healthcare Institution of the Stavropol Region - Pyatigorsk Oncology Dispensary; 🇷🇺 Pyatigorsk, Russian Federation

Medical Center Healthy Family LLC; 🇷🇺 Novosibirsk, Russian Federation

Kryvyi Rih City Clinical Hospital #2; 🇺🇦 Kryvyi Rih, Ukraine

Municipal Institution City Clinical Hospital #6 - Therapeutic Department; 🇺🇦 Zaporizhzhya, Ukraine