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

Ulcerative Colitis Clinical Trial

— CoTikiS  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04882007
• Other study ID #: OSE-127-C201
• Secondary ID: 2020-001398-59
• Status: Recruiting
• Phase: Phase 2
• Start date: October 2, 2020
• Est. completion date: March 2023

Study information

• Verified date: June 2021
• Source: OSE Immunotherapeutics
• Contact: Caroline Chevalier
• Phone: +33 630 842 002
• Email: caroline.chevalier[@]ose-immuno.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: March 2023
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• OSE-127
mAb antagonist to CD127 receptor (or IL-7Ra)
• Placebo
Normal saline

Locations

Country	Name	City	State
Belarus	Brest Regional Hospital	Brest
Belarus	Gomel Regional Clinical Hospital	Gomel
Belarus	Grodno University Hospital	Grodno
Belarus	City Clinical Emergency Hospital	Minsk
Belarus	Vitebsk Regional Clinical Hospital	Vitebsk
Belgium	UZ Leuven - Department of Gastroenterology and Hepatology	Leuven
Belgium	CHU Liège	Liège
Belgium	Groupe Santé CHC - Clinique du Mont Légia	Liège
Bulgaria	Medical Center Medconsult Pleven	Pleven
Bulgaria	Medical Center Medconsult Pleven - OOD	Pleven
Bulgaria	Acibadem City Clinic University Multiprofile Hospital for Active Treatment - EOOD, Clinic of Gastroenterology	Sofia
Bulgaria	Medical Center Asklepion	Sofia
Bulgaria	Medical Center Asklepion - Researches in humane medicine (EOOD)	Sofia
Bulgaria	Medical Center Hera	Sofia
Bulgaria	Medical Center Hera EOOD	Sofia
Bulgaria	UMHAT Tsaritsa Yoanna - ISUL - EAD	Sofia
Bulgaria	Medical Center VIP Clinic	Varna
Bulgaria	Medical center VIP Clinic - OOD	Varna
Croatia	University Hospital Center Split	Split
Georgia	EVEX Hospitals JSC	Kutaisi
Georgia	West Regional Center of Modern Medical Technologies Ltd	Kutaisi
Georgia	Institute of Clinical Cardiology	Tbilisi
Georgia	Israel-Georgia Medical Research Clinic Helsicore Ltd	Tbilisi
Georgia	JSC Clinic Jerarsi	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla Ltd	Tbilisi
Hungary	Clinexpert SMO	Budapest
Hungary	II. Sz. Belgyogyaszati Klinika, Semmelweis Egyetem	Budapest
Hungary	II. Sz Belgyogyasztai Intezet, Gasztroenterologia Debreceni Egyetem	Debrecen
Latvia	Polana-D	Daugavpils
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	Digestive Diseases Centre GASTRO	Riga
Latvia	Pauls Stradins Clinical University Hospital	Riga
Poland	Centrum Opieki Zdrowotnej Orkan-med	Ksawerów
Poland	Centrum Medyczne Med-Gastr	Lódz
Poland	Oddzial Kliniczny Gastroenterologii Ogólnej i Onkologicznej	Lódz
Poland	Medicome Sp. z o.o.	Oswiecim
Poland	Centrum Medyczne Medyk	Rzeszów
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warszawa
Poland	Melita Medical	Wroclaw
Russian Federation	Ekaterinburg City Clinical Hospital No. 14	Ekaterinburg
Russian Federation	Prof. S.V. Ochapovskiy Regional Clinical Hospital No.1	Krasnodar
Russian Federation	Ryzhikh State Coloproctology Research Center	Moscow
Russian Federation	LLC Novosibirskiy Gastrocenter	Novosibirsk
Russian Federation	Medical Center Healthy Family LLC	Novosibirsk
Russian Federation	State Budgetary Healthcare Institution of the Stavropol Region - Pyatigorsk Oncology Dispensary	Pyatigorsk
Russian Federation	Saratov State Medical University	Saratov
South Africa	301 Fairfield Medical Suite	Cape Town
Ukraine	Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital - Dnipropetrovsk Regional Council	Dnipro
Ukraine	Prof. O.O. Salimov City Clinical Hospital #2 - Kharkiv City Council	Kharkiv
Ukraine	Kryvyi Rih City Clinical Hospital #2	Kryvyi Rih
Ukraine	Kyiv Regional Clinical Hospital - Kyiv Regional Council	Kyiv
Ukraine	Medical Center OK!Clinic+ of International Institute of Clinical Studies LLC	Kyiv
Ukraine	Ternopil University Hospital - Ternopil Regional Council	Ternopil
Ukraine	Andrii Novak Transcarpathian Regional Clinical Hospital	Uzhhorod
Ukraine	Municipal Institution City Clinical Hospital #6 - Therapeutic Department	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
OSE Immunotherapeutics

Countries where clinical trial is conducted

Belarus,  Belgium,  Bulgaria,  Croatia,  Georgia,  Hungary,  Latvia,  Poland,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in modified Mayo Score	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	Baseline and Week 10
Secondary	Clinical Remission	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	Week 10
Secondary	Clinical efficacy of OSE-127 vs placebo	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	Week 10
Secondary	Efficacy of OSE-127 vs placebo on endoscopic remission	Number and proportion of patients with an endoscopic remission defined by an endoscopic Mayo sub-score =0	Week 10
Secondary	Efficacy of OSE-127 vs placebo on endoscopic improvement	Number and proportion of patients with endoscopic response or improvement defined by an endoscopic subscore of Mayo = 1 point	Week 10
Secondary	Efficacy of OSE-127 vs placebo on endoscopic improvement	Mean change from baseline in the endoscopic activity measured by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)	Week 10
Secondary	Overall safety and tolerability of OSE-127 in patients with moderate to severe UC	Frequency and severity of reported treatment-emergent adverse events, serious adverse events	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