|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
| Moderate to severe Ulcerative Colitis
|Medical condition in easily understood language
|Ulcerative Colitis which is a type of inflammatory bowel disease
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess the efficacy of OSE-127 versus placebo on the reduction of the modified Mayo Score in moderate-to-severe UC patients who have previously failed or lost response or are intolerant to previous treatment(s)
|Secondary objectives of the trial
|_ To assess the efficacy of OSE-127 versus placebo on the rate of clinical remission
_ To assess the clinical efficacy of OSE-127 versus placebo on the rate of clinical response
_ To assess the efficacy of OSE-127 versus placebo on endoscopic remission and on endoscopic improvement
_ To assess the overall safety and tolerability of OSE-127 in patients with moderate to severe UC
|Trial contains a sub-study
|Principal 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 (i.e., histopathology report available in the patient’s file); however, a biopsy for a local histopathology assessment at screening can substitute this requirement.
6. Previous or current biologic therapy for UC with documented history of a primary non clinical response or, a secondary loss of response to at least 1 of the following agents used at a dose and regimens approved for the treatment of UC for sufficient time (including approved biosimilars):
• Anti-TNF-α agents
Or to 1 of the following investigational biologic agents (i.e. not yet approved in UC) used at a therapeutical dose (in such situations, prescreening discussions with the Medical Monitor of the study will allow to define if the conditions of non-response are met):
• Other biologic …
7. Patient currently receiving 1 or more of the following medication(s) for UC is eligible, provided that he/she has been receiving such treatment(s) for at least 4 weeks and with no change in dose or frequency in the 2 weeks prior to screening:
a. Oral aminosalicylates anticipating that the dose at screening has to be maintained until Week 10.
b. Prednisone (stable doses ≤ 20 mg/day) or equivalent, budesonide MMX (stable doses ≤ 9 mg/day), or beclomethasone dipropionate (stable doses ≤ 5 mg/day), anticipating that these stable doses have to be maintained until Week 10.
If these medications have recently been stopped, the treatment cessation must have occurred at least 2 weeks prior to screening.
8. Patients who have been previously receiving anti-TNF-α therapy or vedolizumab or ustekinumab must have discontinued this therapy ≥ 8 weeks before the date of baseline endoscopy or ≥ 5 half-lives before the
date of baseline endoscopy in case of investigational biologics agents.
9. For patients with UC >8 years, results of a surveillance colonoscopy conducted within 2 years prior to screening are required to rule out dysplasia. This full colonoscopy might be done at screening instead of the procto-sigmoidoscopy to fulfill this requirement.
10. Either chest x-ray within the 3 months prior to screening and/or a negative quantiFERON TB Gold In Tube test according to local guidelines and standard of care to exclude active or latent TB infection.
|Principal 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:
a. Elevation at screening of aspartate 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
b. Platelet count < 100,000/mm3
c. Hemoglobin (Hgb) < 8.5 g/dL
d. Neutrophils < 1500/mm3
e. Lymphocytes < 800/mm3
f. 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 highly effective birth control methods during the study (as described in Section 6.4 of the protocol) from the first study drug administration until the last follow-up visit. Women of childbearing potential will enter the study after a negative pregnancy test.
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)
15. Previous failure to more than 3 biologics including anti-TNF-α and/or anti-integrin and/or ustekinumab and/or any other biologics agents
16. Prior treatment with a JAK inhibitor
17. Clinically relevant cardiovascular, hepatic, neurologic, psychiatric, pulmonary, endocrine, or other major systemic disease that would put the patient at risk by participating in the study in the opinion of the investigator
18. A recognized hereditary, congenital, or acquired immunodeficiency disease including human immunodeficiency virus (HIV) infection and other cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia
19. Known active viral, bacterial, fungal, mycobacterial infection, or other infection or any major infection that required hospitalization or treatment with IV antibiotics or antifungal within 30 days of screening or that required treatment with oral antibiotics within 14 days of screening
20. History or known presence of chronic or recurrent infection (hepatitis B, C, HIV)
21. Any autoimmune disease, other than UC, with the exception of controlled Type I diabetes (hemoglobin A1c ≤8%) or treated hypothyroidism
22. Evidence of active malignancy
23. Live vaccine received within 4 weeks prior to screening
24. Previous treatment with lymphocyte-depleting agents such as alemtuzumab; alkylating agents such as cyclophosphamide or chlorambucil; total lymphoid irradiation; or selective B lymphocyte-depleting agents such as rituximab
25. Current or previous treatment with investigational therapy in another therapeutic clinical trial within 8 weeks or 5 half-lives before the date of baseline endoscopy
26. History of alcohol or drug abuse within 1 year of screening
27. Previous completion or withdrawal from this study. This criterion does not apply to participants undergoing rescreening procedures.
|E.5 End points
|Primary end point(s)
|Mean change from baseline in the modified Mayo Score at Week 10 exploring the clinical symptoms (stool frequency and rectal bleeding sub-scores) additionally to the endoscopic sub-score
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|_Number and proportion of patients in 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
_Number and proportion of patients with a clinical response at Week 10 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
_Number and proportion of patients with an endoscopic remission at Week 10 defined by an endoscopic Mayo sub-score =0
_Number and proportion of patients with endoscopic response or improvement at Week 10 defined by an endoscopic sub-score of Mayo ≤ 1 point
_Mean change from baseline in the endoscopic activity measured at Week 10 by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
_Adverse events (AEs), serious AEs (SAEs), AEs leading to the discontinuation of study treatment, target AEs of special interest, laboratory abnormalities, vital signs, electrocardiogram (ECG), and physical examination abnormalities
|Timepoint(s) of evaluation of this end point
|at Week 10 for the efficacy objectives and throughout the clinal trial for the safety and tolerability objectives
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months