Moderate to severe Ulcerative Colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Product Name: OSE-127
Product Code: OSE-127
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Lusvertikimab
CAS Number: 2375835-92-7
Current Sponsor code: OSE-127
Other d
Sponsors
OSE Immunotherapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
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-a agents • Vedolizumab • Ustekinumab - Or to 1 of the following investigational biologic agents (i.e. not yet approved in UC) used at a therapeutical dose (in such situations, pre-screening discussions with the Medical Monitor of the study will allow to define if the conditions of non-response are met): • Mirikizumab • Rizankizumab • Guselkumab • 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-a 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 126 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
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 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) 15. Previous failure to more than 3 biologics including anti-TNF-a 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 infec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: _ 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 ;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: Week 10 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Belarus, Belgium, Bulgaria, Croatia, Georgia, Hungary, Latvia, Poland, Portugal, Russian Federation, Serbia, South Africa, Spain, Ukraine
Contacts
Public ContactOSE Contact
OSE Immunotherapeutics
Outcome results
None listed