ABTECT - Maintenance

Study Overview
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Brief Summary
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This is a multicenter, randomized study to evaluate the long-term efficacy and safety of ABX464 50mg and 25mg administered once daily (QD) as maintenance therapy in subjects with moderately to severely active ulcerative colitis who have inadequate response, no response, a loss of response, or an intolerance to either conventional therapies [corticosteroids, immunosuppressant (i.e. azathioprine, 6-mercaptopurine, methotrexate)] and/or advanced therapies [biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators, and/or JAK inhibitors]. This study is the maintenance phase of both previous induction studies ABX464-105 and ABX464-106. All eligible subjects who have completed either one of the induction studies above mentioned, will be given the opportunity to take part in the present ABX464-107 maintenance study and will be randomized to either a double blind, placebo-controlled part (Part #1) or allocated to ABX464 50mg or 25mg open label treatment arms (Part #2) depending on their clinical response at the end of induction. This study consists of a 44-week treatment phase and a 28-days follow-up period consisting in the End of Study (EOS) visit.

Official Title
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A Randomized, Double-blind, Multicenter Phase III Study to Evaluate the Long-term Efficacy and Safety of ABX464 25 mg or 50 mg Once Daily as a Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: ABX464
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have completed the induction treatment study (ABX464-105 or ABX464-106), and patients' clinical response status must be available. Subjects with a valid endoscopy performed at the end of the induction study and results from central reader available at Day 1. Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures. For under-aged subjects, national requirements regarding consent should also be met. Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to use highly effective contraception methods as stated in Section 4.4. (Contraception) of this protocol. Subjects must be able and willing to comply with study visits and procedures as per protocol. Subjects should be affiliated to a health insurance policy whenever required by a participating country or state Exclusion Criteria: Subjects who permanently discontinued the study treatment during the induction study (either ABX464-105 or ABX464-106). Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (except UC) during the induction study that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study. Subjects who plan to participate in other investigational studies during the maintenance study. Male or female planning a pregnancy within the coming 12 months

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Among both induction studies, subjects assessed as responders will be randomized as follows in the maintenance study according to their induction treatment: ABX464 Dose 50 mg QD ABX464 Dose 25 mg QD (2/3 subjects from the 25mg induction dose group and 1/3 subjects from the 50mg induction group) Placebo (1/3 subjects from the 25mg induction dose group and 2/3 subjects from the 50mg induction group). All subjects with clinical response who were dosed with placebo in the induction studies will be randomized into the placebo group. Non-responder subjects are expected to opt in the maintenance study part #2 after completion of the induction studies. They will be randomly allocated into the two open-label ABX464 dose levels. ABX464 Dose 50 mg QD ABX464 Dose 25 mg QD
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX464 50mg - Responder subjects at the end of induction<br>Subjects will be orally dosed during 44 weeks | Drug: ABX464<br>* Administered once daily in the morning with food<br>* Other names: Obefazimod;|
| Experimental: ABX464 25mg - Responder subjects at the end of induction<br>Subjects will be orally dosed during 44 weeks | Drug: ABX464<br>* Administered once daily in the morning with food<br>* Other names: Obefazimod;|
| Placebo Comparator: Placebo - Responder subjects at the end of induction<br>Subjects will be orally dosed during 44 weeks | Drug: Placebo<br>* Administered once daily in the morning with food<br>|
| Experimental: ABX464 50mg - Non responder subjects at the end of induction<br>Subjects will be orally dosed during 44 weeks | Drug: ABX464<br>* Administered once daily in the morning with food<br>* Other names: Obefazimod;|
| Experimental: ABX464 25mg - Non responder subjects at the end of induction<br>Subjects will be orally dosed during 44 weeks | Drug: ABX464<br>* Administered once daily in the morning with food<br>* Other names: Obefazimod;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of subjects in clinical remission [SFS = 0 or 1, RBS = 0 and endoscopy sub-score = 0 or 1 (friability is scored as 2)] at Week 44 | The study primary objective is to evaluate the efficacy of ABX464 versus placebo on the proportion of subjects in clinical remission at Week 44. | Week 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with endoscopic improvement (Mayo Endoscopic Subscore (MES) = 0 or 1) at Week 44 | To evaluate the efficacy of ABX464 versus placebo on endoscopic improvement. | Week 44 | 
| Proportion of subjects with symptomatic remission (SFS = 0 or 1 and RBS = 0) at Week 44 | To evaluate the efficacy of ABX464 versus placebo on symptomatic remission | Week 44 | 
| Proportion of subjects with corticosteroid-free clinical remission (clinical remission at Week 44 and corticosteroid free for at least 12 weeks prior to Week 44 in the subpopulation with corticosteroids at maintenance study entry) | To evaluate the efficacy of ABX464 versus placebo on corticosteroid-free clinical remission. | Week 44 | 
| Proportion of subjects with sustained clinical remission at Week 44 | To evaluate the efficacy of ABX464 versus placebo to sustain clinical remission. | Week 44 | 
| Proportion of subjects with HEMI per Geboes scoring at Week 44 | To evaluate the efficacy of ABX464 on histologic-endoscopic mucosal improvement (HEMI) versus placebo | Week 44 | 
| Proportion of subjects with endoscopic remission (MES = 0) at Week 44. | To evaluate the efficacy of ABX464 versus placebo on endoscopic remission. | Week 44 |