Ulcerative Colitis
Conditions
Brief summary
This is a multicenter, randomized, placebo-controlled 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.
Detailed description
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 study which consists of 2 treatment phases. This study consists of a 44-week maintenance treatment phase (Part 1 and Part 2), followed by a 4-year Long Term Extension (LTE) treatment phase and a 28-days follow-up period consisting in the End of Study (EOS) visit. The maintenance phase is a 44-week double blind, placebo-controlled, phase. Subjects who are clinical responders after 8 weeks induction will be randomized to Part 1, and those who are non-clinical responders will be randomized to Part 2. At the end of the 44-week maintenance phase, subjects will continue their allocated treatment until the maintenance phase is unblinded. Once the study is unblinded, all subjects receiving obefazimod will continue their allocated treatment. Subjects receiving placebo will be allocated to obefazimod 25 mg or can terminate the study.
Interventions
DRUGABX464
Administered once daily, preferably in the morning, with food
DRUGPlacebo
Administered once daily, preferably in the morning, with food
Sponsors
Abivax S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
All eligible subjects will be randomized to either the double blind, placebo-controlled Part #1 (ABX464 50mg or 25mg or placebo) or randomized to double-blind Part #2 (ABX464 50mg or 25mg) depending on their clinical response at the end of induction.
Intervention model description
Among both induction studies, subjects assessed as responders will be randomized as follows into Part 1 of the maintenance study according to their induction treatment: * ABX464 Dose 50 mg QD * ABX464 Dose 25 mg QD * Placebo. All subjects with clinical response who were dosed with placebo in the induction studies will be randomized into the placebo group. Among both induction studies, subjects assessed as non-responders will be randomized as follows into Part 2 of the maintenance study according to their induction treatment: * ABX464 Dose 50 mg QD (all subjects who received 50 mg in induction) * ABX464 Dose 25 mg QD (all subjects who received 25 mg in induction) * Subjects who were allocated to placebo in the induction study will be randomized to obefazimod 50 mg or 25 mg in a blinded manner.
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
in maintenance phase: * 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 comply with contraception requirements as described in Section 4.4. (Contraception) of the 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 Inclusion criteria in LTE phase: * Subject must have completed the maintenance phase * Investigator and subject must assess and agree that the subject has received, and will continue to receive benefit from being in the study
Exclusion criteria
in maintenance phase: * 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 (eg. primary sclerosis cholangitis, Crohn's disease, colectomy, diverting ileostomy, colon cancer or colonic adenomas \[low or high grade dysplasia\]). * Subjects with evidence of an unstable clinical condition (eg. toxic megacolon, fulminant colitis, bowel perforation, uncontrolled ischemic disease, congestive heart failure with NYHA class 3 or 4 symptoms) during the induction study that, in the investigator's judgment, will substantially increase the risk to the subject 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, or pregnant female subjects * Introduction during induction study of prohibited medications, dosages, surgical or non-medicinal procedures indicated for UC (except antidiarrheals and motility agents for acute diarrhea). * Any changes in the laboratory values during the induction period that could jeopardize subject's safety in the opinion of the investigator. If any doubts, the investigator should contact the sponsor study medical monitor. * Subject who is planning to receive live vaccine during the study. * Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of subjects in clinical remission at Week 44 | Week 44 | The Part 1 primary objective is to compare the efficacy of ABX464 versus placebo on the proportion of subjects in clinical remission \[SFS = 0 or 1, RBS = 0 and endoscopy sub-score = 0 or 1\] at Week 44. |
| Number and percentage of all treatment-emergent adverse events (TEAEs) | Week 44 | The Part 2 primary objective is safety |
| Number and percentage of all serious adverse events (SAEs) | Week 44 | The Part 2 primary objective is safety |
| Number and percentage of all causally related TEAEs/SAEs | Week 44 | The Part 2 primary objective is safety |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with endoscopic improvement at Week 44 | Week 44 | To compare the efficacy of ABX464 versus placebo on endoscopic improvement (Mayo Endoscopic Subscore (MES) = 0 or 1) at Week 44 |
| Proportion of subjects with corticosteroid-free clinical remission | Week 44 | To compare the efficacy of ABX464 versus placebo on 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) |
| Proportion of subjects with sustained clinical remission at Week 44 | Week 44 | To compare the efficacy of ABX464 versus placebo to sustain clinical remission at Week 44 |
| Proportion of subjects with HEMI per Geboes scoring at Week 44 | Week 44 | To evaluate the efficacy of ABX464 on histologic-endoscopic mucosal improvement (HEMI) versus placebo at Week 44 |
| Proportion of subjects with endoscopic remission at Week 44 | Week 44 | To compare the efficacy of ABX464 versus placebo on endoscopic remission (MES = 0) at Week 44 |
| LTE Phase - Proportion of subjects in clinical remission at Year 1 | LTE Year 1 | To evaluate the efficacy of obefazimod on clinical remission \[SFS = 0 or 1, RBS = 0 and endoscopy sub-score = 0 or 1\] at Year 1 |
| LTE Phase - Proportion of subjects in clinical remission at Year 4 | LTE Year 4 | To evaluate the efficacy of obefazimod on clinical remission \[SFS = 0 or 1, RBS = 0 and endoscopy sub-score = 0 or 1\] at Year 4 |
| LTE Phase - Proportion of subjects with corticosteroid-free clinical remission in the subpopulation with corticosteroids at maintenance study entry | LTE Year 1 | To evaluate the efficacy of obefazimod on CS-free clinical remission (clinical remission at Year 1 and corticosteroid free for at least 12 weeks prior to Year 1 in the subpopulation with corticosteroids at maintenance study entry) |
| LTE Phase - Proportion of subjects with corticosteroid-free clinical remission in the subpopulation with corticosteroids at maintenance study entry) | LTE Year 4 | To evaluate the efficacy of obefazimod on CS-free clinical remission (clinical remission at Year 4 and corticosteroid free for at least 12 weeks prior to Year 4 in the subpopulation with corticosteroids at maintenance study entry) |
| LTE Phase - Proportion of subjects with endoscopic improvement at LTE Year 1 | LTE Year 1 | To evaluate the efficacy of obefazimod on endoscopic improvement (Mayo Endoscopic Subscore (MES) = 0 or 1) |
| LTE Phase - Proportion of subjects with endoscopic improvement at LTE Year 4 | LTE Year 4 | To evaluate the efficacy of obefazimod on endoscopic improvement (Mayo Endoscopic Subscore (MES) = 0 or 1) |
| LTE Phase - Proportion of subjects with endoscopic remission at LTE year 1 | LTE year 1 | To evaluate the efficacy of obefazimod on endoscopic remission ((Mayo Endoscopic Subscore (MES) = 0) |
| LTE Phase - Proportion of subjects with endoscopic remission at LTE year 4 | LTE year 4 | To evaluate the efficacy of obefazimod on endoscopic remission (Mayo Endoscopic Subscore (MES) = 0) |
| LTE Phase - Proportion of subjects with CS-free symptomatic remission by visit | 4 years | To evaluate the efficacy of obefazimod on CS-free symptomatic remission (symptomatic remission (SFS = 0 or 1 and RBS = 0) and corticosteroid free for at least 12 weeks prior to Week 44 in the subpopulation with corticosteroids at maintenance study entry) by visit (every 3-month) |
| LTE Phase - Proportion of subjects with HEMI per Geboes scoring at LTE Year 1 | LTE Year 1 | To evaluate the efficacy of obefazimod on histologic endoscopic mucosal improvement (HEMI) per Geboes scoring |
| LTE Phase - Proportion of subjects with HEMI per Geboes scoring at LTE Year 4 | LTE Year 4 | To evaluate the efficacy of obefazimod on histologic endoscopic mucosal improvement (HEMI) per Geboes scoring |
| LTE Phase - Proportion of subjects with HEMR per Geboes scoring at LTE Year 1 | LTE Year 1 | To evaluate the efficacy of obefazimod on histologic endoscopic mucosal remission (HEMR) versus placebo |
| LTE Phase - Proportion of subjects with HEMR per Geboes scoring at LTE Year 4 | LTE Year 4 | To evaluate the efficacy of obefazimod on histologic endoscopic mucosal remission (HEMR) versus placebo |
| LTE Phase - Proportion of subjects with sustained clinical remission at LTE Year 1, in the sub-population of subjects with clinical remission at Week 44 | LTE Year 1 | To evaluate the efficacy of obefazimod on sustained clinical remission Sustained clinical remission for the LTE is defined as clinical remission assessed at an endoscopy visit during the LTE in the sub-population of subjects in clinical remission at Week 44. |
| LTE Phase - Proportion of subjects with sustained clinical remission at LTE year 4, in the sub-population of subjects with clinical remission at Week 44 | LTE year 4 | To evaluate the efficacy of obefazimod on sustained clinical remission Sustained clinical remission for the LTE is defined as clinical remission assessed at an endoscopy visit during the LTE in the sub-population of subjects in clinical remission at Week 44. |
| LTE Phase - Proportion of subjects with sustained endoscopic improvement at LTE Year 1, in the sub-population of subjects with endoscopic improvement at Week 44 | LTE Year 1 | To evaluate the efficacy of obefazimod on sustained endoscopic improvement |
| LTE Phase - Proportion of subjects with sustained endoscopic improvement at LTE Year 4, in the sub-population of subjects with endoscopic improvement at Week 44 | LTE year 4 | To evaluate the efficacy of obefazimod on sustained endoscopic improvement |
| LTE Phase - Proportion of subjects with symptomatic remission by visit | 4 years | To evaluate the efficacy of obefazimod on symptomatic remission (SFS = 0 or 1 and RBS = 0) by visit (every 3-month) |
| LTE Phase - Proportion of subjects with sustained symptomatic remission by visit | 4 years | To evaluate the efficacy of obefazimod on sustained symptomatic remission (SFS = 0 or 1 and RBS = 0) by visit (every 3-month), in the sub-population of subjects with symptomatic remission at Week 44 |
| LTE Phase - Proportion of subjects with CS-free clinical remission at LTE Year 1 | LTE Year 1 | To evaluate the efficacy of obefazimod on CS-free clinical remission (clinical remission at Year 1 and CS-free for at least 12 weeks immediately prior to Year 1) |
| LTE Phase - Proportion of subjects with CS-free clinical remission at LTE Year 4 | LTE Year 4 | To evaluate the efficacy of obefazimod on CS-free clinical remission (clinical remission at Year 4 and CS-free for at least 12 weeks immediately prior to Year 4) |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Serbia, Slovakia, South Korea, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORSeverine Vermeire, MD, PhD
UZ Leuven, Belgium
PRINCIPAL_INVESTIGATORBruce Sands, MD, PhD
Mount Sinai Health System Digestive Disease Institute, New York USA
Outcome results
None listed