Ulcerative Colitis
Conditions
Brief summary
This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464 given at 25 or 50 mg QD in inducing clinical remission 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 \[biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators, and/or JAK inhibitors\].
Interventions
DRUGABX464
Administered once daily in the morning with food
DRUGPlacebo
Administered once daily in the morning with food
Sponsors
Abivax S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women at least 16 years old; Adolescent subjects will only be enrolled if approved by the country regulatory/health authority. If these approvals have not been granted, only subjects ≥ 18 years old will be enrolled. To be eligible, adolescent subjects must weight ≥ 40 kg and meet the definition of Tanner Stage 5 at the screening visit. * 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. * Documented diagnosis of UC confirmed by endoscopy and histology. Should endoscopy/histology results not be available at screening, results from endoscopies or biopsies taken at screening may be used. * Active disease defined by modified Mayo score (MMS) ≥ 5 with rectal bleeding subscore (RBS) ≥ 1 and endoscopy subscore (MES) of 2 or 3 (confirmed by central reader). * Subjects with documented inadequate response (defined as lack of response or loss of response or intolerance) to at least one of the following treatments: corticosteroids, immunosuppressant, biologic or biosimilar therapies, S1P receptor modulators and/or JAK inhibitors and/or new drugs approved during the study (note: failure to only 5-ASA or sulfasalazine is not accepted). * Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with the contraception requirements described in the protocol. * Subjects 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 with UC limited to an isolated proctitis (≤ 15cm from anal verge) determined by endoscopy central reading. * Subjects with primary sclerosing cholangitis or autoimmune hepatitis. * Subjects who have failed on 5-ASA or sulfasalazine therapy only. * Subjects with CD or presence or history of fistula, indeterminate colitis, infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis). * History or current evidence of toxic megacolon, fulminant colitis, bowel perforation. * History of colonic cancer or colonic low grade or high grade dysplasia adenomatous polyps, and/or at the screening endoscopy, evidence of colonic cancer or evidence of low grade or high grade dysplasia adenomatous polyps (fully removed or not). * Recent or planned bowel surgery or history of proctocolectomy or partial colectomy or current stoma. * Subjects on antidiarrheals including those working on motility (e.g., loperamide, diphenoxylate with atropine, etc.). * Subjects on probiotics (e.g., Culturelle® \[Lactobacillus GG, i-Health, Inc.\], Saccharomyces boulardii). * Subjects who do not meet the washout period requirements prior to the screening endoscopy * Subjects with the following hematological and biochemical laboratory parameters obtained during the screening period: * Hemoglobin ≤ 8.0 g dL-1 * Absolute neutrophil count \< 750 mm-3 * Platelets \< 100,000 mm-3 * Creatinine clearance \< 60 mL.min-1 (Cockroft-Gault formula) * Total serum bilirubin \> 1.5 x ULN * Alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2 x ULN * Subjects with the following conditions (infection): * Subjects with chronic or recurrent grade 3 or grade 4 infection within the last 2 months prior to screening or a history of opportunistic infection while not on immunosuppressive therapy. * Herpes zoster reactivation within the last 2 months prior to screening. * Subjects with active infection at screening or any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 1 month of screening or during screening. Fungal infection of nail beds is allowed. * Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridium difficile toxin at screening. If C. difficile is positive, subject may be treated and retested ≥ 2 weeks after completing treatment. * Subjects with HIV infection. * Subjects having acute or chronic hepatitis B infection at screening (positive for hepatitis B surface antigen \[HbsAg\], or negative for HbsAg and positive for anti-hepatitis B core antibody in conjunction with detectable HBV DNA, or detectable HBV DNA). * Subjects having acute or chronic hepatitis C infection at screening as defined by positive for hepatitis C antibody (subjects successfully treated and without recurrence ≥ 1 year with no detectable HCV RNA \[assessed centrally\] are eligible). * Active tuberculosis (TB) or untreated latent TB are ruled out. For subjects with positive or intermediate QuantiFERON test see study protocol. * Subjects with an uncontrolled ischemic heart disease and/or a history of congestive heart failure with New York Heart Association (NYHA) class 3 or 4 symptoms. * Subjects with a family or personal history of congenital or acquired long QT syndrome, or subjects with a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \[Fridericia or Bazett correction\] \>450 milliseconds for male and \> 460 milliseconds for female). * Subjects with a history of torsade de pointe (TdP). * Acute or chronic of clinically relevant pulmonary, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable central nervous system pathology such as seizure disorder, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history (note: treated autoimmune hypothyroidy and autoimmune diabetes are allowed). * Serious illness requiring hospitalization within 4 weeks prior to screening (except UC flare). * Subjects previously treated with ABX464. * Subjects with a known hypersensitivity to the active substance or to any of the excipients. * WOCBP subject who is pregnant or breast-feeding at screening, or intends to become pregnant during the study, or male subject with WOCBP partner who intends to be pregnant during the study. * Illicit drug or alcohol abuse or dependence. * Subjects who received live vaccine within 3 months prior to screening and/or who's planning to receive such a vaccine during the study duration. * Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer, and during the study. * Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. * Any condition, which in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieve Clinical Remission Per Modified Mayo Score at Week 8 | 8 weeks | To compare the efficacy of ABX464 versus placebo on clinical remission. Clinical remission is defined as stool frequency subscore (SFS) = 0 or 1 and rectal bleeding subscore (RBS) = 0, and Mayo Endoscopic Score (MES) = 0 or 1 (MES of 1 modified to exclude friability). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieve Endoscopic Improvement at Week 8 | 8 weeks | To compare the efficacy of ABX464 versus placebo on endoscopic improvement. Endoscopic improvement is defined as Mayo Endoscopic Score (MES) = 0 or 1 (MES of 1 modified to exclude friability). |
| Proportion of Subjects Who Achieve Clinical Response Per MMS at Week 8 | 8 weeks | To compare the efficacy of ABX464 versus placebo on clinical response as per Modified Mayo Score (MMS). MMS is the Modified Mayo Score. Modified Mayo score is a composite measure of ulcerative disease activity consisting of three components: stool frequency, rectal bleeding and endoscopic subscores. Each component is scored from 0 (normal or inactive disease) to 3 (severe activity). The total range score ranges from 0 to 9, with higher scores indicating more severe disease activity. Clinical Response is defined as a reduction from baseline in MMS ≥ 2 points and a relative reduction from baseline in MMS ≥ 30%, and a reduction from baseline in Rectal Bleeding Score (RBS) ≥ 1 point and/or RBS = 0 or 1. |
| Proportion of Subjects With HEMI Per Geboes at Week 8 | 8 weeks | To compare the efficacy of ABX464 versus placebo on histologic-endoscopic mucosal improvement (HEMI). HEMI is defined as endoscopic improvement associated with histologic improvement per Geboes score. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Italy, Netherlands, Poland, Portugal, South Korea, Spain, Switzerland, Turkey (Türkiye), Ukraine, 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
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 48 Participants |
| Age, Categorical Between 18 and 65 years | 146 Participants |
| Age, Continuous | 42.5 years STANDARD_DEVIATION 13.93 |
| Baseline fecal Calprotectin | 2533.58 microgram/gram (ug/g) STANDARD_DEVIATION 3761.06 |
| Baseline MMS | 6.9 units on a scale STANDARD_DEVIATION 1.06 |
| Baseline weight | 72.41 kg STANDARD_DEVIATION 18.581 |
| Duration of ulcerative colitis | 7.8 years STANDARD_DEVIATION 7.151 |
| Number of participants with a Baseline MES of 2 or 3 Baseline MES subscore = 2 | 261 Participants |
| Number of participants with a Baseline MES of 2 or 3 Baseline MES subscore = 3 | 91 Participants |
| Number of participants with at least one prior AT-IR | 149 Participants |
| Number of participants with inadequate response to JAK inhibitors among participants with AT-IR | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 34 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 114 Participants |
| Sex: Female, Male Female | 251 Participants |
| Sex: Female, Male Male | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 318 | 0 / 160 | 0 / 158 |
| other Total, other adverse events | 90 / 318 | 34 / 160 | 28 / 158 |
| serious Total, serious adverse events | 14 / 318 | 1 / 160 | 3 / 158 |
Outcome results
None listed