A Study to Test How Well Obefazimod Works and How Safe It Is for Patients with Moderately to Severely Active Ulcerative Colitis
- Trial ID
- 2022-500535-36-00
- Protocol
- ABX464-105
- Sponsor
- Abivax
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the efficacy of **ABX464** versus placebo on achieving clinical remission in subjects with moderately to severely active **ulcerative colitis**. Clinical remission is a critical endpoint in the management of ulcerative colitis, as it indicates a significant reduction in disease activity and improvement in patient quality of life.
Secondary objectives include: - Comparing the efficacy of ABX464 versus placebo on endoscopic improvement, which is important for assessing mucosal healing. - Evaluating the clinical response using the Modified Mayo Score (MMS), a validated tool for measuring disease activity. - Assessing symptomatic remission, which reflects the resolution of symptoms experienced by patients. - Investigating histologic-endoscopic mucosal improvement (HEMI), which combines histological and endoscopic assessments for a comprehensive evaluation of mucosal status. - Comparing the safety profile of ABX464 versus placebo during the induction phase, which is essential for understanding the risk-benefit ratio of the treatment.
Participants
The clinical trial involves a total of **394 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, with an age range starting from 16 years, contingent upon regulatory approval for adolescent enrollment. Participants must weigh at least 40 kg and meet the definition of Tanner Stage 5 if they are adolescents. The trial population was selected based on documented inadequate response to specific treatments such as corticosteroids, immunosuppressants, biologic therapies, S1P receptor modulators, and JAK inhibitors, excluding failure to 5-ASA alone. Participants are required to have an active disease as defined by a modified Mayo score of 5 or higher, with specific subscores for rectal bleeding and endoscopy. The trial includes a vulnerable population, and all participants must be able to comply with study visits and procedures, as well as adhere to highly effective contraception methods if applicable. Additionally, subjects should be affiliated with a health insurance policy if required by their country or state.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of ABX464 in subjects with moderately to severely active **ulcerative colitis**. The trial is conducted in multiple centers and is classified as a Phase III study. The primary objective is to compare the efficacy of ABX464 versus placebo on clinical remission, with the primary endpoint being the proportion of subjects achieving clinical remission per the Modified Mayo Score at week 8. Secondary endpoints include endoscopic improvement, clinical response, symptomatic remission, and the incidence of treatment-emergent adverse events, among others.
The trial is expected to last until November 2024, with recruitment having started in January 2023. Participants will be involved in the study for a maximum treatment period of 8 weeks. The study involves several key visits, starting with an inclusion (screening) visit to assess eligibility based on criteria such as age, documented diagnosis of ulcerative colitis, and previous treatment responses. Following the screening, eligible participants will be randomized to receive either ABX464 or a placebo in the form of hard capsules, administered orally. The study includes follow-up visits to monitor efficacy and safety outcomes, with the end-of-study visit marking the conclusion of the participant's involvement.
Participants are expected to comply with study visits and procedures as per protocol. The study may lead to early termination for participants who experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial ensures that all participants are informed and consented appropriately, with specific considerations for adolescent subjects and women of childbearing potential regarding the use of effective contraception methods. The trial is not classified as low intervention, given its focus on evaluating a new therapeutic product, ABX464, which has shown safety in previous trials.
Treatment
The clinical trial involves the administration of **ABX464**, a pharmaceutical product in the form of a hard capsule. The active substance in ABX464 is **obefazimod**, a chemical compound also known by synonyms such as ABX-464 and 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine. The medication is manufactured by ABIVAX and is administered orally. Participants in the trial receive ABX464 at a dosage of either 25 mg or 50 mg per day, with a maximum daily dose of 50 mg and a total maximum dose of 2800 mg over the course of the treatment period. The treatment duration is set for a maximum of 8 weeks.
The study also includes a **placebo** group, which receives a placebo designed to match the 25 mg and 50 mg ABX464 hard capsules. The placebo is administered in the same manner as the active treatment, ensuring the study remains double-blind. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the efficacy of ABX464 in achieving clinical remission in subjects with moderately to severely active **ulcerative colitis**.
Efficacy
The efficacy of the investigational product, **obefazimod** (ABX464), will be assessed in a randomized, double-blind, placebo-controlled, multicenter phase III clinical trial. The primary endpoint for evaluating efficacy is the proportion of subjects who achieve clinical remission as measured by the Modified Mayo Score (MMS) at week 8. Secondary endpoints include the proportion of subjects achieving endoscopic improvement, clinical response per MMS, symptomatic remission, and histological remission as per Geboes scoring, all assessed at week 8.
Data collection will occur at specified timepoints, with the primary and secondary endpoints being evaluated at week 8. The Modified Mayo Score, a validated scale, will be utilized to assess clinical remission and response. Endoscopic improvement and histological remission will be confirmed by central reading. The trial will also monitor the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and clinically significant laboratory and vital sign abnormalities to ensure comprehensive safety and efficacy evaluation.
Inclusion and Exclusion Criteria
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 > 90 days prior to baseline, confirmed by endoscopy and histology. Should histology results not be available at screening, results from 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 therapies, S1P receptor modulators and/or JAK inhibitors and/or new drugs approved during the study (note: failure to only 5-ASA is not accepted).
- 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 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 ulcerative colitis limited to an isolated proctitis (≤ 15cm from anal verge).
- Subjects who do not meet the washout period requirements prior to the screening endoscopy as described in the prohibited medication section of the study protocol.
- Subjects with hematological and biochemical laboratory parameters obtained during the screening period, as described in the protocol.
- Subjects with certain conditions (infection), as described in the 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).
- History or active malignancy (subjects with a 5-year disease free survival are eligible).
- Serious illness requiring hospitalization within 4 weeks prior to screening (except UC flare).
- Subjects previously treated with ABX464.
- Subjects with primary sclerosing cholangitis or autoimmune hepatitis.
- Pregnant or breast-feeding women.
- 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.
- Any condition, which in the opinion of the investigator, could compromise the subject’s safety or adherence to the study protocol.
- Subjects who have failed on 5-aminosalicylic acid (5-ASA) therapy only.
- Subjects with Crohn’s disease (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 colon cancer, past or current evidence of low grade or high grade of colonic dysplasia and/or adenomatous polyps that have not been completely removed.
- Recent or planned bowel surgery or history of proctocolectomy or partial colectomy or current stoma.
- Subjects on antidiarrheals (e.g., loperamide, diphenoxylate with atropine, etc.).
- Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii).
- Subjects with a known hypersensitivity to the active substance or to any of the excipients.
- Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 31 Jan 2023 | 13 |
 France | Not Yet Recruiting | 31 Jan 2023 | 30 |
 Germany | Not Yet Recruiting | 31 Jan 2023 | 19 |
 Italy | Not Yet Recruiting | 31 Jan 2023 | 31 |
 Poland | Not Yet Recruiting | 31 Jan 2023 | 60 |
 Spain | Not Yet Recruiting | 31 Jan 2023 | 12 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ABX464 | Test | CAPSULE, HARD | ORAL | 50 | 8 | PRD9689876 |
The placebo for the 25 and 50 mg ABX464 hard capsules. | Placebo | N/A | — | — | — | N/A |
ABX464 | Test | CAPSULE, HARD | ORAL | 25 | 8 | PRD4445653 |