ABTECT Program (ABX464 Treatment Evaluation for ulcerative Colitis Therapy) (ABX464-107)
Published: 04/12/2023
General Information:
Patients who completed the induction treatment of 8 weeks can roll over into a subsequent maintenance study with the objective to evaluate long-term safety and efficacy of obefazimod (ABX464). The maintenance trial consists of a 44-weeks treatment period followed by a 4-weeks follow-up period.
Eligibility:
Patients meeting all the inclusion criteria and none of the exclusion criteria are eligible.
If you have not yet participated in an Abtect induction study (ABX464-105 or ABX464-106), please click HERE for information.
The main criteria are listed below:
Inclusion criteria:
- Patients must have completed the induction treatment study (ABX464-105 or ABX464-106), and patients' clinical response status must be available.
- Patients Men or women aged at least 16 years old, with a diagnosis of UC confirmed by endoscopy and histology more than 90 days prior to screening visit.
- Patients must have a moderately to severely active disease defined by Modified Mayo Score.
- Patients must have a 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 (note: failure to only 5-ASA is not accepted).
- Male and female of childbearing potential as well as their partners must use an effective method of contraception during the study and for at least 21 days after the last study drug intake.
- Investigators will review the full medical history of their patients to check for potential contra-indication for the use of obefazimod and ensure their patients eligibility.
Main exclusion criteria:
- Patients who permanently discontinued the study treatment during the induction study (either ABX464-105 or ABX464-106).
- Patients must not have ulcerative colitis limited to an isolated proctitis.
- Patients who have failed on 5-ASA therapy only are not eligible.
- Patients must not have Crohn’s disease or presence or history of fistula, indeterminate colitis, infectious/ischemic colitis or microscopic colitis.
- Patients must not have a history or current evidence of toxic megacolon, fulminant colitis, bowel perforation.
- Patients must not have a history of colon cancer, past or current evidence of low grade or high-grade colonic dysplasia and/or adenomatous polyps that have not been completely removed.
- Patients must not have a recent or planned bowel surgery or history of proctocolectomy or partial colectomy or current stoma.
- Patients with inadequate hematological and biochemical laboratory parameters obtained during the screening period are not eligible.
- Patients with active infection or chronic or recurrent infection (grade 3 or 4) or reactivation (herpes zoster) within the last 2 months prior to screening or a history of opportunistic infection while not on immunosuppressive therapy are not eligible.
Study Details:
Study description/explanation of participation:
The ABTECT program (two 8-week induction trials, one 44-week maintenance trial) is conducted in patients with moderately to severely active UC who have inadequate response, no response, a loss of response, or an intolerance to either conventional therapies and/or advanced therapies.
Eligible patients will be randomly allocated into one of three treatment groups (placebo, obefazimod 25 mg, obefazimod 50 mg), and will take one capsule orally once a day.
The initial 8-week induction period will be followed by a 28-day follow-up period. Patients who completed the induction trials can roll over into the 44-week maintenance trial.
Description of treatment or intervention (mechanism of action):
Obefazimod (ABX464) has the ability to selectively upregulate a single microRNA, called miR-124, which downregulates pro-inflammatory cytokines and chemokines, thereby “putting a brake” on inflammation. Obefazimod modulates the endogenous immune system to dampen the inflammation and control the symptoms.
Particpation requirements:
Eligible patients need to go through the following examinations during the course of the study:
- Physical examinations will be done at each visit and vital signs will be measured.
- Endoscopies with biopsies will be performed before receiving the study medication and at the end of the treatment period.
- Blood samples will be collected to check patient eligibility during the screening period, and from day 1 onwards to check their safety and perform exploratory assessments.
- Collection of stools will be done at screening to check patient eligibility and during the course of the study to assess the evolution of a marker of UC activity (fecal calprotectin).
- An electrocardiogram will be done at screening, then the day of the first treatment intake and the day of the last treatment intake.
- An eye examination (Visual acuity and Slit Lamp) will be done at screening and at week-8 visit (or End of Treatment visit for subjects early discontinuing the study).
- In sites where possible, a cardiac function sub-study consisting in a cardiac ultrasound, will be performed at the entry in the study and at week 8, and read centrally.
- An electronic device (e-Diary) will be used to collect stool frequency, rectal bleedings, nocturnal bowel movements, bowel urgency and fatigue assessment, as well as the number of capsules taken and the intake time.
Possible risks and side effects:
To date, over 1,000 patients have been treated with obefazimod as per November 30, 2022, of which more than 200 patients have been treated for at least one year, including over 150 patients who received treatment for two years or more.
Most frequently reported adverse events were headaches, which occurred early (first 10 days of treatment) and were transient (few days), mild or moderate (grade 1 or 2) and manageable with or without over-the-counter medications.
Other adverse events (≥ 5% - related and non-related) were gastrointestinal disorders (nausea, vomiting, upper abdominal pain) and musculoskeletal (arthralgia, myalgia). No clinically significant changes in laboratory parameters were detected (e.g. liver function tests, Hb, white blood cells).
Progress to Date:
In the results currently available of the Phase 2a and Phase 2b induction and maintenance trials, obefazimod has demonstrated a rapid onset of action and maintained efficacy in moderate-to-severe UC patients. The safety database of over 1,000 patients treated to date with obefazimod indicates a favorable safety and tolerability profile.
Publication highlighting the results of obefazimod (ABX464) in the Phase 2a and Phase 2b trials:
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ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomised, placebo-controlled induction trial and 48 week, open-label extension, Severine Vermeire et al., Lancet Gastroenterol Hepatol, Volume 7, Issue 11, Sept. 2022, P. 1024-1035
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Induction and long-term follow-up with ABX464 for moderate-to-severe ulcerative colitis: Results of phase 2a trial, Severine Vermeire et al., Gastroenterology, Volume 160, Issue 7, June 2021, P. 2595-2598.E3
Publications on the mechanism of action of obefazimod (ABX464):
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ABX464 (obefazimod) up-regulates miR-124 to reduce pro-inflammatory markers in inflammatory bowel diseases, Cécile Apolit et al., Clinical and Translational Gastroenterology, published online Jan. 2023
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Specific and selective induction of miR-124 in immune cells by the quinoline ABX464: a transformative therapy for inflammatory diseases, Cécile Apolit et al., Clinical and Translational Gastroenterology, published online Jan. 2023
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Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing, Audrey Vautrin et al., Nature Scientific Reports, Volume 9, Article number: 792, January 2019
Press releases issued on clinical trial results with obefazimod (ABX464) in ulcerative colitis an on publications on its mechanism of action:
Press releases issued on publications on the mechanism of action of obefazimod (ABX464):