A study to evaluate the long-term efficacy and safety of Obefazimod (ABX464) in patients with moderate to severe active ulcerative colitis (UC) taking 25 mg or 50 mg of Obefazimod or placebo once daily.

Résumé de l'étude

The study investigates the long-term efficacy and safety of Obefazimod in patients with moderate to severe active UC who have completed the induction study (either ABX464-105 or ABX464-106; only ABX464-105 is being conducted in Switzerland). Obefazimod is a novel, orally administered anti-inflammatory drug candidate that specifically increases the production of a molecule called miR-124, which is naturally produced by the human body and has anti-inflammatory properties. Clinical experiences with individuals treated with Obefazimod at doses of 50 mg and 25 mg show that both doses are relevant as induction and maintenance treatment of UC in terms of efficacy and have a favorable short- and long-term safety profile. This study is the maintenance study of the induction studies ABX464-105 and ABX464-106 and consists of a 44-week treatment period and a 28-day follow-up period. The primary objective is to compare the efficacy of Obefazimod versus placebo in terms of clinical remission at week 44. A specific scoring system, developed to determine the severity of the disease, called the Modified Mayo Score (MMS), will be used. The key secondary efficacy objectives are the comparison: - of the efficacy of Obefazimod versus placebo regarding endoscopic improvement at week 44 - of the efficacy of Obefazimod versus placebo regarding symptomatic remission - of the efficacy of Obefazimod versus placebo regarding the healing process of the intestine - of the efficacy of Obefazimod versus placebo regarding corticosteroid-free clinical remission (if patients no longer require corticosteroids for the treatment of the disease)

(BASEC)

Intervention étudiée

The maintenance study is divided into 2 parts. Patients showing improvement in their disease at the end of the induction study participate in part 1 and receive either Obefazimod 50 mg, Obefazimod 25 mg, or placebo, depending on the treatment they received during the induction study:

- Patients treated with 50 mg during the induction study will receive either 50 mg or 25 mg of Obefazimod or placebo during the maintenance study.

- Patients treated with 25 mg during induction may receive 25 mg of Obefazimod or placebo during the maintenance study.

- Patients treated with placebo during induction who have shown improvement will continue to receive placebo during the maintenance study.

Overall, patients have a 2-to-3 chance of receiving the investigational drug Obefazimod and a 1-to-3 chance of receiving placebo. A placebo looks exactly like Obefazimod but contains no active ingredient. Double-blind means that neither the patients nor the physician will know until the end of the study which treatment is being administered.

Patients whose UC has not improved under study treatment will be assigned to a double-blind, uncontrolled part 2 and randomized into 2 treatment arms to receive either one capsule per day of Obefazimod 25 mg or Obefazimod 50 mg. Patients from part 1 whose disease worsens will also switch to part 2 as soon as the relapse is confirmed.

It is expected that approximately 1100 participants will take part in the Obefazimod-107 maintenance study at approximately 259 trial centers worldwide. The investigational drug will be provided in capsule form (in blister packs) to be taken orally once daily.

Patients in part 1 will come in 7 times and patients in part 2 will come in 8 times during the treatment period between day 1 and the end-of-treatment visit, as well as one last time for the end-of-study visit.

Eligible patients will undergo the following examinations during the study:

- At each visit, a physical examination will be performed and vital signs will be measured.

- Using an electronic device (e-diary), stool frequency, rectal bleeding, nighttime bowel movements, urgency of bowel movements, and fatigue, as well as the timing of the investigational drug intake will be recorded.

- During and at the end of the treatment period, 2 centrally evaluated endoscopies with biopsies will be performed. If there is suspicion of a relapse or worsening of the disease, an additional endoscopy may be requested.

- Blood samples will be taken: A total of up to 201 ml of blood will be collected from day 1 to check safety and conduct exploratory assessments.

- During the study, stool samples will be collected to assess the development of fecal calprotectin, a marker for UC activity.

- Throughout the study, 3 electrocardiograms will be performed.

- For patients who participated in the optional cardiac safety sub-study during the induction study, additional echocardiograms will be performed at week 28 and week 44 or upon treatment discontinuation at the end-of-treatment visit.

- If there is suspicion of worsening of the disease, patients may be invited for an unscheduled visit:

- Patients experiencing a relapse during part 1 will be assigned to the Obefazimod 50 mg arm of part 2.

- Patients experiencing a relapse during part 2 will terminate the study early if the definition of worsening of the disease is met.

- Eye examinations at week 8 (only for patients in part 2), week 28, and week 44 (or end-of-treatment visit for patients who terminate the study early).

(BASEC)

Maladie en cours d'investigation

UC belongs to the group of inflammatory bowel diseases (IBD), characterized by a misregulated immune response and associated with chronic inflammation of the rectum and colon. The cause of UC is unknown, but it is believed that genetic, environmental, and immunological factors contribute to its development. UC is typically diagnosed at the end of adolescence/early adulthood, at a time when individuals are studying, seeking employment, and starting families. Quality of life is dramatically affected, from direct physical disabilities to financial burdens. Among individuals suffering from UC, 66% report being affected at work and 73% in their leisure activities. More broadly, UC also burdens immediate family members and affects the family's quality of life. Most patients present with mild to moderate UC at diagnosis, but about one-third of patients develop moderate to severe UC. Until 2005, when the first biologic (Infliximab) was approved for UC, conventional therapies such as 5 AZA, corticosteroids, and immunosuppressants were primarily used to treat these patients. Subsequently, further advanced therapies with new biologics (new TNF inhibitors with Adalimumab and Golimumab, anti-integrin inhibitors with Vedolizumab, and IL 23 inhibitors with Ustekinumab) and more recently JAK inhibitors (e.g., Tofacitinib, Filgotinib, Upadacitinib) and S1P modulators (e.g., Ozanimod) have been introduced. At the end of the induction phase (i.e., the initiation phase), the percentage of patients responding to treatment is quite high (between 50 and 70%), but only a few are in remission (20-30% of patients with inactive disease). After 1 year of treatment, some patients progress from clinical response to clinical remission, while others lose response over time.

(BASEC)

Sponsor

ABIVAX. S.A, Paris, France IQVIA AG, Branch Basel

(BASEC)

Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)

Commission cantonale d'éthique de Berne

(BASEC)

Date d'approbation du comité d'éthique

17.07.2023

(BASEC)

Résultats de l'essai