A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of ABX464 Once Daily for Induction Treatment in Subjects With Moderately to Severely Active Ulcerative Colitis
A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of ABX464 Once Daily for Induction Treatment in Subjects With Moderately to Severely Active Ulcerative Colitis
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].
Inclusion Criteria:
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:
Subjects with the following conditions (infection):
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.
Aurora, Colorado 80014, United States
Oklahoma City, Oklahoma 73104, United States
Roanoke, Virginia 24014, United States
San Miguel de Tucumán, Tucumán Province T4000AXL, Argentina
Ciudad Autonoma Buenos Aires, C1117ABK, Argentina
Fortaleza, Ceará 60430-370, Brazil
Caxias do Sul, Rio Grande do Sul 95070-560, Brazil
Botucatu, São Paulo 18618-686, Brazil
São Bernardo do Campo, São Paulo 09715-090, Brazil
Montreal, Quebec H1T 2M4, Canada
Hyderabad, Andhra Pradesh 500048, India
Hyderabad, Andhra Pradesh 500082, India
Secunderabad, Andhra Pradesh 500003, India
New Delhi, National Capital Territory of Delhi 110025, India
Naples, 80131, Italy
Kashiwa-shi, Chiba 277-0871, Japan
Iizuka-shi, Fukuoka 820-8505, Japan
Kurume-shi, Fukuoka 830-0011, Japan
Kurume-shi, Fukuoka 830-8543, Japan
Kiryu-shi, Gunma 376-0024, Japan
Ota-shi, Gunma 373-8585, Japan
Fukuyama-shi, Hiroshima 720-8520, Japan
Hatsukaichi-shi, Hiroshima 738-8503, Japan
Kure-shi, Hiroshima 737-0023, Japan
Ibaraki, Ibaraki 311-3193, Japan
Kamakura-shi, Kanagawa 247-0056, Japan
Kawasaki-shi, Kanagawa 210-0013, Japan
Okinawa-shi, Okinawa 904-2195, Japan
Ureshino-shi, Saga-ken 843-0393, Japan
Kumagaya-shi, Saitama 360-8567, Japan
Shinjuku-ku, Tokyo-To 169-0073, Japan
Las Palmas de Gran Canaria, Las Palmas 35019, Spain