Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Safety Evaluation of ABX464 in Patients With Moderate to Severe Active Crohn's Disease

Summary: This Phase IIa study is a 16-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once a day (o.d) at 50 mg in subjects with moderate to severe active Crohn's Disease who have inadequate response, loss of response, or intolerance to prior amino-salicylates, immunosuppressant treatment, biologics, and/or corticosteroid treatment, and followed by a 4 weeks period of follow-up after the last study drug intake.

Detailed description: This Phase 2a study is a 16-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once a day (o.d) at 50 mg in subjects with moderate to severe active Crohn's Disease who have inadequate response, loss of response, or intolerance to prior amino-salicylates, immunosuppressant treatment, biologics, and/or corticosteroid treatment, and followed by a 4 weeks period of follow-up after the last study drug intake.
  Eligible patients will be randomized according to a 2/1 ratio in two different groups of treatment : ABX464 50mg OR placebo.
  After the treatment phase at week 16, all randomized patients willing to continue with the study treatment will have the possibility to enter a separate open-label study. In that case, patients will stop their participation after week 16, otherwise they will go through the 4 weeks follow-up period and the end of study visit will take place on week 20.

Eligibility: Inclusion Criteria:
  -  Men or women age 18-75 years;
  -  Patients must have a documented diagnosis (endoscopic with histology) of CD for ≥ 3 months before screening;
  -  Patients must have active moderate to severe ileal, ileocolic, or colonic CD at baseline as defined by 220 ≤ CDAI > 450,
  -  Patients must have a SES-CD score > 6 (≥4 if isolated ileal disease) at screening, assessed by ileocolonoscopy and confirmed by a central reading.
  -  Patients must be willing and able to undergo endoscopy during screening after all other inclusion criteria have been met and at the end of Week 16.
  -  Patients must have had either a documented inadequate response, no response, a loss of response, or an intolerance (defined as the occurrence of at least one Adverse Reaction leading to treatment discontinuation) to either amino-salicylates, immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, biologics (i.e. tumor necrosis factor inhibitors, vedolizumab, ustekinumab), and/or corticosteroid treatment.
  -  Patients should be able and willing to comply with study visits and procedures as per protocol;
  -  Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;
  -  Patients should be affiliated to a social security regimen (for French sites only);
  -  Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination.
  Exclusion Criteria:
  -  Patients with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis or clinical/histologic findings suggestive of ulcerative colitis;
  -  Patients with colonic dysplasia or neoplasia or adenomatous colonic polyp;
  -  Patients with presence of fistulae;
  -  Patients with current symptomatic diverticulitis or diverticulosis;
  -  Patients with obstructive colonic stricture/stenosis, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for CD during the treatment period;
  -  Patients with past medical history of clinically significant short bowel syndrome;
  -  Patients requiring parenteral nutrition;
  -  Patients with past medical history of bowel surgery resulting in an existing or current stoma;
  -  Patients with active infections at screening such as infected abdominal abscess, Clostridium difficile (stool antigen and toxin required), cytomegalovirus, tuberculous colitis and recent infectious hospitalization;
  -  Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable central nervous system pathology such as seizure disorder, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
  -  Acute, chronic or history of immunodeficiency or autoimmune disease;
  -  History of malignancy excluding patients considered cure (5 years disease free survivors);
  -  Active malignancy that may require chemotherapy or radiation therapy;
  -  Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior to baseline;
  -  Pregnant or breast-feeding woman;
  -  Illicit drug or alcohol abuse or dependence;
  -  Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer;
  -  Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

Relevance to patient case: not relevant