Safety and Efficacy of AST-120 in the Treatment of Pouchitis

• Status: Completed
• Trial end date: 2008-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the study is to assess the safety and efficacy of an investigational agent, AST-120, in treating patients with active pouchitis. This is an open-label trial which means that all patients will receive AST-120 in 2g sachets (packets)three times a day for 4 weeks. All antibiotics, probiotics and nutritional agents must have been discontinued for at least 2 weeks prior to study entry. An initial group of 10 patients will be enrolled. If there are no serious adverse events associated with the study drug and at least 3 of the 10 patients respond, a second group of 10 patients will be enrolled. In the second group of patients, those patients who are considered responders or who are in remission are eligible to receive open-label AST-120 for as long as response is maintained up to a maximum of 52 weeks. Patients will have clinic visits at the start of the study and at week 4. If continuing on open label AST-120 after week 4, patients will have clinic visits every 12 weeks to assess the continuing safety and efficacy of AST-120. Endoscopies will be performed at the start of the study, week 4, week 28, week 52 or early termination.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ocera Therapeutics

Criteria

Inclusion Criteria:

• Patients with a current episode of active pouchitis (defined as having a PDAI score > 7) after IPAA for UC confirmed by endoscopy and histology

• Patients with active pouchitis who have never been treated with antibiotics (antibiotic-naive) or who have been previously treated with antibiotics and responded. Antibiotic-dependent patients may be enrolled as long as antibiotic use is discontinued for at least two weeks prior to study entry. Antibiotic-dependent pouchitis is defined as a condition in which a patient with frequent episodes (> or = 4 episodes per year) of pouchitis or persistent symptoms requires long-term, continuous antibiotic or probiotic therapy to keep the disease in remission.

• Able to give informed consent

• Able and willing to comply with all study procedures

• Females must be post-menopausal, surgically incapable of bearing children, or practicing a reliable single barrier method of birth control (condom, intrauterine devices, spermicide and barrier, Depot). Partner/spouse sterility may also qualify at the investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline. Oral contraceptives are not acceptable as there is a potential interaction with AST-120.

Exclusion Criteria:

• Patients previously treated with infliximab or any investigational immunosuppressant/immunomodulator

• Patients whose condition is severe enough that, in the investigator's opinion, withholding antibiotics for 4 weeks during the AST-120 trial is not feasible

• Patients undergoing chemotherapy for the treatment of cancer

• Antibiotic use within 2 weeks prior to the entry of the study

• Crohn's disease of the pouch, including inflammatory, fibrostenotic, or fistulizing phenotypes, based on the previously established diagnostic criteria (Shen B, et al. Am J Gastroenterol 2006 in press)

• Active specific infection of the pouch: cytomegalovirus infection and C. difficile infection

• Patients with chronic antibiotic-refractory pouchitis. Antibiotic- refractory pouchitis is defined as a condition where a patient fails to respond to a 4 week course of a single antibiotic (metronidazole or ciprofloxacin), requiring prolonged therapy of > or = 4 weeks consisting of 2 antibiotics, oral or topical 5-aminosalicylate, corticosteroid therapy, or oral immunomodulator therapy.

• History of non-inflammatory disease of the pouch: decreased pouch compliance, irritable pouch syndrome, afferent or efferent limb obstruction

• Isolated cuffitis. Patients who have active pouchitis as the predominant condition, but also have cuffitis may be enrolled.

• Strictures of the pouch inlet or outlet

• Ileal pouch patients with familial adenomatous polyposis

• History of lactose intolerance

• Known celiac disease

• Primary sclerosing cholangitis (PSC) with or without liver transplant; PSC with or without Actigall or Urso therapy

• Uncontrolled systemic diseases

• Needing oral or topical steroid treatment or 5-ASA agents

• Other major physical or major psychiatric illness within the last 6 months that in the opinion of the investigator would affect the patient's ability to complete the trial

• Active use of cholestyramine

• Active use of NSAIDs or aspirin

• Women who are pregnant, breast feeding, or planning to become pregnant during the study

• Patients who are on therapy of 5-ASA at the entry of the study