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

NCT00583076 | Completed Phase 2 DMC

• 1 other identifier: 06-908
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pouchitis

Keywords

Pouchitis; Active Pouchitis; Safety and Efficacy of AST120

Outcome Measures

Primary Outcomes (2)

• Remission induction as defined by a Pouchitis Disease Activity Index (PDAI) score < 7 (Sandborn et al, Mayo Clin Proc 1994), as well as maintenance of remission over 12 months

  4 weeks induction, 12 months maintenance of remission

• Safety: Any adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product

  4 weeks induction, 12 months maintenance of remission

Secondary Outcomes (9)

• Response defined as a > or = 3 point reduction in the 18-point PDAI scoring system

  4 weeks, weeks 28 and 52

• Reduction of PDAI clinical symptom score, range from 0 to 6 (e.g., stoll frequency returns to the normal baseline)

  4 weeks, weeks 28 and 52

• Reduction of PDAI endoscopic score, range from 0 to 6

  4 weeks, weeks 28 and 52

• Reduction of PDAI histology score, range from 0 to 6

  4 weeks, weeks 28 and 52

• Need for rescue medication or increased quantity of antidiarrheal medication used during the trial

  4 weeks, weeks 28 and 52

Study Arms (1)

1

EXPERIMENTAL

AST-120, 2grams, three times daily

Drug: AST-120

Interventions

AST-120 DRUG

AST-120, 2grams,three times daily for 4 weeks. Responders in the second cohort of patients are eligible to receive AST-120 for up to 52 weeks.

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ocera Therapeutics: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (40)

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MeSH Terms

Conditions

Pouchitis

Interventions

AST 120

Condition Hierarchy (Ancestors)

Ileitis; Enteritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Ileal Diseases

Study Officials

• Bo Shen, MD

  Clevland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 31, 2007
• Study Start: February 1, 2007
• Primary Completion: March 1, 2008
• Study Completion: May 1, 2008
• Last Updated: June 18, 2014

Record last verified: 2014-06

Locations

US (1)