Efficacy of Alicaforsen in Pouchitis Patients Who Have Failed to Respond to at Least One Course of Antibiotics
- Registration Number
- NCT02525523
- Lead Sponsor
- Atlantic Pharmaceuticals Ltd
- Brief Summary
A Phase III, multi-centre, double-blind randomised controlled trial in subjects with chronic antibiotic refractory pouchitis.
Subjects will undertake a \<2 week screening period to provide baseline data and be assessed for eligibility. At the Baseline visit (Day 1) eligible subjects will be randomised on a 1:1 basis to either a) 240 mg alicaforsen enema or b) matching placebo.
Study drug will be administered once nightly (on going to bed) up to and including week 6. Following the Day 1 Visit, subjects will return to the clinic for safety and efficacy assessments at Week 3, 6, 10, 18 and 26.
Subjects may receive certain permitted medications as per Entry Criteria, which must remain at stable doses throughout the trial. Introduction of any new medication for pouchitis, or a dose change to an existing concomitant medication for pouchitis, other than those detailed in the protocol, will not be permitted.
Clinical symptoms associated with pouchitis will be recorded daily by the patient in a diary card.
Subjects will undergo endoscopic examination of their pouch (during Screening, and at Weeks 6 and 10). Where technically feasible, each endoscopy will provide at least one biopsy sample for histopathology.
In addition to endoscopic, histopathologic and symptomatic assessments, Quality of Life will be assessed.
Bloods for routine assessment, including haematology and biochemistry will be taken. Bloods and stool samples will be collected to evaluate relevant biomarkers.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 138
- Written informed consent;
- Male or female subjects, 18 years of age who have undergone an IPAA for UC
- History of pouchitis
- Overall PDAI score > 7
- Must have Chronic Antibiotic Refractory Pouchitis
- Lack of effective contraception
- Women who are pregnant or breastfeeding;
- Strong analgesia NSAID use
- Change in dose of the following permitted meds during screening and study: oral 5-aminosalicylate (5 ASA), Oral steroids,, Immunosuppressant therapy.
- Rectal products
- Biological agents: Anti-tumour necrosis factor (anti - TNF) therapy and / or vedolizumab; are not permitted within 8 weeks of the Screening Visit.
- All other agents targeted to pouchitis, including experimental agents, must have been discontinued at least 8 weeks prior to the Screening Visit, or for a period equivalent to 5 half-lives (t½) of the agent (whichever is longer)
- Anal sphincter dysfunction
- Infections to cytomegalovirus or Clostridium Difficile
- Other GI pathology (inc. intestinal malabsorption, pancreatic maldigestion etc) and differential diagnoses
- Clinically significant and/or persistent illness; which in the investigators opinion, would exclude entry into the trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo enema, once daily for 6 weeks Alicaforsen Alicaforsen Alicaforsen enema, 240mg once daily for 6 weeks
- Primary Outcome Measures
Name Time Method Proportion of Patients With Endoscopic Remission Week 10 The group of patients with an improvement in their endoscopic score between screening and week 10 as shown by an reduced modified MAYO score. Remission is defined as absence of friability and ulceration, represented by a score of ≤1.
Proportion of Patients With a Reduction in Relative Stool Frequency Week 10 Group of patients with a lowering of stool frequency from baseline to week 10, where the subject's stool frequency is represented by a MAYO subscore of ≤1 at week 10.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (41)
Site Reference ID/Investigator# 0101
🇧🇪Leuven, Belgium
Site Reference ID/Investigator# 0301
🇨🇭Zürich, Switzerland
Site Reference ID/Investigator# 1008
🇺🇸La Jolla, California, United States
Site Reference ID/Investigator# 0102
🇧🇪Gent, Belgium
Site Reference ID/Investigator# 0204
🇨🇦Vancouver, British Columbia, Canada
Site Reference ID/Investigator# 0202
🇨🇦London, Ontario, Canada
Site Reference ID/Investigator # 1005
🇺🇸Los Angeles, California, United States
Site Reference ID/Investigator# 0601
🇮🇪Dublin 4, Ireland
Site Reference ID/Investigator#1011
🇺🇸Stanford, California, United States
Site Reference ID/Investigator# 1010
🇺🇸Chicago, Illinois, United States
Site Reference ID/Investigator#1012
🇺🇸Atlanta, Georgia, United States
Site Reference ID/Investigator# 1001
🇺🇸Rochester, Minnesota, United States
Site Reference ID/Investigator# 1006
🇺🇸New York, New York, United States
Site Reference ID/Investigator# 1003
🇺🇸Great Neck, New York, United States
Site Reference ID/Investigator# 1009
🇺🇸New York, New York, United States
Site Reference ID/Investigator# 1004
🇺🇸Cleveland, Ohio, United States
Site Reference ID/Investigator# 1002
🇺🇸Oklahoma City, Oklahoma, United States
Site Reference ID/Investigator# 1007
🇺🇸Seattle, Washington, United States
Site Reference ID/Investigator# 0103
🇧🇪Brussels, Belgium
Site Reference ID/Investigator# 0205
🇨🇦Calgary, Alberta, Canada
Site Reference ID/Investigator# 0802
🇮🇹Rozzano, Italy
Site Reference ID/Investigator# 0203
🇨🇦Toronto, Ontario, Canada
Site Reference ID/Investigator# 0201
🇨🇦Edmonton, Alberta, Canada
Site Reference ID/Investigator# 0403
🇫🇷Lille, France
Site Reference ID/Investigator# 0404
🇫🇷Toulouse cedex 9, France
Site Reference ID/Investigator# 0401
🇫🇷Saint-Etienne cedex 2, France
Site Reference ID/Investigator# 0402
🇫🇷Nice cedex 3, France
Site Reference ID/Investigator# 0602
🇮🇪Dublin 8, Ireland
Site Reference ID/Investigator# 0701
🇮🇱Tel-Aviv, Israel
Site Reference ID/Investigator# 0801
🇮🇹Bologna, Italy
Site Reference ID/Investigator# 0804
🇮🇹Rome, Italy
Site Reference ID/Investigator# 0901
🇳🇱Amsterdam, Netherlands
Site Reference ID/Investigator# 0803
🇮🇹Rome, Italy
Site Reference ID/Investigator# 0902
🇳🇱Nijmegen, Netherlands
Site Reference ID/Investigator# 0504
🇬🇧Harrow, Middlesex, United Kingdom
Site Reference ID/Investigator# 0503
🇬🇧Coventry, Warwickshire, United Kingdom
Site Reference ID/Investigator# 0501
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Site Reference ID/Investigator# 0506
🇬🇧Birmingham, United Kingdom
Site Reference ID/Investigator# 0505
🇬🇧London, United Kingdom
Site Reference ID/Investigator# 0502
🇬🇧London, United Kingdom
Site Reference ID/Investigator# 0302
🇨🇭Bern, Switzerland