Efficacy of Alicaforsen in Pouchitis Patients Who Have Failed to Respond to at Least One Course of Antibiotics

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Topical Alicaforsen Enema in Subjects With Active, Chronic, Antibiotic Refractory Primary Idiopathic Pouchitis

Conditions
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Pouchitis

Intervention / Treatment
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* Drug: Alicaforsen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alicaforsen<br>Alicaforsen enema, 240mg once daily for 6 weeks | Drug: Alicaforsen<br> <br> |
| Placebo Comparator: Placebo<br>Placebo enema, once daily for 6 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Endoscopic Remission | 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. | Week 10 | 
| Proportion of Patients With a Reduction in Relative Stool Frequency | 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. | Week 10 |