Clinical trial NCT02525523: Efficacy of Alicaforsen in Pouchitis Patients Who Have Failed to Respond to at Least One Course of Antibiotics
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pouchitis
Lead sponsor: Atlantic Pharmaceuticals Ltd
Sponsor class: INDUSTRY
First posted: 2015-08-17
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent;
2. Male or female subjects, 18 years of age who have undergone an IPAA for UC
3. History of pouchitis
4. Overall PDAI score \> 7
5. Must have Chronic Antibiotic Refractory Pouchitis

Exclusion Criteria:

1. Lack of effective contraception
2. Women who are pregnant or breastfeeding;
3. Strong analgesia NSAID use
4. Change in dose of the following permitted meds during screening and study: oral 5-aminosalicylate (5 ASA), Oral steroids,, Immunosuppressant therapy.
5. Rectal products
6. Biological agents: Anti-tumour necrosis factor (anti - TNF) therapy and / or vedolizumab; are not permitted within 8 weeks of the Screening Visit.
7. 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)
8. Anal sphincter dysfunction
9. Infections to cytomegalovirus or Clostridium Difficile
10. Other GI pathology (inc. intestinal malabsorption, pancreatic maldigestion etc) and differential diagnoses
11. Clinically significant and/or persistent illness; which in the investigators opinion, would exclude entry into the trial

Primary outcomes:
measure: Proportion of Patients With Endoscopic Remission
timeFrame: Week 10
measure: Proportion of Patients With a Reduction in Relative Stool Frequency
timeFrame: Week 10
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Site Reference ID/Investigator# 1008
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator # 1005
state: California
city: Stanford
country: United States
facility: Site Reference ID/Investigator#1011
state: California
city: Atlanta
country: United States
facility: Site Reference ID/Investigator#1012
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 1010
state: Illinois
city: Rochester
country: United States
facility: Site Reference ID/Investigator# 1001
state: Minnesota
city: Great Neck
country: United States
facility: Site Reference ID/Investigator# 1003
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator# 1006
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator# 1009
state: New York
city: Cleveland
country: United States
facility: Site Reference ID/Investigator# 1004
state: Ohio
city: Oklahoma City
country: United States
facility: Site Reference ID/Investigator# 1002
state: Oklahoma
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 1007
state: Washington
city: Brussels
country: Belgium
facility: Site Reference ID/Investigator# 0103
city: Gent
country: Belgium
facility: Site Reference ID/Investigator# 0102
city: Leuven
country: Belgium
facility: Site Reference ID/Investigator# 0101
city: Calgary
country: Canada
facility: Site Reference ID/Investigator# 0205
state: Alberta
city: Edmonton
country: Canada
facility: Site Reference ID/Investigator# 0201
state: Alberta
city: Vancouver
country: Canada
facility: Site Reference ID/Investigator# 0204
state: British Columbia
city: London
country: Canada
facility: Site Reference ID/Investigator# 0202
state: Ontario
city: Toronto
country: Canada
facility: Site Reference ID/Investigator# 0203
state: Ontario
city: Lille
country: France
facility: Site Reference ID/Investigator# 0403
city: Nice cedex 3
country: France
facility: Site Reference ID/Investigator# 0402
city: Saint-Etienne cedex 2
country: France
facility: Site Reference ID/Investigator# 0401
city: Toulouse cedex 9
country: France
facility: Site Reference ID/Investigator# 0404
city: Dublin 4
country: Ireland
facility: Site Reference ID/Investigator# 0601
city: Dublin 8
country: Ireland
facility: Site Reference ID/Investigator# 0602
city: Tel-Aviv
country: Israel
facility: Site Reference ID/Investigator# 0701
city: Bologna
country: Italy
facility: Site Reference ID/Investigator# 0801
city: Rome
country: Italy
facility: Site Reference ID/Investigator# 0804
city: Rome
country: Italy
facility: Site Reference ID/Investigator# 0803
city: Rozzano
country: Italy
facility: Site Reference ID/Investigator# 0802
city: Amsterdam
country: Netherlands
facility: Site Reference ID/Investigator# 0901
city: Nijmegen
country: Netherlands
facility: Site Reference ID/Investigator# 0902
city: Bern
country: Switzerland
facility: Site Reference ID/Investigator# 0302
city: Zürich
country: Switzerland
facility: Site Reference ID/Investigator# 0301
city: Harrow
country: United Kingdom
facility: Site Reference ID/Investigator# 0504
state: Middlesex
city: Nottingham
country: United Kingdom
facility: Site Reference ID/Investigator# 0501
state: Nottinghamshire
city: Coventry
country: United Kingdom
facility: Site Reference ID/Investigator# 0503
state: Warwickshire
city: Birmingham
country: United Kingdom
facility: Site Reference ID/Investigator# 0506
city: London
country: United Kingdom
facility: Site Reference ID/Investigator# 0502
city: London
country: United Kingdom
facility: Site Reference ID/Investigator# 0505
Study officials:
affiliation: Atlantic Pharmaceuticals
name: Chris Dunk
role: STUDY_DIRECTOR
References: