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

NCT02525523 | Completed Phase 3 Results

• 1 other identifier: ACH UCP-301
• Study Type: interventional
• Target: 138
• Locations: 10 countries
• Sites: 41

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.

Conditions

Pouchitis

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Alicaforsen

EXPERIMENTAL

Alicaforsen enema, 240mg once daily for 6 weeks

Drug: Alicaforsen

Placebo

PLACEBO COMPARATOR

Placebo enema, once daily for 6 weeks

Drug: Placebo

Interventions

Alicaforsen DRUG

Alicaforsen

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Atlantic Pharmaceuticals Ltd: lead

Study Sites (41)

Site Reference ID/Investigator# 1008

La Jolla, California, 92037, United States

Location

Site Reference ID/Investigator # 1005

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator#1011

Stanford, California, 94305, United States

Location

Site Reference ID/Investigator#1012

Atlanta, Georgia, 30322, United States

Location

Site Reference ID/Investigator# 1010

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 1001

Rochester, Minnesota, 55905, United States

Location

Site Reference ID/Investigator# 1003

Great Neck, New York, 11021, United States

Location

Site Reference ID/Investigator# 1006

New York, New York, 10016, United States

Location

Site Reference ID/Investigator# 1009

New York, New York, 10029, United States

Location

Site Reference ID/Investigator# 1004

Cleveland, Ohio, 44195, United States

Location

Site Reference ID/Investigator# 1002

Oklahoma City, Oklahoma, 73102, United States

Location

Site Reference ID/Investigator# 1007

Seattle, Washington, 98195-6424, United States

Location

Site Reference ID/Investigator# 0103

Brussels, 1070, Belgium

Location

Site Reference ID/Investigator# 0102

Ghent, 9000, Belgium

Location

Site Reference ID/Investigator# 0101

Leuven, 3000, Belgium

Location

Site Reference ID/Investigator# 0205

Calgary, Alberta, T2N 4Z6, Canada

Location

Site Reference ID/Investigator# 0201

Edmonton, Alberta, T6G 2X8, Canada

Location

Site Reference ID/Investigator# 0204

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Site Reference ID/Investigator# 0202

London, Ontario, N6A 5A5, Canada

Location

Site Reference ID/Investigator# 0203

Toronto, Ontario, M5G 1X5, Canada

Location

Site Reference ID/Investigator# 0403

Lille, 59000, France

Location

Site Reference ID/Investigator# 0402

Nice, 06202, France

Location

Site Reference ID/Investigator# 0401

Saint-Etienne, 42055, France

Location

Site Reference ID/Investigator# 0404

Toulouse, 31059, France

Location

Site Reference ID/Investigator# 0601

Dublin, Ireland

Location

Site Reference ID/Investigator# 0602

Dublin, Ireland

Location

Site Reference ID/Investigator# 0701

Tel Aviv, 64230, Israel

Location

Site Reference ID/Investigator# 0801

Bologna, 40138, Italy

Location

Site Reference ID/Investigator# 0804

Rome, 00152, Italy

Location

Site Reference ID/Investigator# 0803

Rome, 00168, Italy

Location

Site Reference ID/Investigator# 0802

Rozzano, 20089, Italy

Location

Site Reference ID/Investigator# 0901

Amsterdam, 1105 AZ, Netherlands

Location

Site Reference ID/Investigator# 0902

Nijmegen, 6525 GA, Netherlands

Location

Site Reference ID/Investigator# 0302

Bern, CH-3012, Switzerland

Location

Site Reference ID/Investigator# 0301

Zurich, CH-8091, Switzerland

Location

Site Reference ID/Investigator# 0504

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Site Reference ID/Investigator# 0501

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Site Reference ID/Investigator# 0503

Coventry, Warwickshire, CV2 2DX, United Kingdom

Location

Site Reference ID/Investigator# 0506

Birmingham, B15 2TH, United Kingdom

Location

Site Reference ID/Investigator# 0502

London, E1 1BB, United Kingdom

Location

Site Reference ID/Investigator# 0505

London, NW1 2BU, United Kingdom

Location

MeSH Terms

Conditions

Pouchitis

Interventions

alicaforsen

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr Chris Dunk, Director of Clinical Development
• Organization: Atlantic Pharmaceuticals

chris.dunk@atlantichc.com

+44 1799 513391

Study Officials

• Chris Dunk

  Atlantic Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2015
• First Posted: August 17, 2015
• Study Start: December 3, 2015
• Primary Completion: July 9, 2018
• Study Completion: October 29, 2018
• Last Updated: February 25, 2020
• Results First Posted: February 25, 2020

Record last verified: 2020-02

Locations

BE (3); GB (6); US (12); IL (1); IE (2); IT (4); CA (5); FR (4); NL (2); CH (2)