CClinicalTrials.gg
CompletedNCT02525523Updated Feb 25, 2020Results posted

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

A Phase 3 interventional study of Alicaforsen and Placebo in Pouchitis, sponsored by Atlantic Pharmaceuticals Ltd. Completed at 41 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-02-25.

Sponsored by Atlantic Pharmaceuticals Ltd · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
138
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Pouchitis

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03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
138 participants (actual)

Study arms

  • Experimental
    Alicaforsen

    Alicaforsen enema, 240mg once daily for 6 weeks

    Drug: Alicaforsen

  • Placebo comparator
    Placebo

    Placebo enema, once daily for 6 weeks

    Drug: Placebo

Interventions

  • DrugAlicaforsen
  • DrugPlacebo
05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Week 10

  2. 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.

    Time frame: Week 10

06

Results

Posted Feb 25, 2020

Participant flow

Participant flow — Overall Study
MilestoneAlicaforsenPlacebo
Started6969
Completed4644
Not completed2325

Outcome measures

PrimaryProportion 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.

Time frame:
Week 10
Reported as:
Count of participants · Participants
Proportion of Patients With Endoscopic Remission
ParticipantsAlicaforsenPlacebo
Proportion of Patients With Endoscopic Remission33
PrimaryProportion 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.

Time frame:
Week 10
Reported as:
Count of participants · Participants
Proportion of Patients With a Reduction in Relative Stool Frequency
ParticipantsAlicaforsenPlacebo
Proportion of Patients With a Reduction in Relative Stool Frequency2216

Adverse events

Collected over 10 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Alicaforsen0/69 (0%)4/69 (5.8%)19/69 (27.5%)
Placebo0/69 (0%)2/69 (2.9%)20/69 (29%)
Most frequent serious events
Most frequent serious events
EventAlicaforsenPlacebo
DiarrhoeaGastrointestinal disorders1/690/69
Gastrointestinal obstructionGastrointestinal disorders0/691/69
Small intestinal obstructionGastrointestinal disorders0/691/69
Anal AbsessInfections and infestations1/690/69
LipomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/690/69
Facial ParalysisNervous system disorders1/690/69
Most frequent other events
Most frequent other events
EventAlicaforsenPlacebo
Abdominal painGastrointestinal disorders2/697/69
NasopharyngitisInfections and infestations6/693/69
PouchitisGastrointestinal disorders4/695/69
Anorectal discomfortGastrointestinal disorders3/694/69
DiarrhoeaGastrointestinal disorders4/691/69

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)AlicaforsenPlaceboTotal
<=18 years000
Between 18 and 65 years6566131
>=65 years437
Sex: Female, Male
Sex: Female, Male(Participants)AlicaforsenPlaceboTotal
Female302858
Male394180
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AlicaforsenPlaceboTotal
American Indian or Alaska Native000
Asian156
Native Hawaiian or Other Pacific Islander000
Black or African American101
White6254116
More than one race000
Unknown or Not Reported51015
07

Study locations

41 sites
  • Site Reference ID/Investigator# 1008
    La Jolla, California 92037, United States
  • Site Reference ID/Investigator # 1005
    Los Angeles, California 90048, United States
  • Site Reference ID/Investigator#1011
    Stanford, California 94305, United States
  • Site Reference ID/Investigator#1012
    Atlanta, Georgia 30322, United States
  • Site Reference ID/Investigator# 1010
    Chicago, Illinois 60611, United States
  • Site Reference ID/Investigator# 1001
    Rochester, Minnesota 55905, United States
  • Site Reference ID/Investigator# 1003
    Great Neck, New York 11021, United States
  • Site Reference ID/Investigator# 1006
    New York, New York 10016, United States
  • Site Reference ID/Investigator# 1009
    New York, New York 10029, United States
  • Site Reference ID/Investigator# 1004
    Cleveland, Ohio 44195, United States
  • Site Reference ID/Investigator# 1002
    Oklahoma City, Oklahoma 73102, United States
  • Site Reference ID/Investigator# 1007
    Seattle, Washington 98195-6424, United States
  • Site Reference ID/Investigator# 0103
    Brussels, 1070, Belgium
  • Site Reference ID/Investigator# 0102
    Gent, 9000, Belgium
  • Site Reference ID/Investigator# 0101
    Leuven, 3000, Belgium
  • Site Reference ID/Investigator# 0205
    Calgary, Alberta T2N 4Z6, Canada
  • Site Reference ID/Investigator# 0201
    Edmonton, Alberta T6G 2X8, Canada
  • Site Reference ID/Investigator# 0204
    Vancouver, British Columbia V6Z 2K5, Canada
  • Site Reference ID/Investigator# 0202
    London, Ontario N6A 5A5, Canada
  • Site Reference ID/Investigator# 0203
    Toronto, Ontario M5G 1X5, Canada
  • Site Reference ID/Investigator# 0403
    Lille, 59000, France
  • Site Reference ID/Investigator# 0402
    Nice cedex 3, 06202, France
  • Site Reference ID/Investigator# 0401
    Saint-Etienne cedex 2, 42055, France
  • Site Reference ID/Investigator# 0404
    Toulouse cedex 9, 31059, France
  • Site Reference ID/Investigator# 0601
    Dublin 4, Ireland
  • Site Reference ID/Investigator# 0602
    Dublin 8, Ireland
  • Site Reference ID/Investigator# 0701
    Tel-Aviv, 64230, Israel
  • Site Reference ID/Investigator# 0801
    Bologna, 40138, Italy
  • Site Reference ID/Investigator# 0804
    Rome, 00152, Italy
  • Site Reference ID/Investigator# 0803
    Rome, 00168, Italy
  • Site Reference ID/Investigator# 0802
    Rozzano, 20089, Italy
  • Site Reference ID/Investigator# 0901
    Amsterdam, 1105 AZ, Netherlands
  • Site Reference ID/Investigator# 0902
    Nijmegen, 6525 GA, Netherlands
  • Site Reference ID/Investigator# 0302
    Bern, CH-3012, Switzerland
  • Site Reference ID/Investigator# 0301
    Zürich, CH-8091, Switzerland
  • Site Reference ID/Investigator# 0504
    Harrow, Middlesex HA1 3UJ, United Kingdom
  • Site Reference ID/Investigator# 0501
    Nottingham, Nottinghamshire NG7 2UH, United Kingdom
  • Site Reference ID/Investigator# 0503
    Coventry, Warwickshire CV2 2DX, United Kingdom
  • Site Reference ID/Investigator# 0506
    Birmingham, B15 2TH, United Kingdom
  • Site Reference ID/Investigator# 0502
    London, E1 1BB, United Kingdom
  • Site Reference ID/Investigator# 0505
    London, NW1 2BU, United Kingdom
08

References and documents

Study documents

  • Study protocol · Aug 19, 2016
  • Statistical analysis plan · Aug 19, 2016

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT02525523
Lead sponsor
Atlantic Pharmaceuticals Ltd
Responsible party
Sponsor
First posted
Aug 17, 2015
Start date
Dec 3, 2015
Primary completion
Jul 9, 2018
Completion
Oct 29, 2018
Results posted
Feb 25, 2020
Last update
Feb 25, 2020

Study contacts

Chris Dunk
study director · Atlantic Pharmaceuticals
View the source record on ClinicalTrials.gov ↗

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