Pouchitis
Conditions
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.
Interventions
DRUGAlicaforsen
DRUGPlacebo
Sponsors
Atlantic Pharmaceuticals Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium, Canada, France, Ireland, Israel, Italy, Netherlands, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alicaforsen Alicaforsen enema, 240mg once daily for 6 weeks
Alicaforsen | 69 |
| Placebo Placebo enema, once daily for 6 weeks
Placebo | 69 |
| Total | 138 |
Baseline characteristics
| Characteristic | Total | Alicaforsen | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 4 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 131 Participants | 65 Participants | 66 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) White | 116 Participants | 62 Participants | 54 Participants |
| Sex: Female, Male Female | 58 Participants | 30 Participants | 28 Participants |
| Sex: Female, Male Male | 80 Participants | 39 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 69 |
| other Total, other adverse events | 19 / 69 | 20 / 69 |
| serious Total, serious adverse events | 4 / 69 | 2 / 69 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alicaforsen | Proportion of Patients With a Reduction in Relative Stool Frequency | 22 Participants |
| Placebo | Proportion of Patients With a Reduction in Relative Stool Frequency | 16 Participants |
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alicaforsen | Proportion of Patients With Endoscopic Remission | 3 Participants |
| Placebo | Proportion of Patients With Endoscopic Remission | 3 Participants |