Evaluation of the Safety and Efficacy of Alicaforsen Enema compared to placebo in patients with Active, Chronic, Primary Idiopathic Pouchitis which cannot be treated efficiently with antibiotics
- Conditions
- Active, Chronic, Antibiotic Refractory Primary Idiopathic PouchitisMedDRA version: 18.1Level: PTClassification code 10036463Term: PouchitisSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2013-002952-34-NL
- Lead Sponsor
- Atlantic Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 138
1. Written informed consent;
2. Male or female subjects, 18 years of age who have undergone an IPAA for UC
3. History of pouchitis
Documented evidence of active pouchitis, based on endoscopy, symptoms and histopathology, as follows:
4. Endoscopic score = 2 on the endoscopic component of a modified MAYO score (where friability is scored as = 2)
Note: the area within 1 cm of the pouch staple, or pouch suture line, is not considered evaluable
5. Symptomatic disease (stool frequency): Subjects must demonstrate increased stool frequency compared to what is considered normal” after their IPAA operation (baseline”). Stool frequency must be an absolute value of = 6 stools per day, and = 3 stools per day above the post-IPAA baseline”.
Note: The measurement of stool frequency will be a 7-day average rounded to the nearest integer. The most recent 7 days of data will be used to calculate the average.
6. Histology: evidence of disease (Score = 2 on PDAI)
7. Overall PDAI score > 7
8. Must have Chronic Antibiotic Refractory Pouchitis
Chronic Antibiotic Refractory Pouchitis is defined as remaining in active disease despite antibiotic therapy for at least 2 continuous weeks. There is no requirement for antibiotic use to be current, or within a defined time-window. Antibiotics must be stopped 2 weeks before the Screening Visit. As a minimum the antibiotic regime will comprise ciprofloxacin 1g/day, or metronidazole 15 – 20 mg/kg/day. Patients must have been in active disease for a minimum of 4 weeks at the point of randomisation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 69
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 69
1. Lack of effective contraception
2. Women who are pregnant or breastfeeding;
3. History of allergy or adverse event to hydroxymethylcellulose, methyl or propylparabens.
4. Strong analgesia, such as opioid containing compounds is not permissible; must be stopped at the Screening Visit.
5. History of regular NSAID use.
6. Oral 5-aminosalicylate (5-ASA) compounds; exclude patients who have discontinued or changed doses of oral 5-ASA within 4 weeks of the Screening Visit.
7. Oral budesonide > 6.0 mg / day is not permitted; exclude patients who have received budesonide for < 6 weeks, or who have changed doses of budesonide within 4 weeks of the Screening Visit.
8. Oral steroids other than budesonide; exclude patients who exceed a daily dose of 15 mg prednisolone or equivalent, who have received oral steroids for < 6 weeks, or who have changed dose within 4 weeks of the Screening Visit.
9. Use of rectal compounds is not permitted; these agents must be discontinued at the Screening Visit.
10. Immunosuppressant therapy (azathioprine, 6-mercaptopurine, methotrexate, cyclosporin); exclude subjects who have received treatment for < 12 weeks, or who have changed doses within 8 weeks of the Screening Visit.
11. Biological agents: Anti-tumour necrosis factor (anti – TNF) therapy and / or vedolizumab; are not permitted within 8 weeks of the Screening Visit.
12. Previous use of alicaforsen is permitted: treatment course must have completed at least 12 weeks prior to the Screening Visit. (Alicaforsen pre-treated patients may not contribute to the primary efficacy analysis.)
13. 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)
14. Anastomotic stricture
15. Unable to undertake endoscopic evaluation
16. Faecal incontinence due to anal sphincter dysfunction
17. Infections to cytomegalovirus or Clostridium Difficile
18. History of faecal transplantation
19. Intestinal malabsorption
20. Pancreatic maldigestion
21. Suspected irritable pouch syndrome
22. Cuffitis (inflammation of the anal mucosa). Subjects with active antibiotic refractory pouchitis as the predominant condition, but who also have cuffitis, may be enrolled
23. Crohn’s disease of the pouch
24. Subjects with a history of neoplastic disease except for basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin
25. Subjects who are receiving or have received nasogastric/nasoenteric Bottle feeding, an elemental diet, or total parenteral nutrition within the 2 weeks prior to Day 1
26. Subjects with a history of clinically significant and/or persistent illness; which in the investigators opinion, would exclude entry into the trial
27. Subjects with any laboratory tests considered clinically significant at screening
28. Subjects who may be unavailable for the duration of the trial, likely to be noncompliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason including, for example, inability to retain an enema formulation
29. Pelvic sepsis should be excluded as a differential diagnosis, for example by MRI within 12 months of randomization.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the effect of alicaforsen enema on endoscopic healing and symptoms associated with pouchitis in those subjects with active antibiotic refractory pouchitis;Secondary Objective: 1. To determine the ability of alicaforsen enema to improve the clinical symptoms associated with antibiotic refractory pouchitis<br>2. To determine the effect of alicaforsen enema on health related quality of life.<br>3. To evaluate duration of effect following cessation of therapy;Primary end point(s): Co-Primary Endpoints:<br>1. Proportion of patients with endoscopic remission; defined as absence of friability and ulceration, represented by a score of = 1 (endoscopy component of a modified MAYO score) at Week 10.<br>2. Proportion of patients with a reduction in relative stool frequency, compared to the screening period, of = 30%, at Week 10.<br>Note : the area within 1 cm of the pouch suture line will not be included in the endoscopic evaluation.;Timepoint(s) of evaluation of this end point: Week 10
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Percentage change in stool frequency from baseline compared to placebo; Week 6.<br>2. Percentage change in urgency score from baseline compared to placebo; Week 6.<br>3. Proportion of patients who achieve overall PDAI <5 at both Week 6 and Week 10<br>4. Mean change from baseline in CGQL at Week 6<br>5. Proportion of subjects by Week 26, who have not received rescue” treatment for pouchitis flares, since commencing study;Timepoint(s) of evaluation of this end point: Weeks 6, 10 and 26