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: 19.0 Level: PT Classification code 10036463 Term: Pouchitis System Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2013-002952-34-BE
- Lead Sponsor
- Atlantic Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- 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 4 weeks before the
Randomisation Visit which is effectively 2 weeks before the Sreening
Visit. As a minimum the antibiotic regime will comprise ciprofloxacin
1g/day, or metronidazole 15 – 20 mg/kg/day. Subjects must have been
in active disease for a minimum of 4 weeks at the point of
randomization.
OPEN LABEL ACCESS INCLUSION CRITERIA
1.Written informed consent;
2.Previous participation to Week 26 of double blind phase
3.Demonstrated compliance with previous alicaforsen/blinded treatment
4.Current evidence of active disease, based on clinical symptoms
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 oligonucleotides including
alicaforsen hydroxymethylcellulose, methyl or propylparabens.
4. Changes in dose to strong analgesia, such as opioid containing
compounds within 4 weeks of the Screening Visit.
5. History of regular NSAID use.
6. Oral 5-aminosalicylate (5-ASA) compounds; exclude subjects 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 subjects 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 subjects 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 subjects 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. Faecal transplantation within 12 weeks of screening
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: defined as either: a) complex perianal
or pouch fistula and/or b) extensive pre-pouch ileitis with deep
ulceration
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
haematologic, renal, hepatic, metabolic, psychiatric, CNS, pulmonary or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method