Phase II clinical trial, conducted in different sites, with random assignation of treatment, where neither the patient or the medical doctor know the assigned treatment, drug or placebo, to evaluate the efficacy and safety of Rifaximin delayed release 400 mg tablet in the prevention of post-operative endoscopic Crohn’s disease recurrence

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2017-002258-36-BE
• Date of registration: 02/10/2017
• Prospective Registration: Yes
• Primary sponsor: ALFASIGMA S.P.A.
• Public title: Phase II clinical trial, conducted in different sites, with random assignation of treatment, where neither the patient or the medical doctor know the assigned treatment, drug or placebo, to evaluate the efficacy and safety of Rifaximin delayed release 400 mg tablet in the prevention of post-operative endoscopic Crohn’s disease recurrence
• Scientific title: A Phase II, multicentre, double-blind, randomised, placebo-controlled study of Rifaximin delayed release 400 mg tablet: clinical efficacy and safety in the prevention of post-operative endoscopic Crohn’s disease recurrence - STOP-Postoperative Endoscopic Recurrence Study (STOP-PER)
• Date of first enrolment: 05/02/2018
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002258-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Netherlands, Spain

Contacts

• Name: Cecilia Renzulli
• Affiliation: ALFASIGMA S.P.A.

• Name: Cecilia Renzulli
• Affiliation: ALFASIGMA S.P.A.

Key inclusion & exclusion criteria

Inclusion criteria:
? Patients of both sexes aged between 18 and 75 years old, inclusively.
? Patients with diagnosis of CD, who had undergone curative ileocolonic resection, with ileocolonic anastomosis and for whom a randomization within 45 days from surgical intervention is feasible.
? If the patients had an end or loop ileostomy within 1 year prior to randomization, they can be included, but stoma closure should occur within 45 days prior to randomization.
? Patients have had faecal stream restoration at least 14 days prior to randomization.
? Patients must have at least one of the following risk factors for the development of early/severe post-operative endoscopic recurrence of their CD:
1) qualifying surgery that was their second intestinal resection within 10 years
2) third or more intestinal resections,
3) surgery for a penetrating CD complication (e.g., abscess or fistula), or
4) smoking 10 or more cigarettes per day for the past year.

? Patients treated with glucocorticosteroids (systemic or topical) must discontinue treatment within 6 weeks after surgery.

? Patients are capable of and willing to adhere to the study protocol requirements.

? Patients have provided signed and dated written informed consent.

? Female patients must be:

? post-menopausal (at least 2 years without spontaneous menses), or
? surgically sterile (bilateral tubal ligation, or hysterectomy, or ablation of both ovaries),
? or have a negative urine pregnancy test result at screening and at randomization and agree to use an acceptable method of contraception throughout their participation in the study. Acceptable methods of contraception include: condom and spermicide; intrauterine device (IUD), diaphragm with spermicide; hormonal methods (oral contraceptives, patches, implants, injectable or ring) with a documented failure rate of less than 1% per year,
? or commit to absolute and continuous sexual abstinence

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 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
? Presence of macroscopic evidence for CD proximally or distally to the site of resection (presence of frank erythema, oedema, aphthae, ulcers or wall thickening > 3 mm, or creeping fat) according to the surgeon or previous imaging
? Patients who had strictureplasties at index surgery
? Patients with an ileorectal anastomosis
? Patients with active perianal Crohn’s disease
? Patients treated with (treatment which was not discontinued at the time of surgery):
? Aminosalicylates
? Any biologicals (e.g., TNF-a inhibitor, natalizumab, or
similar drugs)
? Azathioprine, 6-mercaptopurine
? Methotrexate,
? Cyclosporine, tacrolimus, sirolimus, mycophenolate
mofetil, or similar drugs
? antibiotics specific for CD such as metronidazole or
ciprofloxacin
? Patients with active infectious, ischemic, or immunological diseases with GI involvement
? Patients with symptoms attributed to Short Bowel Syndrome (more than cm 100 in total of small bowel resected);
? Patients with sepsis or other post-operative complications necessitating use of antibiotics for more than 14 days after surgery.
? Patients with colorectal stenosis precluding ileocolonoscopy.
? Patients who had qualifying ileocolonic resection for dysplasia or cancer without ongoing inflammation
? Hepatic Impairment defined as severe (Child-Pugh C) hepatic impairment or patients with MELD (Model for End-Stage Liver Disease) score > 25.
? Patients with an alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 upper limit of normal (ULN) at randomization.
? Patients with severe cardiac insufficiency (NYHA, New York Heart Association classes 3 – 4).
? Patient has a history of sensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any of the components of Rifaximin -EIR or placebo (see list in protocol at section 10.2.1).
? Patients with kidney failure at randomization.
? Any condition or circumstance that would prevent completion of the study or interfere with analysis of study results, including a history of drug or alcohol abuse, mental illness or non-compliance with treatments or visits, with immunological (including HIV infection), haematological, or neoplastic disease.
? Pregnant or nursing woman
? Patients who have donated 250 ml or more of blood in the last 3 months.
? Patients who have used any investigational drug (except biological therapies) within 3 months prior to screening.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Post-operative endoscopic Crohn’s disease recurrence
MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Rifaximin delayed release 400 mg film coated tablet
Product Code: Rifaximin-EIR
Pharmaceutical Form: Coated tablet
INN or Proposed INN: RIFAXIMIN
CAS Number: 80621-81-4
Current Sponsor code: Rifaximin-EIR
Other descriptive name: RIFAXIMINA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1600-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To demonstrate the efficacy of Rifaximin- EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg) versus placebo in the maintenance of clinical remission.
To evaluate the safety profile of Rifaximin-EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg)
Assess the effects of Rifaximin-EIR treatment on biological (inflammatory) markers of disease.
Evaluate the effects of Rifaximin -EIR treatment on quality of life

Timepoint(s) of evaluation of this end point: 26 weeks

Primary end point(s): The primary end point of this trial will be the proportion of patients with endoscopic recurrence at 26 weeks after randomization defined as Rutgeerts score =i2.

Main Objective: To demonstrate the efficacy of Rifaximin –EIR 400 mg Tablet (800mg /BID, total daily dose 1600 mg) versus placebo in the prevention of endoscopic Crohn’s disease recurrence following ileocolonic resection.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At week26
4-8-16-26-28 weeks
4-8-16-26-28 weeks
At week26
At week26
4-8-16-26-28 weeks
4-8-16-26-28 weeks
At randomization visit, week 4-8-16-26-28

Secondary end point(s): ? Patients with endoscopic Rutgeerts score
? Clinical recurrence according to CDAI score (defined as an increase higher than 70 points in CDAI score from baseline and CDAI>220 points; CDAI will be assessed at each visit).

? Proportion of patients with clinical symptom remission according to PRO defined by (1) the total number of liquid/very soft stools for the 7 days prior to each visit being = 10 (from CDAI Item 1); AND (2) an abdominal pain rating of = 1(from CDAI Item 2) on each day for the 7 days prior to each visit.

? Development of a new/re-draining fistula or abscess by week 26

? Time to clinical recurrence

? Change from baseline in CRP and faecal calprotectin at each visit during the Treatment Period.

? Change from baseline in indices of health outcomes (SF-36®) at Week 26.

? Assessments of safety will be based on the following:
- vital signs (including blood pressure, pulse, temperature and body weight);
- routine laboratory parameters (haematology, chemistry, urinalysis);
- adverse events;
- withdraw due to adverse events (AEs).

Secondary ID(s)

2017-002258-36-DE

RETIPC/01/17

Source(s) of Monetary Support

ALFASIGMA S.P.A.

Ethics review

Status: Approved
Approval date: 05/02/2018
Contact: