Clinical Trials Register

Summary
EudraCT Number:	2017-002258-36
Sponsor's Protocol Code Number:	RETIPC/01/17
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-10-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2017-002258-36

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

STOP-Postoperative Endoscopic Recurrence Study (STOP-PER)

A.4.1

Sponsor's protocol code number

RETIPC/01/17

A.5.4

Other Identifiers

Name:

Number:

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ALFASIGMA S.P.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ALFASIGMA S.P.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ALFASIGMA S.P.A.
B.5.2	Functional name of contact point	Clinical Trials - R&D
B.5.3	Address:
B.5.3.1	Street Address	Via Ragazzi del 99
B.5.3.2	Town/ city	Bologna
B.5.3.3	Post code	40133
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390516489894
B.5.5	Fax number	00390516489671
B.5.6	E-mail	cecilia.renzulli@alfasigma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rifaximin delayed release 400 mg film coated tablet
D.3.2	Product code	Rifaximin-EIR
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RIFAXIMIN
D.3.9.1	CAS number	80621-81-4
D.3.9.2	Current sponsor code	Rifaximin-EIR
D.3.9.3	Other descriptive name	RIFAXIMINA
D.3.9.4	EV Substance Code	SUB10312MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Post-operative endoscopic Crohn’s disease recurrence

E.1.1.1

Medical condition in easily understood language

Manifestation of recurrence after surgery in patients with Crohn disease

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10013099
E.1.2	Term	Disease Crohns
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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

E.4

Principal 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-α 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 intestinal obstruction or pseudo-obstruction
 Patients with diarrhea associated with fever and/or bloody stools.
 Patients with symptoms attributed to Short Bowel Syndrome (more than cm 100 in total of small bowel resected);
 Patients with positive Clostridium difficile toxin stool assay performed at Screening.
 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 the 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.

E.5 End points

E.5.1

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 (with central blinded reading of video ileocolonoscopies).

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

E.5.2

Secondary end point(s)

 Patients with endoscopic modified Rutgeerts score ≤ 2a (lesions limited to the anastomosis or maximum of 5 aphthous lesions in the neo-terminal ileum with normal mucosa between the lesions) at 26 weeks after randomization.

 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 (vital signs, routine laboratory parameters, adverse events, withdraw due to adverse events)

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

180

F.4.2.2

In the whole clinical trial

180

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will be treated as per standard clinical practice

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-10-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-05-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-08-05

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials