Clinical Trials Register

Summary
EudraCT Number:	2016-004112-35
Sponsor's Protocol Code Number:	NA
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-06-21
Trial 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

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2016-004112-35

A.3

Full title of the trial

Low-dose azathioprine and allopurinol- versus azathioprine monotherapy in patients with Inflammatory Bowel Disease: An investigator-initiated, open, multicentre, parallel-arm, randomized controlled trial
A SOIBD (The Swedish Organisation for the study of Inflammatory Bowel Diseases) study

A.3.1

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

A comparison between standard treatment with azathioprine and a modified treatment with a lower dose of azathioprine in combination with allopurinol for patients with inflammatory bowel disease

A.4.1

Sponsor's protocol code 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	SOIBD (The Swedish Organisation for the study of Inflammatory Bowel Diseases)
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SOIBD
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Umeå University
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Västerbotten County Council
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SOIBD
B.5.2	Functional name of contact point	Pontus Karling
B.5.3	Address:
B.5.3.1	Street Address	Department of Public Health and Clinical Medicine, division of Medicine
B.5.3.2	Town/ city	Umeå
B.5.3.3	Post code	S90187
B.5.3.4	Country	Sweden
B.5.6	E-mail	pontus.karling@umu.se

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Imurel
D.2.1.1.2	Name of the Marketing Authorisation holder	Navamedic
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Azathioprine
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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.IMP: 2
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	Yes
D.2.1.1.1	Trade name	Allopurinol
D.2.1.1.2	Name of the Marketing Authorisation holder	Nordic Drugs
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Allopurinol
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with inflammatory bowel diseae (Ulcerative colitis or Crohns disease) wh do not responding to first line therapy

E.1.1.1

Medical condition in easily understood language

Patients with inflammatory bowel disease (Ulcerative colitis and Crohns disease) who do not respond to treatment with steroids or 5-aminosalycalic acid (Ulcerative colitis)

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

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 evaluate the efficacy and safety of low dose azathioprine and allopurinol versus standard azathioprine monotherapy in patients with inflammatory bowel disease.

E.2.2

Secondary objectives of the trial

To compare:

Time to remission

Steroid and biologic treatment free remission defined as Clinical remission (HBI ≤4 or SCCAI ≤2 ) at week 52 and no need for escalation of IBD therapy.

Clinical response after week 26 and week 52 (defined as Δ3 in HBI or Δ3 in SCCAI)

The proportion of patients with Fecal calprotectin <200 μg/g (<350 μg/g if Buhlman method is used) at week 26 and 52 .

Quality of life after 52 weeks using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS).

The proportion of patients who reach therapeutics levels of E-6TGN levels (230-450 pmol/L) at week 6 and week 26.

Adverse events defined as any untoward or unfavourable medical occurrence in a human subject

Effects on intestinal permeability and microbiota

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18-80 years at the time of inclusion, weight between 50 and 100 kg.

2. Willingness to comply with all trial procedures and being available for the duration of the trial.

3. Clinical and histological verified IBD eligible for treatment with thiopurines due to steroid dependence (failure to taper steroid or starting a second course of systemic steroids within one year) or due to the need for thiopurines for other reasons (disease phenotype, i.e post-surgery decision).

4. A written informed consent to participate in the study is signed before any study-related procedures are performed.

5. A normal TPMT activity measurement (>8.9 U/ml RBC) or normal TPMT genotype (*1/*1).

6. Naïve to thiopurine treatment

E.4

Principal exclusion criteria

1. Biologic treatment (anti-TNF, vedoluzimab etc) within the last three months prior the study

2. Concurrent participation in another interventional therapy study.

3. Females who are pregnant or breastfeeding

4. Females of childbearing age and potential who are not willing or capable to use acceptable methods of contraception (oral contraceptives, condoms, diaphragms, intrauterine devices) during the entire study and for up to 3 months after the end-of-study evaluation.
5. Male patients who do not use acceptable barrier methods of contraception (condoms) during the entire course of the study and up to 3 months after the end-of-study evaluation.

6. Inability to follow the treatment protocol (as judged by the investigator)

7. Current treatment with Allopurinol.

8. Patients with gout that needs medical treatment.

9. Estimated GFR < 50 ml/ml

10. Persistent alanine aminotransferase U/L (ALT) above upper limit of the normal range.

E.5 End points

E.5.1

Primary end point(s)

Steroid and biologic treatment free remission defined as Clinical remission (HBI ≤4 or SCCAI ≤2 ) at week 26 and no need for escalation of IBD therapy.

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

6 weeks, 26 weeks, 52 weeks

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

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

Yes

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

At week 52 or at withdrawal

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

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:

100

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

120

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

120

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)

If patients tolerate therapy it will continue post trial

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

2017-08-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-04

P. End of Trial
P.	End of Trial Status	Ongoing

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