Clinical Trials Register

Summary
EudraCT Number:	2021-000345-41
Sponsor's Protocol Code Number:	BIRD2020001
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-15
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2021-000345-41

A.3

Full title of the trial

An Open-Label Extension and long-term efficacy and safety monitoring study of patients with Crohn’s disease previously included in the loss of RESponse to Ustekinumab treated by dose Escalation study (REScUE-OLE)

Een open-label uitbreiding en lange termijn werkzaamheids en veiligheidsmonitoringstudie van patiënten met de ziekte van Crohn die eerder werden opgenomen in de studie met verlies van RESpons op Ustekinumab behandeld door dosis-Escalatie.

Une extension ouverte et une étude de surveillance de l'efficacité et de la sécurité à long terme chez des patients atteints de la maladie de Crohn précédemment inclus dans l'essai et présentant une perte de réponse à Ustekinumab, traités par escalade de dose

A.3.1

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

Extension of the RESCUE study to follow up on long term safety and efficacy of patients with Crohn's disease that received a dose escalation after the loss of response to ustekinumab

Extension de l'étude RESCUE pour suivre la sécurité et l'efficacité à long terme des patients atteints de la maladie de Crohn qui ont reçu une augmentation de dose après la perte de réponse à l'ustekinumab.

Uitbreiding van de RESCUE-studie met het oog op de follow-up van de veiligheid en doeltreffendheid op lange termijn van patiënten met de ziekte van Crohn die een dosisescalatie hebben gekregen na het verlies van respons op ustekinumab

A.3.2

Name or abbreviated title of the trial where available

RESCUE-OLE

A.4.1

Sponsor's protocol code number

BIRD2020001

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	Belgian IBD research and development (BIRD vzw)
B.1.3.4	Country	Belgium
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	Janssen Pharmaceutica NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Belgian IBD research and development (BIRD vzw)
B.5.2	Functional name of contact point	Senior Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Leuvensesteenweg
B.5.3.2	Town/ city	Nossegem
B.5.3.3	Post code	1930
B.5.3.4	Country	Belgium
B.5.4	Telephone number	0032499317005
B.5.6	E-mail	ingrid.arijs@birdgroup.be

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	Yes
D.2.1.1.1	Trade name	Stelara 90 mg solution for injection n pre-filled syringue
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

Crohn's disease

ziekte van Crohn

La maladie de Crohn

E.1.1.1

Medical condition in easily understood language

Chronic inflammatory bowel disease

Chronische inflammatoire darmziekte

La maladie inflammatoire chronique de l'intestin

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 assess the long-term clinical efficacy of a ustekinumab 90mg SC Q4w regimen in patients with CD previously enrolled in the REScUE study because of secondary loss of response to a ustekinumab 90mg SC Q8w regimen.

Beoordelen van de klinische werkzaamheid op lange termijn van een ustekinumab 90mg SC Q4w-regime bij patiënten met CD die eerder werden ingeschreven in de REScUE-studie vanwege secundair verlies van respons op een ustekinumab 90mg SC Q8w-regime.

Evaluer l'efficacité clinique à long terme d'un régime d'ustekinumab 90mg SC Q4w chez des patients atteints de la MC précédemment inscrits dans l'étude REScUE en raison d'une perte secondaire de réponse à un régime d'ustekinumab 90mg SC Q8w

E.2.2

Secondary objectives of the trial

- To assess the long-term safety of a ustekinumab 90mg SC Q4w regimen in patients with CD previously enrolled in the REScUE study because of secondary loss of response to a ustekinumab 90mg SC Q8w regimen.
- To assess the long-term biochemical effect of a ustekinumab 90mg SC Q4w regimen in patients with CD previously enrolled in the REScUE study because of secondary loss of response to a ustekinumab 90mg SC Q8w regimen.
- To assess the long-term endoscopic effect of a ustekinumab 90mg SC Q4w regimen in patients with CD previously enrolled in the REScUE study because of secondary loss of response to a ustekinumab 90mg SC Q8w regimen.
- To assess the additional benefit of dose optimization to a ustekinumab 90mg SC Q4w regimen in patients experiencing CD worsening during treatment with a ustekinumab 90mg SC Q8w regimen.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Previous inclusion in the REScUE study and having reached the end of this study at week 48.
2. Adequate contraception in females of reproductive age (oral contraception, intra-uterine device, sterilisation or barrier method).
3. Have the capacity to understand and sign an informed consent form.
4. Be able to adhere to the study visit schedule and other protocol requirements.

E.4

Principal exclusion criteria

1. Patients previously enrolled to the ustekinumab 90 mg SC Q4w-arm during REScUE who were on concomitant steroid use >20 mg prednisone equivalents (budesonide >6 mg; beclomethasone dipropionaat >5 mg) at any time point in the last 28 days before the end of REScUE at week 48.
2. Patients previously enrolled to the ustekinumab 90 mg SC Q4w-arm during REScUE that did not reach the following criteria at the end of REScUE at week 48:
- Clinical remission (defined as average AP ≤1 and average SF ≤3) OR clinical response (defined as a drop of at least 50% in average AP and/or a drop of at least 50% in average SF as compared to REScUE baseline, and both average AP and SF no worse than REScUE baseline)
AND
- Endoscopic remission (defined as a total SES-CD <5) OR endoscopic response (defined as a drop of at least 50% in total SES-CD score as compared to REScUE baseline)
3. Patients who developed an anaphylactic or severe allergic reaction to study medication during REScUE.
4. Patients with any of the following laboratory tests at W0 of REScUE-OLE :
- Hemoglobin level <8.5 g/dL
- Platelets level <100.000 /mm3
- Serum creatinine level ≥1.7 mg/dL
- AST and ALT level >3 times the upper limit of normal range
- Direct (conjugated) bilirubin level ≥3.0 mg/dL
5. Patients with an ongoing treatment with another concomitant biological (vedolizumab, anti-TNF), a JAK-inhibitor or any investigational product for the treatment of CD at the end of REScUE at week 48.
6. Patients who experience or have an ongoing infection event confirmed by positive stool or blood testing (including gastrointestinal pathogens, tuberculosis, HIV, hepatitis B, hepatitis C) should not initiate REScUE-OLE until (i) this event has completely resolved as shown by the termination of treatment with anti-infective medication, or (ii) this event is considered to be in stable remission under anti-infective medication in case of HIV, hepatitis B and hepatitis C.
7. Patients with an impassable stenosis even after attempt of endoscopic balloon dilatation.
8. Patients with an intra-abdominal abscess, or patients with an intra-anal abscess without adequate drainage by e.g. a seton placement.

E.5 End points

E.5.1

Primary end point(s)

- Proportion of patients in both treatment arms in steroid-free clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3 without any steroid use in the previous 28 days) at both week 56 and week 112 of the study (sustained steroid-free clinical remission).

E.5.1.1

Timepoint(s) of evaluation of this end point

week 56 and week 112

E.5.2

Secondary end point(s)

- Incidence and severity of adverse events in both treatment arms.
- Time to CD worsening in both treatment arms.
- Proportion of patients in both treatment arms in steroid-free clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3 without any steroid use in the previous 28 days) at week 56 of the study.
- Proportion of patients in both treatment arms in steroid-free clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3 without any steroid use in the previous 28 days) at week 112 of the study.
- Proportion of patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm during REScUE who needed dose optimization to ustekinumab 90 mg SC Q4w at the start or during REScUE-OLE (≤week 100), and that reached steroid-free clinical remission (PRO-2 remission: average AP 1 and average SF 3 without any steroid use in the previous 28 days) at week 112.
- Proportion of patients in both treatment arms in clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3) at both week 56 and week 112 of the study (sustained clinical remission).
- Proportion of patients in both treatment arms in clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3) at week 56 of the study.
- Proportion of patients in both treatment arms in clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3) at week 112 of the study.
- Proportion of patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm during REScUE who needed dose optimization to ustekinumab 90 mg SC Q4w at the start or during REScUE-OLE (week 100), and that reached clinical remission (PRO-2 remission: average AP ≤1 and average SF ≤3) at week 112.
- Proportion of patients in both treatment arms with biomarker remission (CRP <5 mg/L and FC ≤250 µg/g) at week 56 of the study.
- Proportion of patients in both treatment arms with biomarker remission (CRP <5 mg/L and FC ≤250 µg/g) at week 112 of the study.
- Proportion of patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm during REScUE who needed dose optimization to ustekinumab 90 mg SC Q4w at the start or during REScUE-OLE (≤week 100), and that reached biomarker remission (CRP <5 mg/L and FC ≤250 µg/g) at week 112.
- Proportion of patients in both treatment arms in endoscopic remission (total SES-CD <5 or for isolated ileitis < 4) at week 56 of the study.
- Proportion of patients in both treatment arms in endoscopic remission (total SES-CD <5 or for isolated ileitis < 4) at week 112 of the study.
- Proportion of patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm during REScUE who needed dose optimization to ustekinumab 90 mg SC Q4w at the start or during REScUE-OLE (≤week 100), and that reached endoscopic remission (total SES-CD <5 or for isolated ileitis < 4) at week 112.
- Proportion of patients in both treatment arms in complete endoscopic remission (total SES-CD <3) at week 56 of the study.
- Proportion of patients in both treatment arms in complete endoscopic remission (total SES-CD <3) at week 112 of the study.
- Proportion of patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm during REScUE who needed dose optimization to ustekinumab 90 mg SC Q4w at the start or during REScUE-OLE (≤week 100), and that reached complete endoscopic remission (total SES-CD <3) at week 112.

E.5.2.1

Timepoint(s) of evaluation of this end point

week 56 and week 112

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

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

a different dose of the same product

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

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

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:

108

F.1.3

Elderly (>=65 years)

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

108

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)

After participation in the full study, continuation of treatment will be determined by the situation at that time. If the 4-weekly ustekinumab administrations have already been approved, the doctor will assess whether it is advisable to continue these 4-weekly injections. If the 4-weekly treatment schedule has not yet been approved, the doctor will decide whether the patient should return to ustekinumab treatment every 8 weeks or start another treatment in consultation with the patient.

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

2021-07-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-10

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

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