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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Belgian IBD Research and Development

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

10 Sep 2021 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen-Cilag NV

External identifiers

EU CT number

2024-514326-23-00

EudraCT number

2021-000345-41

ClinicalTrials.gov

NCT05299931

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic

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.

Secondary objectives 4

1. 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.
2. 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.
3. 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.
4. 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.

Conditions and MedDRA coding

Crohn's disease

Regulatory references

Plan to share IPD

Yes

IPD plan description

Sharing of pseudonimized individual participant data will occur with the biostatistician of Ugent. A DTA (Data Transfer Agreement) has been signed.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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, transdermal, injectable contraception, intra-uterine device, sterilisation or barrier method). Adequate contraception in males (sterilization or barrier method) if his female partner is of reproductive age.
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.

Exclusion criteria 8

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 for isolated ileitis SES-CD <4) 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 18

1. Incidence and severity of adverse events in both treatment arms.
2. Time to CD worsening (as defined in section 3.2.1 of the protocol) in both treatment arms.
3. 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.
4. 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.
5. 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.
6. 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).
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. Proportion of patients in both treatment arms in complete endoscopic remission (total SES-CD <3) at week 56 of the study.
17. Proportion of patients in both treatment arms in complete endoscopic remission (total SES-CD <3) at week 112 of the study.
18. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Belgian IBD Research and Development

Sponsor organisation

Belgian IBD Research and Development

Address

Leuvensesteenweg 643

City

Zaventem

Postcode

1930

Country

Belgium

Scientific contact point

Organisation

Belgian IBD Research and Development

Contact name

Lieven Pouillon

Public contact point

Organisation

Belgian IBD Research and Development

Contact name

Ingrid Arijs

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications