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

NCT05299931 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: BIRD2020001
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to assess the long-term efficacy and safety of a ustekinumab 90mg subcutaneous (SC) every 4 weeks (Q4w) regimen in patients with Crohn's disease previously enrolled in the REScUE study (NCT04245215) because of secondary loss of response to a ustekinumab 90mg SC every 8 weeks (Q8w) regimen.

Conditions

Crohn Disease

Keywords

ustekinumab

Outcome Measures

Primary Outcomes (2)

• Proportion of patients in both treatment arms in steroid-free clinical remission

  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).

  Week 56

• Proportion of patients in both treatment arms in steroid-free clinical remission

  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).

  Week 112

Secondary Outcomes (17)

• Incidence and severity of adverse events in both treatment arms.

  week 112

• Time to CD worsening in both treatment arms

  week 112

• 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.

  Week 56

• 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.

  Week 112

• Proportion of patients previously enrolled to UST 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 at week 112.

  Week 112

Other Outcomes (6)

• Pharmacokinetic evaluation

  between baseline and week 112

• Time until ustekinumab discontinuation (treatment persistence).

  between baseline and week 112

• Improvements in quality-of-life based on 36-Item Short Form Survey Instrument (SF-36)

  between baseline and week 112

Study Arms (2)

Subcutaneous (SC) ustekinumab every 8 weeks (Q8w)

OTHER

Patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm will continue ustekinumab 90 mg SC Q8w if they are "Q8w responders" at the end of REScUE Patients treated with a OLE treatment regimen of ustekinumab 90 mg SC Q8w will be able to cross-over to a OLE treatment regimen of ustekinumab 90 mg SC Q4w if they meet the criteria of CD worsening at week 12 or at any timepoint beyond week 12 after entering REScUE-OLE

Drug: Ustekinumab

Subcutaneous (SC) ustekinumab every 4 weeks (Q4w)

OTHER

Patients previously enrolled to the ustekinumab 90 mg SC Q8w-arm will switch to ustekinumab 90 mg SC Q4w ("Cross-over") if they are "Q8w non-responders" at the end of REScUE OR Patients previously enrolled to the ustekinumab 90 mg SC Q4w-arm will continue ustekinumab 90 mg SC Q4w if they are "Q4w responders" at the end of REScUE

Drug: Ustekinumab

Interventions

Ustekinumab DRUG

dose escalation from every 8 weeks to every 4 weeks only in arm 2

Also known as: dose escalation only in arm 2

Subcutaneous (SC) ustekinumab every 4 weeks (Q4w); Subcutaneous (SC) ustekinumab every 8 weeks (Q8w)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Have the capacity to understand and sign an informed consent form.
• Be able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• 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.
• 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)
• Patients who developed an anaphylactic or severe allergic reaction to study medication during REScUE.
• Patients with any of the following laboratory tests at W0 of the REScUE-OLE study :
• 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
• Patients with an ongoing treatment with another concomitant biological (vedolizumab, anti-TNF), a JAK-inhibitor or any investigational product for the treatment of Crohn's disease at the end of REScUE at week 48.
• 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.
• Patients with an impassable stenosis even after attempt of endoscopic balloon dilatation.
• Patients with an intra-abdominal abscess, or patients with an intra-anal abscess without adequate drainage by e.g. a seton placement.

Sponsors & Collaborators

• Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW: lead
• Janssen Cilag N.V./S.A.: collaborator

Study Sites (1)

Ingrid Arijs

Zaventem, 1930, Belgium

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lieven Pouillon, MD

  BIRD VZW

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 29, 2022
• Study Start: September 10, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)