Loss of RESponse to Ustekinumab Treated by Dose Escalation

NCT04245215 | Completed Phase 3 Results DMC

• 1 other identifier: BIRD2018001
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to investigate the effect of re-induction with ustekinumab ≈6mg/kg IV followed by two different maintenance dosing regimens 90 mg subcutaneous every 8 weeks (Q8W) vs 90 mg subcutaneous every 4 weeks(Q4W) on clinical, biological and pharmacological outcomes in patients with Crohn's disease who show a secondary loss of response over time

Conditions

Crohn Disease

Keywords

dose escalation; ustekinumab

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Steroid Free Clinical Remission and Fecal Calprotectin<250µg/g at Week 48

  Proportion of patients with steroid free clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) and fecal calprotectin\<250µg/g at week 48. \[stool frequency (ST): average number of liquid stools for 1 week abdominal pain (AP): average scoring for abdominal pain for 1 week (0=none; 1=mild, 2=moderate; 3= severe)\]

  week 48

Secondary Outcomes (7)

• Proportion of Patients With Complete Endoscopic Remission at Week 48

  week 48

• Proportion of Patients With Endoscopic Remission at Week 48

  week 48

• Proportion of Patients With Endoscopic Response at Week 48

  week 48

• Proportion of Patients With Clinical Remission at Week 8

  week 8

• Proportion of Patients With Clinical Remission at Week 48

  week 48

Study Arms (2)

1. Subcutaneous ustekinumab every 8 weeks

PLACEBO COMPARATOR

re-induction (≈6mg/kg) intravenous ustekinumab followed by 90 mg Subcutaneous ustekinumab every 8 weeks (Q8W) for 48 weeks - receiving Q8W placebo to mimic Q4W injections

Drug: Ustekinumab

2. Subcutaneous ustekinumab every 4 weeks

ACTIVE COMPARATOR

re-induction (≈6mg/kg) intravenous ustekinumab followed by 90 mg Subcutaneous ustekinumab every 4 weeks (Q4W) for 48 weeks

Drug: Ustekinumab

Interventions

Ustekinumab DRUG

re-induction and dose escalation form every 8 weeks to every 4 weeks only in arm 2

Also known as: dose escalation only in arm 2

1. Subcutaneous ustekinumab every 8 weeks; 2. Subcutaneous ustekinumab every 4 weeks

Eligibility Criteria

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

You may qualify if:

• ≥18 years
• Diagnosis of Crohn's disease by endoscopic and/or radiologic examination.
• Patient currently treated with ustekinumab, independent of previous biological exposure.
• Patients treated with maintenance dose of ustekinumab subcutaneous 90 mg every 8 weeks
• Documented primary response at any time point during induction (up to week 20) defined as a clinical response (physician discretion) AND confirmed by either any of the following:
• \. A documented decrease in biomarkers based on a value during induction period compared to a value prior to ustekinumab induction (max. 3 months prior to start of ustekinumab induction)
• a. A decrease in CRP OR b. A decrease in FCP 2. A documented endoscopic improvement (evaluation during the induction period compared to an evaluation prior to ustekinumab induction (max. 6 months prior to start of ustekinumab induction) 6. Documented loss of response after induction (at any timepoint after week 16) assessed by the physician as moderate to severe active Crohn's disease. The increase in symptoms reported by the patient is defined as Patient Reported Outcome-2 (Abdominal Pain \> 1 AND Stool Frequency \> 3) AND confirmed by either any of the following\* :
• Documentation of endoscopic lesions in at least one segment of the ileum or colon as assessed by ileocolonoscopy AND a documented increase in biomarkers based on an increased value compared to the lowest value obtained during induction or after week 16 ustekinumab induction
• An increase in CRP and \> 5 mg/L OR
• An increase in FCP and \> 250µg/mg
• A documented relapse on endoscopy : Presence of mucosal ulcers in at least one segment of the ileum or colon and a SES-CD ≥ 6 (for patients with isolated ileitis ≥ 4), as assessed by ileocolonoscopy.
• \. Adequate contraception in female of reproductive age (oral contraception, intra uterine device, sterilisation or barrier method) 8. Have the capacity to understand and sign an informed consent form. 9. Be able to adhere to the study visit schedule and other protocol requirements.
• \. All Crohn's Disease treatments stable for at least 2 weeks prior to baseline.
• \* the criterium used to proof loss of response does not have to be identical to the one used to proof primary response : e.g. one can use an increase in biomarkers to proof primary response and a relapse on endoscopy to proof loss of response

You may not qualify if:

• Ongoing treatment with
• other concomitant biological (vedolizumab, anti-TNF)
• Steroids \>20 mg prednisolone or equivalent at baseline (budesonide \>6 mg, \> 5mg beclomethasone dipropionate at baseline)
• Q4w ustekinumab (ustekinumab treatment every four weeks)
• Women that are pregnant, nursing, or planning pregnancy
• Have screening laboratory test results within the following parameters:
• Haemoglobin \< 8.5 g/dL
• Platelets \< 100,000 /mm3
• Serum creatinine ≥ 1.7 mg/dL
• aspartate aminotransferase and alanine aminotransferase \> 3 times the upper limit of normal range
• Direct (conjugated) bilirubin ≥ 3.0 mg/dL.
• Have current signs or symptoms of infection confirmed by positive stool or blood testing (including gastrointestinal pathogens, tuberculosis, human immunodeficiency virus, hepatitis B, hepatitis C).
• Patients with a positive stool sample for gastrointestinal pathogen including Clostridium difficile.
• Evidence of current or previous clinically significant disease, medical condition other than Crohn's Disease, finding of the medical examination, or laboratory value at the screening visit outside the reference range that is of clinical relevance, that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
• Patients with an ileostomy

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

Related Publications (1)

• Peter Bossuyt, Rahier JF, Baert F, Louis E, Macken E, Lobaton T, Busschaert J, Peeters H, Dewint P, Franchimont D, Willandt B, Claessens C, Vansteenkiste L, Dewit O, Ferrante M; Belgian IBD Research and Development (BIRD) group, Severine Vermeire. The Effect of Dose Intensification After Secondary Loss of Response to Ustekinumab in Crohn's Disease: Results of the REScUE Study. Gastroenterology. 2026 Feb 24:S0016-5085(26)00146-0. doi: 10.1053/j.gastro.2026.01.042. Online ahead of print.

  PMID: 41747777 DERIVED

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

Results Point of Contact

• Title: Ingrid Arijs
• Organization: Belgian IBD Research and Development (BIRD)

ingrid.arijs@birdgroup.be

0499317005

Study Officials

• Peter Bossuyt, MD

  BIRD (Belgian IBD Research and Development) vzw

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: January 28, 2020
• Study Start: March 11, 2020
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: April 13, 2026
• Results First Posted: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)