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| Name | Class |
|---|---|
| Janssen Cilag N.V./S.A. | INDUSTRY |
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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
The study is a prospective double blind interventional study in patients with Crohn Disease treated with ustekinumab that show an objective secondary loss of response to ustekinumab after induction treatment (>Week 16). Patients can be screened during a four week period. The screening includes a clinical, biochemical and endoscopic assessment. Patients will be randomized 8 weeks after the last subcutaneous injection with ustekinumab. All patient will receive an intravenous re-induction with ustekinumab ≈6mg/kg at baseline (8 weeks after last subcutaneous administration). After the intravenous re-induction, the patients receive either ustekinumab 90 mg subcutaneous Q4W or Q8W (altered with q8w placebo to mimic Q4W injections) till week 48. Clinical and biochemical evaluation will be planned every 8 weeks until week 36 with a final evaluation at week48. Primary endpoint will be assessed at week 48. Final assessment at week 48 will include clinical, biochemical and endoscopic evaluation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ustekinumab | Drug | re-induction and dose escalation form every 8 weeks to every 4 weeks only in arm 2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Complete Endoscopic Remission at Week 48 | Proportion of patients with complete endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD )<3) at week 48 | week 48 |
| Proportion of Patients With Endoscopic Remission at Week 48 |
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Inclusion Criteria:
1. 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
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.
7. 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.
10. 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
Exclusion Criteria:
Ongoing treatment with
Women that are pregnant, nursing, or planning pregnancy
Have screening laboratory test results within the following parameters:
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
Patients that received an intravenous re-induction with ustekinumab within the 6 months prior to baseline.
Patients with an impassable stenosis even after attempt of endoscopic balloon dilation.
Patients with an abscess
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| Name | Affiliation | Role |
|---|---|---|
| Peter Bossuyt, MD | BIRD (Belgian IBD Research and Development) vzw | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ingrid Arijs | Zaventem | 1930 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41747777 | Derived | Bossuyt P, 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; Vermeire S. The Effect of Dose Intensification After Secondary Loss of Response to Ustekinumab in Crohn's Disease: Results of the REScUE Study. Gastroenterology. 2026 Jul;171(1):99-109. doi: 10.1053/j.gastro.2026.01.042. Epub 2026 Feb 24. |
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Eligible Crohn's Disease patients were treated with ustekinumab at a standard maintenance dose of 90 mg every 8 weeks SC. Patients needed to have a documented primary response to standard IV induction with ustekinumab and a documented secondary loss of response based on Patient-Reported Outcomes and objective documentation of disease activity.
Between February 2020 and October 2023 a total of 132 patients were screened and 108 patients were randomized. First Patient In (FPI) was on 11Mar2020. Last Patient In (LPI) was on 17Oct2023. Last Patient Out (LPO) was on 25Sep2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ustekinumab q4w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44). |
| FG001 | Ustekinumab q8w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ustekinumab q4w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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)] | Posted | Count of Participants | Participants | week 48 |
|
From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ustekinumab q4w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abdominal pain after right hemicolectomy | Injury, poisoning and procedural complications | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ingrid Arijs | Belgian IBD Research and Development (BIRD) | 0499317005 | ingrid.arijs@birdgroup.be |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 9, 2022 | Mar 20, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 1, 2024 | Mar 20, 2026 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069549 | Ustekinumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
Proportion of patients with endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD) <5) at week 48 |
| week 48 |
| Proportion of Patients With Endoscopic Response at Week 48 | Proportion of patients with endoscopic response (≥50% decrease in simple endoscopic score for Crohn's disease (SES-CD)) at week 48 | week 48 |
| Proportion of Patients With Clinical Remission at Week 8 | Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 8 | week 8 |
| Proportion of Patients With Clinical Remission at Week 48 | Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 48 | week 48 |
| Proportion of Patients With Biomarker Remission at Week 48 | Proportion of patients with biomarker remission (C-reactive protein <5 mg/L and fecal calprotectin <250 µg/g) at week 48 | week 48 |
| Proportion of Patients With Serious Adverse Events at Week 48 | Proportion of patients with serious adverse events at week 48 | Week 48 |
| BG001 | Ustekinumab q8w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Ustekinumab q8w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44). |
|
|
|
| Secondary | Proportion of Patients With Complete Endoscopic Remission at Week 48 | Proportion of patients with complete endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD )<3) at week 48 | Posted | Count of Participants | Participants | week 48 |
|
|
|
|
| Secondary | Proportion of Patients With Endoscopic Remission at Week 48 | Proportion of patients with endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD) <5) at week 48 | Posted | Count of Participants | Participants | week 48 |
|
|
|
|
| Secondary | Proportion of Patients With Endoscopic Response at Week 48 | Proportion of patients with endoscopic response (≥50% decrease in simple endoscopic score for Crohn's disease (SES-CD)) at week 48 | Posted | Count of Participants | Participants | week 48 |
|
|
|
|
| Secondary | Proportion of Patients With Clinical Remission at Week 8 | Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 8 | Posted | Count of Participants | Participants | week 8 |
|
|
|
|
| Secondary | Proportion of Patients With Clinical Remission at Week 48 | Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 48 | Posted | Count of Participants | Participants | week 48 |
|
|
|
|
| Secondary | Proportion of Patients With Biomarker Remission at Week 48 | Proportion of patients with biomarker remission (C-reactive protein <5 mg/L and fecal calprotectin <250 µg/g) at week 48 | Posted | Count of Participants | Participants | week 48 |
|
|
|
|
| Secondary | Proportion of Patients With Serious Adverse Events at Week 48 | Proportion of patients with serious adverse events at week 48 | Posted | Count of Participants | Participants | Week 48 |
|
|
|
| 0 |
| 54 |
| 9 |
| 54 |
| 44 |
| 54 |
| EG001 | Ustekinumab q8w | Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44). | 0 | 54 | 7 | 54 | 46 | 54 |
| Cardiac Ablation | Surgical and medical procedures | Systematic Assessment |
|
| Laparoscopic right hemicolectomy | Surgical and medical procedures | Systematic Assessment |
|
| Extensive colitis | Gastrointestinal disorders | Systematic Assessment |
|
| gastro-enteritis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Small bowel ileus | Gastrointestinal disorders | Systematic Assessment |
|
| (sub)obstruction | Gastrointestinal disorders | Systematic Assessment |
|
| Bowel obstruction terminal ileitis | Gastrointestinal disorders | Systematic Assessment |
|
| Flare of Crohn's Disease | Gastrointestinal disorders | Systematic Assessment |
|
| Presacral abscess | Gastrointestinal disorders | Systematic Assessment |
|
| Stricturing Crohn's Disease | Gastrointestinal disorders | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | Systematic Assessment |
|
| Stenosis Hepaticojejunostomia | Hepatobiliary disorders | Systematic Assessment |
|
| Infection Giardia Lamblia | Infections and infestations | Systematic Assessment |
|
| E. Coli urosepsis | Infections and infestations | Systematic Assessment |
|
| electrolyte abnormalities | Metabolism and nutrition disorders | Systematic Assessment |
|
| Stress fracture femoral neck left | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Arthralgia due to infliximab | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Recurrent abdominal wall hernia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| fatigue | General disorders | Systematic Assessment |
|
| gastro-enteritis | Gastrointestinal disorders | Systematic Assessment |
|
| Worsening of Crohn's Disease | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Skin abnormalities | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| psychiatric symptoms | Psychiatric disorders | Systematic Assessment |
|
| musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| respiratory infection | Infections and infestations | Systematic Assessment |
|
| flu | Infections and infestations | Systematic Assessment |
|
| lab abnormalities/deficiencies | Metabolism and nutrition disorders | Systematic Assessment |
|
According to the clinical study agreement, the sponsor owns the study data and prepares the study report. Investigators must comply with confidentiality and publication provisions, which remain in effect after completion of the study.
| D007410 | Intestinal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |