Effectiveness and Safety of Ustekinumab Intensification in Crohn's Disease
Study Details
Study Description
Brief Summary
The primary purpose of this study is to evaluate the efficacy and safety of intravenous reinduction or intravenous administration at regular intervals of ustekinumab in participants with loss of response to standard regimen.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Detailed Description
This study evaluates the efficacy and safety of intravenous reinduction or intravenous administration at regular intervals of ustekinumab. It consists of escalation treatment period (Week 0 to 52); and safety follow up visit (24 weeks after last dose). Study assessments will include Harvey-Bradshaw index (HBI), Physician Global Assessment Score (PGA), laboratory evaluations, endoscopic evaluation, review of concomitant medications and adverse events (AEs).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| intravenous reinduction Participants who experience a loss of response to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg. Participants will resume their standard therapy after reinduction. |
Drug: Ustekinumab
Patients will receive an intravenous induction (adjusted 6 mg/kg dose) followed by subcutaneous 90 mg every 12 or 8 weeks, and will receive dose escalation when response is not effective enough.
Other Names:
|
| intravenous administration q8w Participants who experience a loss of response to 90 mg ustekinumab maintenance treatment will receive ustekinumab intravenously at regular interval (every 8 weeks). |
Drug: Ustekinumab
Patients will receive an intravenous induction (adjusted 6 mg/kg dose) followed by subcutaneous 90 mg every 12 or 8 weeks, and will receive dose escalation when response is not effective enough.
Other Names:
|
| intravenous administration q4w or q6w Participants who experience a loss of response to 90 mg ustekinumab maintenance treatment will receive ustekinumab intravenously at shorten interval (every 4 weeks or every 6 weeks). |
Drug: Ustekinumab
Patients will receive an intravenous induction (adjusted 6 mg/kg dose) followed by subcutaneous 90 mg every 12 or 8 weeks, and will receive dose escalation when response is not effective enough.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of participants with steroid-free clinical remission at Week 24 [Week24]
Percentage of participants with steroid-free clinical remission at Week 24 from the escalation will be assessed. Steroid-free clinical remission (performed only in patients on prednisone or budesonide at time of initiation of UST) was defined as tapering off steroids completely and HBI ≤ 4 points or complete resolution in CD symptoms or severity assessed by PGA.
Secondary Outcome Measures
- Percentage of participants with clinical response at week 16 [Week 16]
Percentage of participants with corticosteroid-free clinical response at Week 16 from the escalation will be assessed. Clinical response was defined as a reduction of at least 3 points in HBI compared to baseline or 50% reduction in CD symptoms or severity assessed by Physician Global Assessment (PGA).
- Percentage of participants with biochemical remission at Week 24 [Week 24]
Percentage of participants with biochemical remission at Week 24 from the escalation will be assessed. Biochemical remission was defined as a CRP concentration ≤5 mg/L and a FCP level of ≤200 µg/g.
- Percentage of participants with endoscopic remission at Week 52 [Week 52]
Percentage of participants with endoscopic remission at Week 52. Endoscopic remission was defined as SES-CD ≤3 or absence of ulcers or described as the absence of ulceration.
- Percentage of participants with clinical remission at week 52 [Week 52]
Percentage of participants with clinical remission at week 52 from the escalation will be assessed. Clinical remission was defined as HBI ≤ 4 points or complete resolution in CD symptoms or severity assessed by PGA.
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [up to 1.5 years]
The percentage of participants with at least one adverse event and subcategories of adverse events will be assessed. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
- Percentage of Participants with Infections and Serious Infections [up to 1.5 years]
Percentage of participants with infections and serious infections will be reported.
- Percentage of Participants discontinue UST [up to 1.5 years]
Proportion of patients who discontinue UST and start new biotherapy during the follow-up will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Agree to participate in the study
-
With active Crohn's disease
-
Patients undergoing UST dose intensification were either received intravenous ustekinumab at regular intervals or, alternatively, received an intravenous reinduction (6 mg/kg) instead of a scheduled SC dose at the discretion of the treating physician
Exclusion Criteria:
-
who had received ustekinumab for an indication
-
pregnant or nursing
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
- Principal Investigator: Yan Chen, MD, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023-0004