A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease

Study Purpose

The primary purpose of this study is to evaluate the efficacy and safety of a single intravenous (IV) re-induction dose of approximately 6 milligram per kilogram (mg/kg) ustekinumab in participants with secondary loss of response (LoR) to subcutaneous (SC) every 8 Weeks (q8w) 90 mg ustekinumab maintenance therapy.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion criteria:

- A history of Crohn's disease or fistulizing Crohn's disease of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy - Currently receiving subcutaneous 90 mg every 8 weeks (q8w) ustekinumab maintenance therapy and initially responded to ustekinumab induction therapy, administered according to the local label, followed by secondary loss of response (LoR) to ustekinumab.

Secondary LoR to ustekinumab is defined as active disease at study baseline, proven by a Crohn's Disease Activity Index (CDAI) score of greater than or equal to (>=) 220 and <=450 with at least one of the following: Elevated C-reactive protein (CRP) (>3.0 milligram per liter [mg/L]); and/or elevated Fecal calprotectin (FeCa) >250 milligram per kilogram [mg/kg]); and/or endoscopy (performed less than or equal to (<=) 3 months before baseline) with evidence of active Crohn's disease, (defined as one or more ulcerations in the ileum and/or colon)

- Participants receiving either oral 5-aminosalicylic acid (5-ASA) compounds, oral corticosteroids (for example {e.g.}, prednisone, budesonide) at a prednisone-equivalent dose of <=40 mg/day or <=9 mg/day of budesonide, antibiotics used as the primary treatment of Crohn's disease, or conventional immunomodulators (i.e., azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) are permitted providing the doses indicated are stable before baseline or have been discontinued before baseline within the protocol defined durations
Exclusion Criteria:
- Complications of Crohn's disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab - Currently has or is suspected to have an abscess.

Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks before baseline (or 8 weeks before baseline for intra-abdominal abscesses) provided there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified - Any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline - A draining (i.e., functioning) stoma or ostomy - Received any off-label use of ustekinumab, including additional intravenous (IV) re-induction or shortened frequency of subcutaneous dose administration after the initial weight-tiered based IV induction dose of ustekinumab

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03782376
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Janssen-Cilag Ltd.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Janssen-Cilag Ltd. Clinical Trial
Principal Investigator Affiliation	Janssen-Cilag Ltd.
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Austria, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Crohn Disease
Study Website:	View Trial Website

Additional Details

This study compares the efficacy and safety of a single weight-tiered based IV re-induction dose of approximately 6 mg/kg ustekinumab versus continuing with regular SC q8w 90 mg ustekinumab administration. It consists of screening (5 weeks); treatment period (Week 0 to 24); and safety follow up visit (20 weeks after last dose). The primary hypothesis is that a single IV re-induction dose of ustekinumab is superior to continuing with regular SC q8w maintenance treatment as measured by clinical response after 16 weeks of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy, patient-reported outcomes (PROs), laboratory evaluations, biomarkers, review of concomitant medications and adverse events (AEs), and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants will be randomly assigned to receive either ustekinumab IV re-induction or regular SC q8w 90 mg ustekinumab injection at baseline in a double dummy design. No participants will be treated with placebo only.

Arms & Interventions

Arms

Experimental: Group 1: Ustekinumab (IV re-induction)

Participants who experience a secondary loss of response (LoR) 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 and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.

Active Comparator: Group 2: Ustekinumab (Continuous q8w SC maintenance)

Participants who experience a secondary LoR to 90 mg ustekinumab maintenance treatment, administered subcutaneously q8w will receive ustekinumab 90 mg subcutaneously and matching placebo intravenously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.

Interventions

Drug: - Ustekinumab approximately 6 mg/kg (IV)

Participants will receive ustekinumab approximately 6mg/kg intravenously at Week 0.

Drug: - Placebo (SC)

Participants will receive SC injection of placebo at Week 0.

Drug: - Placebo (IV)

Participants will receive IV infusion of placebo at Week 0.

Drug: - Ustekinumab 90 mg (SC) Group 1

Participants will receive SC injection of ustekinumab 90 mg at Weeks 8 and 16.

Drug: - Ustekinumab 90 mg (SC) Group 2

Participants will receive SC injection of ustekinumab 90 mg at Weeks 0, 8 and 16.

Contact a Trial Team

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University of California, San Diego, La Jolla, California

Status

Recruiting

Address

University of California, San Diego

La Jolla, California, 92093

Site Contact

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