The purpose of this study is to evaluate the efficacy and safety of JNJ-64304500 as add-on therapy to standard of care (SOC) biologic treatment with anti-tumor necrosis factor alpha or anti-interleukin 12/23 inhibitors in participants with active Crohn's disease in response but not remission to SOC biologic therapy.
Biologic agents such as anti-tumor necrosis factor (TNF) and interleukin (IL)-12/23 antagonists have become the standard of care (SOC) in the treatment of patients with Crohn's disease. However, many patients fail to fully respond to treatment. This study will evaluate the efficacy of 10 week add on treatment with JNJ-64304500, compared to placebo, in patients taking SOC anti-TNF or anti-IL12/23 biologics. The study consists of a screening phase (up to 8 weeks); treatment phase (up to 12 weeks and follow-up phase (up to 16 weeks after the last administration of study agent). The total study duration will be up to 34 weeks. Key safety assessments include adverse events, clinical laboratory tests (hematology and chemistry), vital signs, monitoring for injection-site and hypersensitivity reactions, and early detection of active tuberculosis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
JNJ-64304500 will be administered as SC injection.
Matching placebo will be administered as SC injection.
Adalimumab will be administered as SOC biological therapy.
Medisphere Medical Research Center, Llc
Evansville, Indiana, United States
Number of Participants with Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs)
An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. TEAEs are AEs with onset during the intervention phase or that are a consequence of a preexisting condition that has worsened since baseline.
Time frame: Up to Week 26
Number of Participants with Treatment-emergent Serious Adverse Events (SAEs)
TEAEs are AEs with onset during the intervention phase or that are a consequence of a preexisting condition that has worsened since baseline. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Time frame: Up to Week 26
Number of Participants with TEAEs by System Organ Class with a Frequency Threshold of 5 Percent (%) or More
Number of participants with TEAEs by system organ class with a frequency threshold of 5 % or more will be reported.
Time frame: Up to Week 26
Number of Participants with Infections, Serious Infections and Infections Requiring Antimicrobial Treatment
Number of participants with infections, serious infections and infections requiring antimicrobial treatment will be reported.
Time frame: Up to Week 26
Number of Participants with Clinically Significant Abnormalities in Vital Signs
Number of participants with clinically significant abnormalities in vital signs will be reported.
Time frame: Up to Week 26
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Ustekinumab will be administered as SOC biological therapy.
Number of Participants with Clinically Significant Abnormalities in Laboratory Tests
Number of participants with clinically significant abnormalities in laboratory tests will be reported.
Time frame: Up to Week 26
Number of Participants with AEs Leading to Treatment Discontinuation
Number of participants with AEs leading to treatment discontinuation will be reported.
Time frame: Up to Week 26
Change from Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12
Change from baseline in the CDAI score at Week 12 will be reported. CDAI will be assessed by collecting information on 7 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid or very soft stools, abdominal pain/cramping and general well-being) with scores ranging from 0 to approximately 600. The last 4 variables are scored over 7 days by the participant in a diary. A decrease in CDAI over time indicates improvement in disease activity.
Time frame: Baseline and Week 12
Percentage of Participants Achieving Clinical Response
Percentage of participants achieving a clinical response as measured by CDAI score (including greater than or equal to \[\>=\] 50, \>=70, \>=100, and \>=150 point reduction from baseline in CDAI) will be reported.
Time frame: Week 12
Percentage of Participants Achieving Clinical Remission
Percentage of participants achieving a clinical remission as measured by CDAI score (CDAI less than \[\<\] 150) will be reported.
Time frame: Week 12
Change from Baseline in the Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12
Change from baseline in the SES-CD score at Week 12 will be reported. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 56).
Time frame: Baseline and Week 12
Percentage of Participants Achieving an Endoscopic Response
Percentage of participants achieving an endoscopic response defined as at least a 50% improvement from baseline in the SES-CD.
Time frame: Week 12
Percentage of Participants Achieving an Endoscopic Remission
Percentage of participants achieving an endoscopic remission defined as an SES-CD score less than or equal to (\<=) 2.
Time frame: Week 12
Change From Baseline in Abdominal Pain (AP)
Change in AP from baseline based on a 0 to 10 numerical rating scale (NRS) will be reported. A score of 0 represents "no abdominal pain" and a score of 10 represents the "worst possible AP," with greater scores indicating greater pain severity and intensity.
Time frame: Baseline up to Week 12
Percentage of Participants Achieving Patient-Reported Outcome (PRO)-2 Remission
Percentage of participants achieving a PRO-2 remission defined as AP mean daily score (AP component of the CDAI score) at or below 1 and stool frequency (SF) mean daily score at or below 3, that is, AP \<=1 and SF \<=3.
Time frame: Week 12
Serum Concentrations of JNJ-64304500
Serum concentrations of JNJ-64304500 will be reported.
Time frame: Up to Week 26
Number of Participants with Antibodies to JNJ-64304500
Antibody titers binding to JNJ-64304500 in positive samples will be reported.
Time frame: Up to Week 26
Number of Participants with Neutralizing Antibodies to JNJ-64304500
Number of participants receiving at least one dose of JNJ-64304500 with neutralizing antibodies to JNJ-64304500 will be summarized.
Time frame: Up to Week 26
Change in Pharmacodynamics (PD) Biomarker Levels of C-Reactive Protein (CRP) from Baseline Compared with Placebo
Change in PD biomarker levels of CRP from baseline compared with placebo will be reported.
Time frame: Baseline, up to Week 26
Change in PD Biomarker Levels of Fecal Calprotectin from Baseline Compared with Placebo
Change in PD biomarker levels of fecal calprotectin from baseline compared with placebo will be reported.
Time frame: Baseline, up to Week 26
Change in PD Biomarker Levels of Fecal Lactoferrin from Baseline Compared with Placebo
Change in PD biomarker levels of fecal lactoferrin from baseline compared with placebo will be reported.
Time frame: Baseline, up to Week 26