Efficacy and safety of a combination therapy of Guselkumab and Golimumab in participants with moderately to severely active Crohn's disease
Zusammenfassung der Studie
The study aims to determine whether the combination of Guselkumab and Golimumab is safe and effective in treating patients with moderately to severely active Crohn's disease. The treatment with three different doses of the combination therapy is compared to treatment with Guselkumab or Golimumab alone (i.e., not in combination). This study includes 3 different phases: Screening phase (up to 8 weeks), treatment phase (48 weeks), and optional long-term extension phase (up to 192 weeks). Study participants will be randomly assigned to one of a total of 6 study groups and will receive the corresponding treatment from week 0 to week 20 (description of groups see "Investigated Intervention"). Some patients will receive placebo along with an active drug so that the number of injections in all treatment groups is the same. Neither the patients themselves nor the investigator knows which investigational product the patient receives. This procedure is called blinding. Depending on the response up to the visit in week 24, the investigator will decide whether to continue the current treatment or start a combination therapy with medium or high dose. Participation in the long-term extension phase depends on whether symptoms have improved during the first year of treatment.
(BASEC)
Untersuchte Intervention
The total study duration is up to 256 weeks, of which 48 weeks of combination therapy with Guselkumab/Golimumab (currently referred to as JNJ-78934804) will be evaluated.
The study consists of the following phases:
• Screening phase: up to 8 weeks
• Main treatment phase: 48 weeks (last dose 4 weeks before the end of the main treatment phase)
• Optional long-term extension phase: 192 weeks (last dose 4 weeks before the end of the long-term extension phase)
• Safety follow-up phase: up to 12 weeks after the last dose of the study treatment
At the visit in week 0, eligible participants will be randomly assigned in a ratio of 1:2:2:2:2:2 to one of the following groups (randomized) and will receive a subcutaneous injection every 4 weeks:
• Group 1: receives a substance without active ingredient (placebo)
• Group 2: receives an active treatment with Guselkumab alone (monotherapy)
• Group 3: receives an active treatment with Golimumab alone (monotherapy)
• Group 4: receives an active treatment with a high dose of JNJ-78934804
• Group 5: receives an active treatment with a medium dose of JNJ-78934804
• Group 6: receives an active treatment with a low dose of JNJ-78934804
Participants who have not adequately responded to treatment by week 24 will begin a combination therapy based on their initial assignment:
• Participants in group 1 (placebo group), group 2 (Guselkumab monotherapy group), group 3 (Golimumab monotherapy group), and group 6 (low dose JNJ-78934804 group) will receive an induction and maintenance therapy with a medium dose of JNJ-78934804
• Participants in groups 4 (high dose JNJ-78934804 group) and 5 (medium dose JNJ-78934804 group) will receive an induction and maintenance therapy with a high dose of JNJ-78934804.
Participants who discontinue the study treatment before week 48 will attend an early discontinuation visit (Early Discontinuation, ED) before the end of their study participation. All randomized and treated participants must attend the safety follow-up visit 12 weeks after the last dose of the study treatment.
All participants who have achieved a clinical response at week 48 compared to week 0 and who, in the opinion of the investigator, continue to benefit from the study treatment may enter a 4-year long-term extension phase (Long-Term Extension, LTE).
(BASEC)
Untersuchte Krankheit(en)
moderately to severely active Crohn's disease
(BASEC)
- Age 18 to 65 years inclusive (at the time of consent) - Crohn's disease (CD) or fistulizing CD for at least 3 months (defined as at least 12 weeks) with intestinal inflammation (colitis), inflammation in the ileum (ileitis), or inflammation at the junction of the colon and small intestine (ileocolitis), confirmed at any time in the past by imaging (radiographic), by tissue sample (histological), and/or by endoscopy (endoscopic) - Clinically active CD, defined as a baseline CDAI score (Crohn's Disease Activity Index, scoring system for clinical assessment of the severity of CD) ≥ 220, but ≤ 450, and either: a. average daily stool frequency ≥ 4 OR b. average daily AP score ≥ 2 (average daily abdominal pain) - Endoscopically proven active ileal (in the ileum) and/or colonic (in the colon) CD, assessed by central endoscopic findings during the screening endoscopy, defined as SES-CD (Simple Endoscopic Score for Crohn's Disease) ≥ 6 at screening (for participants with colonic or ileocolonic disease) or ≥ 4 (for participants with isolated ileal disease) - No initial response (i.e., primary non-responder), initial response that was lost during treatment (i.e., secondary non-responder) or intolerance to one or more ADT (advanced therapies = novel therapies) at a dose approved for the treatment of CD (i.e., Infliximab, Adalimumab, Certolizumab pegol, Vedolizumab, Ustekinumab or approved corresponding biosimilars) - The laboratory results of the screening are within the ranges specified in the study protocol (BASEC)
Ausschlusskriterien
- Complications of CD, such as symptomatic strictures or stenoses (obstructions), short bowel syndrome, or other manifestations that may require surgical intervention, excluding or complicating the assessment of treatment efficacy - Diverting (i.e., functioning) stoma or stoma (artificial anus) - Known allergies, hypersensitivities, or intolerances to Guselkumab, Golimumab, Guselkumab/Golimumab combination (JNJ-78934804) or any of the excipients - In the opinion of the investigator, inadequate response to Guselkumab or Golimumab if these have previously been used as non-approved therapy for CD - Pregnancy or breastfeeding - Chronic or recurrent infectious diseases in the history or ongoing - Active or untreated latent tuberculosis in the history - Malignant diseases or malignant diseases in the history within 5 years prior to screening (BASEC)
Studienstandort
Basel, Bern, St Gallen, Zürich
(BASEC)
Sponsor
Janssen-Cilag International NV Janssen-Cilag AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Prof. Dr. med. Frank Seibold
+41 31 302 32 34
studien.seibold@clutterintesto.chIntesto, Gastroenterologische Praxis - Crohn-Colitis-Zentrum
(BASEC)
Allgemeine Auskünfte
Janssen Research & Development, LLC
(ICTRP)
Wissenschaftliche Auskünfte
Janssen Research & Development, LLC
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
08.08.2023
(BASEC)
ICTRP Studien-ID
NCT05242471 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A Phase 2b Randomized, Double-blind, Active- and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Induction and Maintenance Combination Therapy with Guselkumab and Golimumab in Participants with Moderately to Severely Active Crohn’s Disease (BASEC)
Wissenschaftlicher Titel
A Phase 2b Randomized, Double-blind, Active-and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Induction and Maintenance Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Crohn's Disease (ICTRP)
Öffentlicher Titel
A Study of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Crohn's Disease (ICTRP)
Untersuchte Krankheit(en)
Crohn's Disease (ICTRP)
Untersuchte Intervention
Biological: GuselkumabBiological: GolimumabBiological: JNJ-78934804Drug: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
- Diagnosis of Crohn's disease (CD) for at least 3 months prior to baseline
- Confirmed diagnosis of moderate to severe CD as assessed by Crohn' (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Percentage of Participants with Clinical Remission at Week 48;Percentage of Participants with Endoscopic Response at Week 48 (ICTRP)
Percentage of Participants with Patient-reported Outcomes (PRO)-2 Remission at Week 48;Percentage of Participants with Endoscopic Remission at Week 48;Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 48;Secondary Comparison: Percentage of Participants with Clinical Remission at Week 48;Secondary Comparison: Percentage of Participants with Endoscopic Response at Week 48;Percentage of Participants with Adverse Events (AEs);Percentage of Participants with Serious Adverse Events (SAEs);Clinical Laboratory Parameters Over Time;Vital Sign Parameters Over Time;Suicidal Ideation Assessment Using Columbia Suicide Severity Rating Scale (C-SSRS) Score;Serum Concentrations of Guselkumab Over Time;Serum Concentrations of Golimumab Over Time;Percentage of Participants with Antibodies to Guselkumab;Titers of Antibodies to Guselkumab;Percentage of Participants with Antibodies to Golimumab;Titers of Antibodies to Golimumab;Percentage of Participants with Neutralizing Antibodies to Guselkumab.;Percentage of Participants with Neutralizing Antibodies to Golimumab (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC (ICTRP)
Sekundäre IDs
78934804CRD2001, 2021-003314-39, 2023-504741-32-00, CR109178 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT05242471 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar