Efficacy and safety of a combination therapy of Guselkumab and Golimumab in participants with moderately to severely active ulcerative colitis
Résumé de l'étude
The study aims to determine whether the combination of Guselkumab and Golimumab is safe and effective in treating patients with moderately to severely active ulcerative colitis. Treatment with three different doses of the combination therapy will be 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 (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 know 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 a medium or high dose. Participation in the long-term extension depends on whether symptoms have improved during the first year of treatment.
(BASEC)
Intervention étudiée
The total study duration is up to 256 weeks, of which 48 weeks of combination therapy with Guselkumab/Golimumab (currently called "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: 12 weeks after the last dose of study treatment. At the visit in week 0, eligible participants will be randomly assigned in a 1:2:2:2:2:2 ratio to one of the following groups (randomized) and will receive an injection under the skin (subcutaneous) 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 responded adequately to treatment by week 24 will start a combination therapy with a medium or high dose 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 Group 4 (high dose JNJ-78934804 group) and Group 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 have 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 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)
Maladie en cours d'investigation
moderately to severely active ulcerative colitis
(BASEC)
1. Age 18 to 65 years inclusive (at the time of consent) 2. Documented diagnosis of ulcerative colitis (UC) (based on tissue examinations (histological) and either by endoscopy (endoscopic) or imaging techniques (radiographic)) ≥ 12 weeks prior to screening. A biopsy report supporting the diagnosis must be present in the source documents. 3. Moderately to severely active UC, defined as follows: a.) Modified Mayo score (scoring system to assess the severity of UC) of 5 to 9 inclusive at week 0, calculated based on the Mayo endoscopy subscores obtained during the central review of video endoscopy at screening AND b.) Endoscopy subscore > 2 at screening, using the final endoscopy subscores obtained during the central review of video endoscopy at screening. 4. The patient has previously shown no initial response to at least one therapy at an approved dose for the treatment of UC (i.e., Infliximab, Adalimumab, Vedolizumab, Ustekinumab, Tofacitinib, Filgotinib, Upadacitinib, Ozanimod or approved corresponding biosimilars) (i.e., primary non-responder), has initially responded but lost response with continued therapy (i.e., secondary non-responder) or has shown intolerance reactions and has a documented history. 5. The results of laboratory tests at screening must be within the ranges defined in the study protocol. (BASEC)
Critères d'exclusion
1. Severe extensive colitis (according to criteria defined in the study protocol) 2. UC limited to the rectum or to less than 20 cm from the anal canal 3. Presence of a stoma 4. Presence or history of a fistula 5. History of extensive bowel resection (i.e., less than 30 cm of remaining colon), which would prevent adequate assessment of the effect of the study treatment on clinical disease activity 6. Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease 7. Known allergies, hypersensitivity, or intolerance to Guselkumab or any of its other components, Golimumab or any of its other components, or Guselkumab/Golimumab combination or any of its other components. 8. Known history, in the opinion of the investigator, of inadequate response to Guselkumab, if it has already been used as off-label therapy for UC, or to Golimumab 9. Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study or within 6 months after the last dose of study treatment 10. Known or existing chronic or recurrent infection 11. Known active tuberculosis (TB) or untreated, not yet acute (latent) TB 12. Existing malignant disease or known malignant disease in the last 5 years prior to screening 13. Known disease in which there is excess production of white blood cells (lymphocytes) (lymphoproliferative) or signs and symptoms indicating a possible lymphoproliferative disease 14. Known or existing inadequate heart pump function (congestive heart failure), including medically controlled congestive heart failure without symptoms (asymptomatic). 15. Severe progressive or uncontrolled organ/system dysfunction. (BASEC)
Lieu de l’étude
Bâle, Berne, St-Gall, Zurich
(BASEC)
Sponsor
Janssen-Cilag International NV, Beerse, Belgien Janssen-Cilag AG, Zug, Switzerland
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Prof. Dr. med. Frank Seibold
+41 31 302 32 34
studien.seibold@clutterintesto.chIntesto - Gastroenterologische Praxis, Crohn-Colitis-Zentrum, Bremgartenstrasse 119, 3012 Bern, Schweiz
(BASEC)
Informations générales
Janssen Research & Development, LLC
(ICTRP)
Informations scientifiques
Janssen Research & Development, LLC
(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Berne
(BASEC)
Date d'approbation du comité d'éthique
08.08.2023
(BASEC)
Identifiant de l'essai ICTRP
NCT05242484 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
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 Ulcerative Colitis (BASEC)
Titre académique
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 Ulcerative Colitis (ICTRP)
Titre public
A Study of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis (ICTRP)
Maladie en cours d'investigation
Colitis, Ulcerative (ICTRP)
Intervention étudiée
Biological: GuselkumabBiological: GolimumabBiological: JNJ-78934804Drug: Placebo (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Confirmed diagnosis of ulcerative colitis (UC) for at least 3 months prior to
baseline
- Moderately to severely active UC as assessed by the modified Mayo score
- Demonstrated inadequate response, loss of response, or intolerance to at least one
biologic or novel oral with biologic-like activity
- If female and of childbearing potential, must meet the contraception and
reproduction requirements
Exclusion Criteria:
- Has severe extensive colitis as defined in the protocol
- Extent of inflammatory disease limited to the rectum
- Participants with current diagnosis of indeterminate colitis, microscopic colitis,
ischemic colitis, or Crohn's disease (CD)
- Has a history of, or ongoing, chronic or recurrent infectious disease, including but
not limited to, sinopulmonary infections, bronchiectasis, recurrent renal/urinary
tract infections (example, pyelonephritis, cystitis), an open, draining, or infected
skin wound, or an ulcer
- Currently has a malignancy or a history of malignancy within 5 years before
screening (with the exception of nonmelanoma skin cancer or cervical carcinoma in
situ that has been treated with no evidence of recurrence within 12 months of first
dose of study intervention) (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Percentage of Participants with Clinical Remission at Week 48 (ICTRP)
Percentage of Participants with Endoscopic Improvement at Week 48;Percentage of Participants with Corticosteroid-free Clinical Remission at Week 48;Percentage of Participants with Symptomatic Remission at Week 48;Percentage of Participants with Combination of Histological Remission and Endoscopic Improvement at Week 48;Secondary Comparison: Percentage of Participants with Clinical Remission at Week 48;Percentage of Participants with Adverse Events (AEs);Percentage of Participants with Serious Adverse Events (SAEs);Laboratory Parameters Over Time;Vital Signs 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)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC (ICTRP)
ID secondaires
78934804UCO2001, 2021-005528-39, 2023-504743-13-00, CR109179 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT05242484 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible