Evaluation of Guselkumab and Golimumab Combination Therapy Efficacy and Safety in Moderate to Severe Ulcerative Colitis: A Phase 2b Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of the combination therapy JNJ-78934804 at Week 48 in comparison to each monotherapy, specifically **guselkumab** alone and **golimumab** alone, in participants with moderately to severely active **ulcerative colitis**. This evaluation is clinically relevant as it aims to determine the potential benefits of combination therapy over standard monotherapy treatments, potentially offering improved therapeutic outcomes for patients suffering from this chronic inflammatory bowel disease.

The clinical trial involves a total of **369 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants were selected based on a confirmed diagnosis of ulcerative colitis for at least three months prior to baseline and must have demonstrated an inadequate response, loss of response, or intolerance to at least one advanced therapy for inflammatory bowel disease. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified. The selection criteria ensure that participants have a history of moderately to severely active ulcerative colitis as assessed by the modified Mayo score. Female participants of childbearing potential are required to meet specific contraception and reproduction requirements.

The clinical trial is designed to evaluate the efficacy and safety of combination therapy with **guselkumab** and **golimumab** in participants with moderately to severely active **ulcerative colitis**. This is a Phase 2b, randomized, double-blind, active- and placebo-controlled, parallel-group, multicenter study. The trial aims to assess the induction and maintenance of combination therapy over a period of 48 weeks, with the primary endpoint being clinical remission at Week 48 compared with each monotherapy. The study is expected to conclude by March 2029, with recruitment having commenced in January 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a confirmed diagnosis of ulcerative colitis for at least three months prior to baseline and a history of inadequate response or intolerance to advanced therapy for inflammatory bowel disease. The trial will include follow-up visits to monitor the participants' response to the treatment and any adverse effects. The end-of-study visit will assess the overall outcomes and safety of the treatment regimen.

The expected length of participant involvement is approximately 48 weeks, aligning with the primary endpoint assessment. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial employs a rigorous methodology to ensure the reliability and validity of the results, with the use of placebo and active comparators to evaluate the efficacy of the combination therapy. Participants will receive the study medication via subcutaneous injection, facilitated by devices such as the UltraSafe™ Passive Needle Guard, which ensures safe and effective administration.

**Golimumab** is administered as a **solution for injection in a pre-filled syringe**. The pharmaceutical form is designed for **subcutaneous use**. The medication is provided by Janssen-Cilag International N.V. and is identified by the sponsor product code CNTO138. The active substance, golimumab, is a protein of non-specified origin. The treatment period for golimumab is up to 240 weeks, with the dosing schedule and frequency determined by the study protocol. The administration device includes the UltraSafe™ Passive Needle Guard (PFS-U), which facilitates self-injection and ensures passive activation of the needle guard post-delivery.

The **placebo** used in this study is designed to match the appearance and administration route of the active treatments, including guselkumab, golimumab, and JNJ-78934804. The placebo is utilized to maintain the double-blind nature of the trial and is administered in a manner consistent with the active treatments, although specific pharmaceutical form details are not applicable.

**Guselkumab** is provided as a **solution for injection in a pre-filled syringe** with a concentration of 100 mg/mL. It is administered via **subcutaneous injection**. The product is manufactured by Janssen-Cilag International N.V. and is identified by the sponsor product code CNTO 1959. The active substance, guselkumab, is a protein of non-specified origin. The treatment duration is up to 240 weeks, with dosing schedules outlined in the study protocol. The administration device includes the UltraSafe Plus™ Passive Needle Guard (PFS-U), which aids in self-injection and ensures passive activation of the needle guard after delivery.

**JNJ-78934804** is a combination therapy containing both **guselkumab and golimumab**. It is administered as a **solution for injection in a pre-filled syringe** for **subcutaneous use**. The product is provided by Janssen-Cilag International N.V. and is identified by the sponsor product code JNJ-78934804. Both active substances are proteins of non-specified origin. The treatment period extends up to 240 weeks, with specific dosing schedules detailed in the study protocol. The administration device is the UltraSafe Plus™ Passive Needle Guard (PFS-U), which facilitates self-injection and ensures passive activation of the needle guard post-delivery.

The efficacy of the combination therapy with **Guselkumab** and **Golimumab** in participants with moderately to severely active ulcerative colitis will be assessed in this Phase 2b clinical trial. The primary endpoint for evaluating efficacy is clinical remission at Week 48, compared with each monotherapy. The trial is designed as a randomized, double-blind, active- and placebo-controlled, parallel-group, multicenter study. Participants will be evaluated for clinical remission using the modified Mayo score, which is a validated scale for assessing disease activity in ulcerative colitis. The trial aims to determine the efficacy of the combination therapy at Week 48, providing a comparative analysis against the monotherapies of **Guselkumab** and **Golimumab** alone. The study will involve the use of pre-filled syringes for subcutaneous administration, facilitated by devices such as the UltraSafe™ Passive Needle Guard and UltraSafe Plus™ Passive Needle Guard, which ensure safe and effective delivery of the medication. The trial is expected to conclude by March 2029, with recruitment having started in January 2023.