Efficacy and Safety Evaluation of Guselkumab and Golimumab Combination Therapy in Moderate to Severe Crohn's Disease: A Phase 2b Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of JNJ-78934804 at Week 48 in comparison to each monotherapy, specifically **guselkumab** alone and **golimumab** alone, in participants with moderately to severely active **Crohn's Disease**. This evaluation is clinically relevant as it aims to determine the potential benefits of combination therapy over standard monotherapy treatments, which could lead to improved management strategies for patients suffering from this chronic inflammatory bowel disease.

The clinical trial involves a total of **663 participants** diagnosed with **Moderately to Severely Active Crohn's Disease**. 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 Crohn's disease for at least three months prior to baseline, with moderate to severe activity as assessed by the Crohn's Disease Activity Index (CDAI), stool frequency, abdominal pain score, and simple endoscopic score for Crohn's disease (SES-CD). The trial population includes individuals who have demonstrated an inadequate response, loss of response, or intolerance to at least one advanced therapy for inflammatory bowel disease, which includes biologics and oral small molecule therapies with biologic-like effects. Both genders are represented, and the study includes vulnerable populations. Lifestyle considerations such as diet, physical activity, and habits were not specified by the sponsor.

The clinical trial is designed as a **Phase 2b randomized, double-blind, active- and placebo-controlled, parallel-group, multicenter study**. The primary objective is 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**. The trial aims to assess the efficacy of JNJ-78934804 at Week 48 compared with each monotherapy (guselkumab alone and golimumab alone). The study is expected to run from February 2023 to March 2029, with a total duration of approximately six years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of Crohn's disease for at least three months prior to baseline and a confirmed diagnosis of moderate to severe Crohn's 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 occur at Week 48, where the primary endpoint of clinical remission and endoscopic response will be evaluated.

The expected length of participant involvement is up to 48 weeks, with conditions for early termination including inadequate response, loss of response, or intolerance to the treatment. Participants will receive either the combination therapy, monotherapy, or placebo, administered via subcutaneous injection using a pre-filled syringe. The study will utilize the UltraSafe Plus™ Passive Needle Guard to facilitate self-injection and ensure safety. The trial will adhere to strict eligibility criteria, including the requirement for female participants of childbearing potential to meet specific contraception and reproduction requirements.

The clinical trial involves the administration of several treatments, including the experimental medication **JNJ-78934804**. This medication is a **solution for injection in a pre-filled syringe** and contains the active substances **guselkumab** and **golimumab**. It is administered via **subcutaneous use**. The dosing schedule is designed for a maximum treatment period of 240 days, although specific dosage amounts are not provided. The administration is facilitated by the UltraSafe Plus™ Passive Needle Guard, which aids in self-injection and ensures safety by activating a needle guard post-delivery.

Another treatment in the study is **Guselkumab**, provided as a **solution for injection in a pre-filled syringe** with a concentration of 100 mg/mL. This medication is also administered subcutaneously and is supported by the UltraSafe Plus™ Passive Needle Guard for safe self-administration. The treatment period is similarly capped at 240 days, with no specific daily or total dose amounts detailed.

**Golimumab** is also included in the trial as a **solution for injection in a pre-filled syringe**. Like the other treatments, it is administered subcutaneously and utilizes the UltraSafe™ Passive Needle Guard to facilitate safe injection. The treatment duration is up to 240 days, with unspecified dosage details.

The study also employs a **placebo** for Guselkumab, Golimumab, and JNJ-78934804. The placebo is used to maintain the double-blind nature of the trial, ensuring unbiased results. The pharmaceutical form, dosage, and administration route of the placebo are not specified, aligning with the standard practice of matching the experimental treatments' administration characteristics.

The efficacy of the combination therapy with **guselkumab** and **golimumab** in participants with moderately to severely active Crohn's Disease will be assessed in this Phase 2b clinical trial. The primary endpoint for evaluating efficacy is the achievement of clinical remission and endoscopic response at Week 48, compared with each monotherapy. Efficacy will be measured using the Crohn's Disease Activity Index (CDAI), stool frequency (SF), abdominal pain (AP) score, and the Simple Endoscopic Score for Crohn's Disease (SES-CD). These parameters will be collected and analyzed at specified timepoints, with the primary focus on Week 48.