Trial results for guselkumab in participants with moderately to severely active Crohn's disease were posted on ClinicalTrials.gov on 2025-05-07. The study showed that various guselkumab dosing regimens led to significant reductions in the Crohn's Disease Activity Index (CDAI) score, with one regimen achieving a mean reduction of -159.8 units compared to -34.4 units for placebo at Week 12. Additionally, up to 54.8% of guselkumab-treated participants achieved both clinical response at Week 12 and clinical remission at Week 48.
Background
Guselkumab is an investigational treatment being evaluated for its efficacy and safety in individuals with moderately to severely active Crohn's disease.
Trial design
The study (NCT03466411) was a Phase 2/Phase 3 trial that enrolled 1409 participants with moderately to severely active Crohn's disease. The trial's purpose was to evaluate the clinical efficacy (GALAXI 1), clinical and endoscopic efficacy (GALAXI 2 and GALAXI 3), and safety of guselkumab. Participants received various dosing regimens of guselkumab, with some groups receiving intravenous (IV) followed by subcutaneous (SC) administration. Comparator arms included placebo and, in some instances, ustekinumab.
Key results
The trial results showed notable findings across several efficacy endpoints. For the outcome of "GALAXI 1: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12":
- Participants in the guselkumab 1200 mg IV q4w followed by 200 mg SC q4w group experienced a mean change of -143.7 Units on a scale (Standard Deviation: 96.58).
- The guselkumab 600 mg IV q4w followed by 200 mg SC q4w group showed a mean change of -139.2 Units on a scale (Standard Deviation: 100.71).
- The guselkumab 200 mg IV q4w followed by 100 mg SC q8w group had a mean change of -159.8 Units on a scale (Standard Deviation: 110.52).
- The placebo q4w followed by placebo q4w group showed a mean change of -34.4 Units on a scale (Standard Deviation: 104.85).
Statistical analyses using a Mixed Model for Repeated Measure indicated significant differences, with Least Square (LS) Mean Differences ranging from 102.7 (95.0% CI: 68.5 to 136.9) to 124.2 (95.0% CI: 89.8 to 158.7), all with a p-value of 0.001.
For the outcome of "Global: GALAXI 2: Percentage of Participants With Both Clinical Response at Week 12 and Clinical Remission at Week 48":
- The guselkumab 200 mg IV q4w followed by 200 mg SC q4w group had 54.8% of participants achieve this endpoint.
- The guselkumab 200 mg IV q4w followed by 100 mg SC q8w group had 49.0% of participants achieve this endpoint.
- The placebo q4w followed by placebo q4w or Ustekinumab 6 mg/kg IV then 90 mg SC q8w group had 11.8% of participants achieve this endpoint.
Further analyses using Mantel Haenszel showed adjusted treatment differences of up to 42.8 (95.0% CI: 31.6 to 53.9), with a p-value of 0.001.
Regarding "Global: GALAXI 2: Percentage of Participants With Both Clinical Response (CR) at Week 12 and Endoscopic Response (ER) at Week 48":
- The guselkumab 200 mg IV q4w followed by 200 mg SC q4w group showed 38.4% of participants achieving this.
- The guselkumab 200 mg IV q4w followed by 100 mg SC q8w group showed 39.2% of participants achieving this.
- The placebo q4w followed by placebo q4w or Ustekinumab 6 mg/kg IV then 90 mg SC q8w group showed 5.3% of participants achieving this.
For "Global: GALAXI 3: Percentage of Participants With Both Clinical Response at Week 12 and Clinical Remission at Week 48":
- The guselkumab 200 mg IV q4w followed by 200 mg SC q4w group had 48.0% of participants achieve this.
- The guselkumab 200 mg IV q4w followed by 100 mg SC q8w group had 46.9% of participants achieve this.
What this means
The posted results from the GALAXI trial indicate that guselkumab demonstrated clinical efficacy in reducing disease activity and achieving clinical remission in patients with moderately to severely active Crohn's disease. The consistent improvement across different dosing regimens and endpoints, including CDAI scores and rates of clinical and endoscopic response and remission, suggests that guselkumab could offer a valuable therapeutic option for this patient population. The significant differences observed compared to placebo highlight its potential benefit.
Source
The information for these trial results was sourced from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03466411, titled "A Study of the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease," were posted on 2025-05-07 on clinicaltrials.gov.