Ozanimod in Induction and Maintenance Therapy for Ulcerative Colitis − True North Study Results

Methodology and Study Progress, Observed Population

This was a randomized double-blind study conducted in 285 centers across 30 countries, including patients aged 18–75 with moderately to severely active ulcerative colitis. The first cohort included 645 patients, and the second cohort included 367. In the maintenance phase, 457 patients were randomized. During the 10-week induction phase, patients in the first cohort received ozanimod hydrochloride at a dose of 1 mg daily (equivalent to 0.92 mg ozanimod) or placebo under double-blind conditions. In the second cohort, all enrolled patients received ozanimod at the same dose under open-label conditions. Patients with a clinical response to ozanimod (defined by a reduction in the Mayo score) proceeded to the maintenance phase, where they were again randomized to receive ozanimod or placebo under double-blind conditions until week 52 of treatment.

Evaluated Parameters

The primary evaluated parameter in both study phases was the proportion of patients achieving clinical remission according to the Mayo score. Remission was defined as a partial rectal bleeding score of 0, a partial stool frequency score of ≤ 1 and a reduction of at least 1 from baseline, and a partial endoscopic score of ≤ 1 (all three subscales range from 0–3 based on increasing severity). Main secondary parameters included in the initial phase were the proportion of patients with a clinical response, improvement in endoscopic findings, and mucosal healing, and in the maintenance phase, the proportion of patients with sustained clinical remission at both week 10 and week 52, remission without the use of corticosteroids for ≥ 12 weeks, and persistent remission (i.e., the proportion of patients in remission at both week 10 and week 52). Safety was also evaluated.

Results

Efficacy

Clinical remission was significantly more frequent in the ozanimod groups compared to placebo. In the initial phase, clinical remission was achieved by 18.4% of patients with ozanimod compared to 6.0% with placebo (p < 0.001). In the maintenance phase, clinical remission (in patients with a response to treatment at week 10) was reported in 37.0% of those receiving ozanimod compared to 18.5% receiving placebo (p < 0.001).

The incidence of clinical response to treatment was also significantly higher in the ozanimod groups: 47.8% vs. 25.9% (p < 0.001) in the initial phase and 60.0% vs. 41.0% (p < 0.001) in the maintenance phase.

In both study phases, treatment with ozanimod resulted in significantly better outcomes compared to placebo across all secondary evaluated parameters.

Safety

The incidence of infections of any severity was comparable between ozanimod and placebo in the initial phase, while in the maintenance phase it was higher in patients receiving ozanimod. Serious infections occurred in all therapeutic groups in < 2% of patients over the 52-week study period. Increased aminotransferase levels were more common with ozanimod treatment.

Conclusion

The phase III True North study showed significantly higher efficacy of ozanimod compared to placebo in both the induction and maintenance treatment of ulcerative colitis in adult patients.

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Source: Sandborn W. J., Feagan B. G., D'Haens G. et al.; True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2021; 385 (14): 1280−1291, doi: 10.1056/NEJMoa2033617. 

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