Multiple sclerosis and related disorders · 2025
Ponesimod as add-on treatment in patients with active relapsing multiple sclerosis under dimethyl fumarate (POINT): A phase 3, randomized, placebo-controlled clinical trial.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
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Kappos Ludwig, Burcklen Michel, D'Ambrosio Daniele, Fox Robert J, Freedman Mark S, Havrdova Eva Kubala, Hennessy Brian, Hohlfeld Reinhard, Larbalestier Anna, Lemle Alexandre, Lindenstrøm Ewa, Lublin Fred, Montalban Xavier, Sidorenko Tatiana, Sprenger Till, Vaclavkova Andrea, Wuerfel Jens, Pozzilli Carlo
Аннотация
BACKGROUND: Combining two oral therapies with different mechanisms could be an attractive treatment strategy for multiple sclerosis (MS) to increase efficacy; however, evidence of such efficacy and safety is lacking.
OBJECTIVES: The phase 3 randomized, double-blind, placebo-controlled POINT study evaluated efficacy and safety of ponesimod 20 mg versus placebo as an add-on therapy to ongoing dimethyl fumarate (DMF) treatment in patients with active relapsing MS despite DMF monotherapy.
METHODS: Patients (18-55 years) were randomized (1:1) to ponesimod+DMF or placebo+DMF orally once-daily for ≤156 weeks. Primary endpoint was annualized relapse rate (ARR) at end-of-study (EOS). Secondary endpoints were 12-week confirmed disability accumulation (CDA), time-to-first confirmed relapse, and number of combined unique active lesions (CUALs) on brain Magnetic resonance imaging (MRI) at EOS.
RESULTS: The study was prematurely terminated due to slow recruitment; of 600 planned patients, 136 (23 %; [ponesimod: n = 68, placebo: n = 68]) were randomized. Primary endpoint (ARR) was not met (rate ratio, ponesimod+DMF versus placebo+DMF: 1.2; p = 0.5252). Ponesimod+DMF group showed a lower mean number of CUALs/year (rate ratio: 0.37; p = 0.0072). Other efficacy outcomes did not differ between the treatment groups. Adverse events (AEs) were comparable between groups (ponesimod+DMF: 48 [71.6 %]; placebo+DMF: 53 [77.9 %]); dizziness was the most commonly reported AE in the ponesimod+DMF group (10.4 %).
CONCLUSIONS: This terminated study did not demonstrate the superiority of ponesimod+DMF on clinical efficacy endpoints. In the exploratory analysis ponesimod+DMF versus DMF alone appeared associated with a lower disease activity as assessed by MRI. No new safety signals were reported for ponesimod+DMF.
GOV IDENTIFIER: NCT02907177 URL: https://clinicaltrials.gov/study/NCT02907177.
OBJECTIVES: The phase 3 randomized, double-blind, placebo-controlled POINT study evaluated efficacy and safety of ponesimod 20 mg versus placebo as an add-on therapy to ongoing dimethyl fumarate (DMF) treatment in patients with active relapsing MS despite DMF monotherapy.
METHODS: Patients (18-55 years) were randomized (1:1) to ponesimod+DMF or placebo+DMF orally once-daily for ≤156 weeks. Primary endpoint was annualized relapse rate (ARR) at end-of-study (EOS). Secondary endpoints were 12-week confirmed disability accumulation (CDA), time-to-first confirmed relapse, and number of combined unique active lesions (CUALs) on brain Magnetic resonance imaging (MRI) at EOS.
RESULTS: The study was prematurely terminated due to slow recruitment; of 600 planned patients, 136 (23 %; [ponesimod: n = 68, placebo: n = 68]) were randomized. Primary endpoint (ARR) was not met (rate ratio, ponesimod+DMF versus placebo+DMF: 1.2; p = 0.5252). Ponesimod+DMF group showed a lower mean number of CUALs/year (rate ratio: 0.37; p = 0.0072). Other efficacy outcomes did not differ between the treatment groups. Adverse events (AEs) were comparable between groups (ponesimod+DMF: 48 [71.6 %]; placebo+DMF: 53 [77.9 %]); dizziness was the most commonly reported AE in the ponesimod+DMF group (10.4 %).
CONCLUSIONS: This terminated study did not demonstrate the superiority of ponesimod+DMF on clinical efficacy endpoints. In the exploratory analysis ponesimod+DMF versus DMF alone appeared associated with a lower disease activity as assessed by MRI. No new safety signals were reported for ponesimod+DMF.
GOV IDENTIFIER: NCT02907177 URL: https://clinicaltrials.gov/study/NCT02907177.