A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
Summary
The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset with infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.
Timeline
- Start
- 2014-08-19
- Primary completion
- 2016-11-21
- Completion
- 2016-11-21
Outcome
Met primary endpoint
Stopped (Enrollment): “After a positive interim analysis, the decision was made to terminate the study early to allow for participants to enroll into an open label study”
registry NUMBER Control: 0 percentage of participants NUMBER Nusinersen: 51 percentage of participants NCT02193074 ↗
registry analysis (unspecified test); Control vs Nusinersen; p < 0.0001; Difference in percentages 50.68 (95% CI 31.81 to 66.48); Fisher Exact NCT02193074 ↗
registry analysis (unspecified test); Control vs Nusinersen; p = 0.0164; Hazard Ratio (HR) 0.530 (95% CI 0.3156 to 0.8902); Cox proportional hazards model NCT02193074 ↗
paper the likelihood of event-free survival was higher in the nusinersen group than in the control group PMID 29091570 ↗
release “met the primary endpoint pre-specified for the interim analysis of ENDEAR, the Phase 3 trial evaluating nusinersen in infantile-onset (consistent with Type 1) SMA.” biogen.com ↗
release “The ENDEAR interim analysis demonstrated that infants receiving nusinersen experienced a statistically significant improvement in the achievement of motor milestones” biogen.com ↗
Publications
- Kokaliaris C, Evans R, Hawkins N, Mahajan A, Scott DA, Sutherland CS, Nam J, Sajeev G. Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy. Adv Ther. 2024 Jun;41(6):2414-2434. doi: 10.1007/s12325-024-02845-6. Epub 2024 May 5.
- Darras BT, Farrar MA, Mercuri E, Finkel RS, Foster R, Hughes SG, Bhan I, Farwell W, Gheuens S. An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials. CNS Drugs. 2019 Sep;33(9):919-932. doi: 10.1007/s40263-019-00656-w.
- Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guerin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM. Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1. Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.
- Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.
- Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, Yamashita M, Rigo F, Hung G, Schneider E, Norris DA, Xia S, Bennett CF, Bishop KM. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017-3026. doi: 10.1016/S0140-6736(16)31408-8. Epub 2016 Dec 7.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Nusinersen | Antisense oligonucleotide | — | Intrathecal |