Nusinersen in children with SMA who received onasemnogene abeparvovec: design of the phase 4, open-label RESPOND study


Clinical Trials

Poster Number: 66


Julie Parsons MD, John Brandsema MD, Richard Finkel MD, Crystal Proud MD, Kathryn J. Swoboda MD, Richard Foster , Corinne Makepeace , Angela D. Paradis ScD, Russell Chin , Zdenek Berger PhD, Wildon Farwell MD, on behalf of the RESPOND Study Group


1. Children Hospital-Colorado, 2. Children's Hospital of Philadelphia, 3. Translational Neuroscience Program, St. Jude Children's Research Hospital, Memphis, TN, US, 4. Children's Hospital of The King's Daughters, Norfolk, VA, USA, 5. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA, 6. Biogen, Maidenhead, UK, 7. Biogen, Maidenhead, UK, 8. Biogen, Cambridge, MA, USA, 9. Biogen, Cambridge, MA, USA, 10. Biogen, Cambridge, MA, USA, 11. Biogen, Cambridge, MA, USA

Background: Nusinersen is an antisense oligonucleotide that has shown significant and clinically meaningful efficacy on motor function and survival endpoints across a broad spectrum of spinal muscular atrophy (SMA) phenotypes. Onasemnogene abeparvovec is an adeno-associated viral vector gene therapy for the treatment of SMA. There have been reports of some patients with SMA receiving nusinersen after treatment with onasemnogene abeparvovec; however, there has been no systematic evaluation of clinical outcomes or safety of treatment with nusinersen following onasemnogene abeparvovec.
Objectives: Describe the study design of the RESPOND (NCT04488133) clinical trial to evaluate nusinersen in participants who previously received onasemnogene abeparvovec.
Methods: RESPOND is a phase 4, open-label, multicenter, single-arm study to assess the clinical outcomes, safety, and tolerability of multiple doses of nusinersen administered by intrathecal (IT) injection to participants who previously received intravenous onasemnogene abeparvovec.
Approximately 60 participants who have suboptimal clinical status after onasemnogene abeparvovec administration as determined by the investigator, will be enrolled across 20 sites globally. Eligible participants are those aged ≤36 months at first nusinersen dose, have ≥1 SMN2 copy, and have received onasemnogene abeparvovec (≥3 months before the first nusinersen dose). Participants must not have previously received nusinersen.
Forty participants will be recruited into Subgroup A with the following criteria: ≤9 months of age at first nusinersen dose, 2 SMN2 copies, SMA symptom onset ≤4 months of age and before receiving onasemnogene abeparvovec. The overall duration is ~2 years consisting of 3-week screening, 95-week treatment, and 17-week follow-up periods. During the treatment period, participants will receive the approved regimen of 12 mg nusinersen administered IT by lumbar puncture on Days 1, 15, 29, and 64 (loading period), followed by maintenance doses of 12 mg nusinersen IT every 4 months.
The primary endpoint is the total Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone score. Secondary endpoints include safety, tolerability, WHO motor milestones, motor function assessments, and event-free survival.
Results: Enrollment is planned to begin in Q1 2021.
Study Support: Biogen