A Study of Nusinersen Among Participants With Spinal Muscular Atrophy Who Received Onasemnogene Abeparvovec

Phase 1

• Conditions: Muscular Atrophy, Spinal; MedDRA version: 20.1Level: PTClassification code 10041582Term: Spinal muscular atrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2020-003492-18-DE
• Lead Sponsor: Biogen Idec Research Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-18
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Key Inclusion Criteria:
- Genetic documentation of 5q SMA homozygous gene survival motor
neuron 1 (SMN1) deletion or mutation, or compound heterozygous
mutation
- SMN2 copy number of = 1
- = 36 months of age at the time of first nusinersen dose
- Must have previously received onasemnogene abeparvovec per the
approved label or local/regional regulations = 2 months prior to first
nusinersen dose
- Must have suboptimal clinical status per the Investigator
For Subgroups A and B:
- < 300 days of age at the time of first nusinersen dose
- SMN2 copy number of 2
For Subgroup A:
- SMA symptom onset = 4 months (120 days) of age
- Must have received intravenous (IV) onasemnogene abeparvovec at >6
weeks to = 6 months (43 days to 180 days) of age
- Must have received IV onasemnogene abeparvovec after SMA symptom
onset
For Subgroup B:
- Must have received IV onasemnogene abeparvovec at = 6 weeks (42
days) of age

Note: other protocol defined Inclusion/Exclusion criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range: 49
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Key Exclusion Criteria:
- Prior exposure to nusinersen
- Ongoing severe or serious AEs related to onasemnogene abeparvovec
- Treatment with an investigational drug, biological agent, or device
within 30 days or 5 half-lives of the agent, whichever is longer, prior to
study; any prior or current treatment with any survival motor neuron 2
(SMN2)-directed splicing modifier; prior antisense oligonucleotide
treatment or cell transplantation; gene therapy for the treatment of SMA
other than onasemnogene abeparvovec. Note: treatment with
onasemnogene abeparvovec as part of an investigational study is
allowed
For Subgroups A and B:
- Weight-for-age is below the third percentile, based on WHO Child
Growth Standards at the time of receiving onasemnogene abeparvovec.
Adjustments for the gestational weight of premature babies enrolled in
Subgroups A and B are allowed provided IV onasemnogene abeparvovec
was dosed per the approved label or per local/regional regulations.

Note: other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the clinical outcomes following treatment with nusinersen in participants with spinal muscular atrophy (SMA) who previously received onasemnogene abeparvovec.;Secondary Objective: The secondary objectives of this study are to evaluate the safety and tolerability; clinical outcomes and pharmacodynamics (PD) of nusinersen treatment in participants with SMA who previously received onasemnogene abeparvovec.;Primary end point(s): Total Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones Score<br>;Timepoint(s) of evaluation of this end point: Up to Day 778