A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants with Spinal Muscular Atrophy Previously Treated with Risdiplam

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: EUCTR2021-001294-23-BE
• Lead Sponsor: Biogen Idec Research Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-12-16
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

Key Inclusion Criteria:
- Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
- Diagnosis of later-onset SMA with symptom onset at age >6 months.
- Aged =5 to =39 years at the time of informed consent for nusinersen-naïve participants.
- Aged =18 to =39 years at time of informed consent for nusinersen-experienced participants.
- Body weight >20 kg.
- Received oral risdiplam per the approved label or per the managed access program as follows
Nusinersen-naive participants must have had prior treatment with risdiplam for =6 months and =12 months before enrollment.
Nusinersen-experienced participants must have stopped nusinersen for =16 months and have been on risdiplam for =12 months and =18 months before enrollment.
- Able to perform the age-appropriate functional assessments in the study.
- RULM entry item A score =3.
- RULM total score =5 and =30 at Screening.
- Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
- Willing to stop risdiplam treatment.
- Willing and able to start treatment with nusinersen.

NOTE: Other protocol defined Inclusion criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range: 135
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Key Exclusion Criteria:
- Any major illness within 1 month before the Screening examination or within 1 week prior to Screening and up to first dose administration.
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
- Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
- History of bacterial meningitis, viral encephalitis, or hydrocephalus.
- Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
- Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study. - Treatment with an investigational drug, biological agent, or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.

NOTE: Other protocol defined 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 motor function following treatment with HD nusinersen in participants with spinal muscular atrophy (SMA) previously treated with risdiplam.;Secondary Objective: The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.;Primary end point(s): Change in Total Revised Upper Limb Module (RULM) Score;Timepoint(s) of evaluation of this end point: Up to Day 855

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)<br>2) Number of Participants With Change from Baseline in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry;Timepoint(s) of evaluation of this end point: 1) Up to Day 855<br>2) Up to Day 855