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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogen Idec Research Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

2 Sep 2021 → 9 Oct 2025

Decision date (initial)

2024-07-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Biogen Idec Research Limited

External identifiers

EU CT number

2023-505640-18-00

EudraCT number

2020-003492-18

ClinicalTrials.gov

NCT04488133

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Pharmacogenetic, Safety, Pharmacodynamic

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 objectives 1

1. 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.

Conditions and MedDRA coding

Spinal Muscular Atrophy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Genetic documentation of 5q SMA homozygous gene survival motor neuron 1 (SMN1) deletion or mutation, or compound heterozygous mutation
2. SMN2 copy number of ≥1
3. ≤36 months of age at the time of first Nusinersen dose
4. Must have previously received onasemnogene abeparvovec per the approved label or local/regional regulations ≥2 months prior to first Nusinersen dose
5. Must have suboptimal clinical status per the Investigator
6. Additional Criterion for Subgroups A and B: <300 days of age at the time of first Nusinersen dose
7. Additional Criterion for Subgroups A and B: SMN2 copy number of 2
8. Additional Criterion for Subgroup A: SMA symptom onset ≤4 months (120 days) of age
9. Additional Criterion for Subgroup A: Must have received intravenous (IV) onasemnogene abeparvovec at >6 weeks to ≤6 months (43 days to 180 days) of age
10. Additional Criterion for Subgroup A: Must have received IV onasemnogene abeparvovec after SMA symptom onset
11. Additional Criterion for Subgroup B: Must have received IV onasemnogene abeparvovec at ≤6 weeks (42 days) of age

Exclusion criteria 4

1. Prior exposure to Nusinersen
2. Ongoing severe or serious AEs related to onasemnogene abeparvovec
3. 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
4. Additional Criterion 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Total Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones Score [ Time Frame: Up to Day 778 ]

Secondary endpoints 11

1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 778 ]
2. Number of Participants with Change from Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Day 778 ]
3. Number of Participants with Change from Baseline in Electrocardiograms (ECGs) [ Time Frame: Up to Day 778 ]
4. Number of Participants with Change from Baseline in Vital Signs [ Time Frame: Up to Day 778 ]
5. Number of Participants who Achieved Motor Milestones as Assessed by World Health Organization (WHO) Criteria [ Time Frame: Up to Day 778 ]
6. Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Score [ Time Frame: Up to Day 778 ]
7. Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score [ Time Frame: Up to Day 778 ]
8. Change from Baseline in Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 778 ]
9. Time to Death or Permanent Ventilation [ Time Frame: Up to Day 778 ]
10. Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Neurofilament Light Subunit (NF-L) [ Time Frame: Up to Day 659 ]
11. Change From Baseline in Plasma Levels of NF-L [ Time Frame: Up to Day 778 ]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biogen Idec Research Limited

Sponsor organisation

Biogen Idec Research Limited

Address

Building 5 Foundation Park, Roxborough Way Roxborough Way

City

Maidenhead

Postcode

SL6 3UD

Country

United Kingdom

Scientific contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Third parties 15

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications