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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogen Idec Research Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

14 Sep 2022 → ongoing

Decision date (initial)

2024-06-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Biogen Idec Research Limited

External identifiers

EU CT number

2023-505639-11-00

EudraCT number

2021-001294-23

ClinicalTrials.gov

NCT05067790

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

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 objectives 1

1. The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.

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 survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation
2. Diagnosis of later-onset SMA with symptom onset at age >6 months.
3. Aged ≥15 to ≤50 years at the time of informed consent
4. Body weight >20 kg
5. Received oral risdiplam per the approved label or per the managed access program as follows 1. Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment 2. Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment
6. Able to perform the age-appropriate functional assessments in the study
7. RULM entry item A score ≥3
8. RULM total score ≥5 and ≤30 at Screening
9. Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support
10. Willing to stop risdiplam treatment
11. Willing and able to start treatment with HD nusinersen

Exclusion criteria 9

1. Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration
2. Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period
3. Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter
4. Permanent tracheostomy or permanent ventilation at Screening
5. The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening
6. History of bacterial meningitis, viral encephalitis, or hydrocephalus
7. 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.
8. Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study
9. 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 Inclusion/Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in Total Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 855 ]

Secondary endpoints 2

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1695 ]
2. Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline [ Time Frame: Up to Day 1695 ]

Investigational products

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

Test 2

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

Medical Director

Public contact point

Organisation

Biogen Idec Research Limited

Contact name

Medical Director

Third parties 17

Locations

3 EU/EEA countries · 9 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

Documents 119 files

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

Application history

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