Extension Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Who Previously Participated in a Study With Nusinersen (ONWARD)

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

12 Jul 2021 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Biogen Idec Research Limited

External identifiers

EU CT number

2023-505637-27-00

EudraCT number

2020-004708-32

ClinicalTrials.gov

NCT04729907

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

The primary objective of this study is to evaluate the long-term safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) who previously participated in study 232SM203 (NCT04089566).

Secondary objectives 1

1. The secondary objective of this study is to evaluate the long-term efficacy of nusinersen administered intrathecally at higher doses to participants with SMA who previously participated in study 232SM203 (NCT04089566).

Conditions and MedDRA coding

Spinal Muscular Atrophy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol

Exclusion criteria 2

1. Treatment with another investigational therapy or enrollment in another interventional clinical study
2. Treatment with an approved therapy for SMA after the Day 302 Visit of Study 232SM203 (NCT04089566). Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 13

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1921 ].
2. Change from Baseline in Growth Parameters [ Time Frame: Up to Day 1921 ]..
3. Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Day 1921 ]
4. Number of Participants With Shifts from Baseline in Electrocardiogram (ECG) [ Time Frame: Up to Day 1921 ]
5. Number of Participants With Shifts from Baseline in Vital Signs [ Time Frame: Up to Day 1921 ]
6. Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Up to Day 1921 ]
7. Change from Baseline in Prothrombin Time (PT) [ Time Frame: Up to Day 1921 ]
8. Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Up to Day 1921 ]
9. Change from Baseline in Urine Total Protein [ Time Frame: Up to Day 1921 ]
10. Change from Baseline in Neurological Examination Outcomes for Participants ≤2 Years of Age [ Time Frame: Up to Day 1921].
11. Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age [ Time Frame: Up to Day 1921 ].
12. Percentage of Participants With A Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [ Time Frame: Up to Day 1921 ]
13. Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec [ Time Frame: Up toDay 1921 ]

Secondary endpoints 13

1. Total Number of New World Health Organization (WHO) Motor Milestones [ Time Frame: Up to Day 1921]
2. Number of Participants Who Used Respiratory Support, by Type [ Time Frame: Up to Day 1921 ]
3. Number of Hours Per Day of Respiratory Support [ Time Frame: Up to Day 1921 ]
4. Number of Days That Respiratory Support Is Used [ Time Frame: Up to Day 1921 ]
5. Time to Death (Overall Survival) [ Time Frame: Up to Day 1921 ]
6. Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score [ Time Frame: Up to Day 1921 ].
7. Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones [ Time Frame: Up to Day 1921 ].
8. Percentage of HINE Section 2 Motor Milestone Responders [ Time Frame: Up to Day 1921 ].
9. Percentage of Time Spent on Ventilation [ Time Frame: Up to Day 1921 ].
10. Time to Death or Permanent Ventilation [ Time Frame: Up to Day 1921 ].
11. Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score [ Time Frame: Up to Day 1921 ].
12. Change from Baseline in Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 1921 ]..
13. Change From Baseline in Plasma Levels of Neurofilament (NF) [ Time Frame: Up to Day 1921 ]

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 19

Locations

3 EU/EEA countries · 7 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 56 files

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

Application history

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