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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04729907




Registration number
NCT04729907
Ethics application status
Date submitted
11/12/2020
Date registered
29/01/2021
Date last updated
26/10/2023

Titles & IDs
Public title
Extension Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Who Previously Participated in a Study With Nusinersen
Scientific title
A Long-Term Extension Study of Nusinersen (BIIB058) Administered at Higher Doses in Participants With Spinal Muscular Atrophy Who Previously Participated in an Investigational Study With Nusinersen
Secondary ID [1] 0 0
2020-004708-32
Secondary ID [2] 0 0
232SM302
Universal Trial Number (UTN)
Trial acronym
ONWARD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Muscular Atrophy, Spinal 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Nusinersen

Experimental: BIIB058 28 mg (Prior Maintenance Dose 28 mg) - Participants who received maintenance dose of 28 milligram (mg) nusinersen in study 232SM203 (NCT04089566), will receive maintenance dose of 28 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 961.

Experimental: BIIB058 50/28 mg (Prior Maintenance Dose 12 mg) - Participants who received maintenance dose of 12 mg nusinersen in study 232SM203 (NCT04089566), will receive loading dose of 50 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 961.


Treatment: Drugs: Nusinersen
Administered as specified in the treatment arm
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to Day 1081
Primary outcome [2] 0 0
Change from Baseline in Growth Parameters
Timepoint [2] 0 0
Up to Day 1081
Primary outcome [3] 0 0
Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
Timepoint [3] 0 0
Up to Day 1081
Primary outcome [4] 0 0
Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
Timepoint [4] 0 0
Up to Day 1081
Primary outcome [5] 0 0
Number of Participants With Shifts from Baseline in Vital Signs
Timepoint [5] 0 0
Up to Day 1081
Primary outcome [6] 0 0
Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
Timepoint [6] 0 0
Up to Day 961
Primary outcome [7] 0 0
Change from Baseline in Prothrombin Time (PT)
Timepoint [7] 0 0
Up to Day 961
Primary outcome [8] 0 0
Change from Baseline in International Normalized Ratio (INR)
Timepoint [8] 0 0
Up to Day 961
Primary outcome [9] 0 0
Change from Baseline in Urine Total Protein
Timepoint [9] 0 0
Up to Day 1081
Primary outcome [10] 0 0
Change from Baseline in Neurological Examination Outcomes for Participants =2 Years of Age
Timepoint [10] 0 0
Up to Day 1081
Primary outcome [11] 0 0
Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age
Timepoint [11] 0 0
Up to Day 1081
Primary outcome [12] 0 0
Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
Timepoint [12] 0 0
Up to Day 1081
Primary outcome [13] 0 0
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
Timepoint [13] 0 0
Up to Day 1081
Secondary outcome [1] 0 0
Total Number of New World Health Organization (WHO) Motor Milestones
Timepoint [1] 0 0
Up to Day 1081
Secondary outcome [2] 0 0
Number of Participants Who Used Respiratory Support, by Type
Timepoint [2] 0 0
Up to Day 1081
Secondary outcome [3] 0 0
Number of Hours Per Day of Respiratory Support
Timepoint [3] 0 0
Up to Day 1081
Secondary outcome [4] 0 0
Number of Days That Respiratory Support Is Used
Timepoint [4] 0 0
Up to Day 1081
Secondary outcome [5] 0 0
Time to Death (Overall Survival)
Timepoint [5] 0 0
Up to Day 1081
Secondary outcome [6] 0 0
Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score
Timepoint [6] 0 0
Up to Day 1081
Secondary outcome [7] 0 0
Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones
Timepoint [7] 0 0
Up to Day 1081
Secondary outcome [8] 0 0
Percentage of HINE Section 2 Motor Milestone Responders
Timepoint [8] 0 0
Up to Day 1081
Secondary outcome [9] 0 0
Percentage of Time Spent on Ventilation
Timepoint [9] 0 0
Up to Day 1081
Secondary outcome [10] 0 0
Time to Death or Permanent Ventilation
Timepoint [10] 0 0
Up to Day 1081
Secondary outcome [11] 0 0
Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
Timepoint [11] 0 0
Up to Day 1081
Secondary outcome [12] 0 0
Change from Baseline in Revised Upper Limb Module (RULM) Score
Timepoint [12] 0 0
Up to Day 1081

Eligibility
Key inclusion criteria
Key

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

Key
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Treatment with another investigational therapy or enrollment in another interventional
clinical study

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2026
Actual
Sample size
Target
172
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Brazil
State/province [8] 0 0
Porto Alegre
Country [9] 0 0
Brazil
State/province [9] 0 0
São Paulo
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Chile
State/province [11] 0 0
Santiago
Country [12] 0 0
China
State/province [12] 0 0
Guangdong
Country [13] 0 0
Colombia
State/province [13] 0 0
Bogota
Country [14] 0 0
Estonia
State/province [14] 0 0
Tallinn
Country [15] 0 0
Germany
State/province [15] 0 0
Baden Wuerttemberg
Country [16] 0 0
Germany
State/province [16] 0 0
Hessen
Country [17] 0 0
Italy
State/province [17] 0 0
Milano
Country [18] 0 0
Italy
State/province [18] 0 0
Roma
Country [19] 0 0
Japan
State/province [19] 0 0
Fukuoka-Ken
Country [20] 0 0
Japan
State/province [20] 0 0
Hyogo-Ken
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo-To
Country [22] 0 0
Lebanon
State/province [22] 0 0
Beirut
Country [23] 0 0
Mexico
State/province [23] 0 0
Distrito Federal
Country [24] 0 0
Mexico
State/province [24] 0 0
Guadalajara
Country [25] 0 0
Poland
State/province [25] 0 0
Warszawa
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Ekaterinburg
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Moskva
Country [28] 0 0
Saudi Arabia
State/province [28] 0 0
Dammam
Country [29] 0 0
Saudi Arabia
State/province [29] 0 0
Jeddah
Country [30] 0 0
Saudi Arabia
State/province [30] 0 0
Riyadh
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Valencia
Country [33] 0 0
Taiwan
State/province [33] 0 0
Kaohsiung
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).

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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04729907
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04729907