Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
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
Query!
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
Query!
Secondary ID [1]
0
0
2020-004708-32
Query!
Secondary ID [2]
0
0
232SM302
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
ONWARD
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Muscular Atrophy, Spinal
0
0
Query!
Condition category
Condition code
Musculoskeletal
0
0
0
0
Query!
Other muscular and skeletal disorders
Query!
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Other
0
0
0
0
Query!
Research that is not of generic health relevance and not applicable to specific health categories listed above
Query!
Intervention/exposure
Study type
Interventional(has expanded access)
Query!
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
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Query!
Assessment method [1]
0
0
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect, or is a medically important event.
Query!
Timepoint [1]
0
0
Up to Day 1081
Query!
Primary outcome [2]
0
0
Change from Baseline in Growth Parameters
Query!
Assessment method [2]
0
0
Growth parameters will be assessed by measuring body length or height (if feasible and appropriate), ulnar length (all participants), and head circumference, chest circumference, and arm circumference (all participants 3 years of age and younger) in centimeters.
Query!
Timepoint [2]
0
0
Up to Day 1081
Query!
Primary outcome [3]
0
0
Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
Up to Day 1081
Query!
Primary outcome [4]
0
0
Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
Up to Day 1081
Query!
Primary outcome [5]
0
0
Number of Participants With Shifts from Baseline in Vital Signs
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
Up to Day 1081
Query!
Primary outcome [6]
0
0
Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
Up to Day 961
Query!
Primary outcome [7]
0
0
Change from Baseline in Prothrombin Time (PT)
Query!
Assessment method [7]
0
0
Query!
Timepoint [7]
0
0
Up to Day 961
Query!
Primary outcome [8]
0
0
Change from Baseline in International Normalized Ratio (INR)
Query!
Assessment method [8]
0
0
Query!
Timepoint [8]
0
0
Up to Day 961
Query!
Primary outcome [9]
0
0
Change from Baseline in Urine Total Protein
Query!
Assessment method [9]
0
0
Query!
Timepoint [9]
0
0
Up to Day 1081
Query!
Primary outcome [10]
0
0
Change from Baseline in Neurological Examination Outcomes for Participants =2 Years of Age
Query!
Assessment method [10]
0
0
For participants 2 years of age and younger, the Hammersmith Infant Neurological Exam (HINE) Sections 1 and 3 will be conducted. This standard examination (developed by [Dubowitz and Dubowitz 1981]) is a quantitative scorable method for assessing the neurological development of infants between 2 and 24 months of age. The examination includes assessment of cranial nerve functions, posture, movements, tone, and reflexes. The HINE Section 1 form utilized in ONWARD contains 26 items and the Section 3 form utilized contains 3 items. For HINE Section 1 items, each item is scored 0-3. For HINE Section 3 items, scoring is variable (1-4, 1-5, or 1-6). Higher scores indicate better neurological function.
Query!
Timepoint [10]
0
0
Up to Day 1081
Query!
Primary outcome [11]
0
0
Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age
Query!
Assessment method [11]
0
0
For all participants >2 years of age, standard neurological examinations, which include assessments of mental status, level of consciousness, sensory function, motor function, cranial nerve function, and reflexes, will be conducted.
Query!
Timepoint [11]
0
0
Up to Day 1081
Query!
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
Query!
Assessment method [12]
0
0
Query!
Timepoint [12]
0
0
Up to Day 1081
Query!
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
Query!
Assessment method [13]
0
0
Query!
Timepoint [13]
0
0
Up to Day 1081
Query!
Secondary outcome [1]
0
0
Total Number of New World Health Organization (WHO) Motor Milestones
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Up to Day 1081
Query!
Secondary outcome [2]
0
0
Number of Participants Who Used Respiratory Support, by Type
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
Up to Day 1081
Query!
Secondary outcome [3]
0
0
Number of Hours Per Day of Respiratory Support
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
Up to Day 1081
Query!
Secondary outcome [4]
0
0
Number of Days That Respiratory Support Is Used
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
Up to Day 1081
Query!
Secondary outcome [5]
0
0
Time to Death (Overall Survival)
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
Up to Day 1081
Query!
Secondary outcome [6]
0
0
Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score
Query!
Assessment method [6]
0
0
The CHOP INTEND test is designed to evaluate the motor skills of infants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4. The total score ranges from 0-64, with higher scores depicting better response. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
Query!
Timepoint [6]
0
0
Up to Day 1081
Query!
Secondary outcome [7]
0
0
Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones
Query!
Assessment method [7]
0
0
Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is the sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
Query!
Timepoint [7]
0
0
Up to Day 1081
Query!
Secondary outcome [8]
0
0
Percentage of HINE Section 2 Motor Milestone Responders
Query!
Assessment method [8]
0
0
Section 2 of HINE is used to assess motor milestones of participants. It is composed of 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. HINE section 2 motor milestone responder is participant who demonstrates at least 2-point increase in category of ability to kick or increase to maximal score on that category or 1-point increase in motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and among 7 motor milestone categories (excluding voluntary grasp), participant demonstrates improvement in more categories than worsening. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
Query!
Timepoint [8]
0
0
Up to Day 1081
Query!
Secondary outcome [9]
0
0
Percentage of Time Spent on Ventilation
Query!
Assessment method [9]
0
0
This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
Query!
Timepoint [9]
0
0
Up to Day 1081
Query!
Secondary outcome [10]
0
0
Time to Death or Permanent Ventilation
Query!
Assessment method [10]
0
0
Permanent ventilation is defined as tracheostomy or =16 hours of ventilation/day continuously for >21 days in the absence of an acute reversible event. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
Query!
Timepoint [10]
0
0
Up to Day 1081
Query!
Secondary outcome [11]
0
0
Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
Query!
Assessment method [11]
0
0
The HFMSE is a tool used to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale (HFMS) was expanded to include 13 additional items to improve sensitivity for the higher functioning ambulant population. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all activities, with a maximum score of 66 with higher scores depicting better ability to perform activities. Participants = 2 years of age (at the time of the study visit) will be evaluated with HFMSE.
Query!
Timepoint [11]
0
0
Up to Day 1081
Query!
Secondary outcome [12]
0
0
Change from Baseline in Revised Upper Limb Module (RULM) Score
Query!
Assessment method [12]
0
0
The RULM is developed to assess upper limb functional abilities participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function. Participants = 2 years of age (at the time of the study visit) will be evaluated with RULM.
Query!
Timepoint [12]
0
0
Up to Day 1081
Query!
Eligibility
Key inclusion criteria
Key
- Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the
study protocol
Key
Query!
Minimum age
No limit
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
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
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
19/04/2021
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
31/07/2026
Query!
Actual
Query!
Sample size
Target
172
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Colorado
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Illinois
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Maryland
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Massachusetts
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Tennessee
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Texas
Query!
Country [8]
0
0
Brazil
Query!
State/province [8]
0
0
Porto Alegre
Query!
Country [9]
0
0
Brazil
Query!
State/province [9]
0
0
São Paulo
Query!
Country [10]
0
0
Canada
Query!
State/province [10]
0
0
Ontario
Query!
Country [11]
0
0
Chile
Query!
State/province [11]
0
0
Santiago
Query!
Country [12]
0
0
China
Query!
State/province [12]
0
0
Guangdong
Query!
Country [13]
0
0
Colombia
Query!
State/province [13]
0
0
Bogota
Query!
Country [14]
0
0
Estonia
Query!
State/province [14]
0
0
Tallinn
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Baden Wuerttemberg
Query!
Country [16]
0
0
Germany
Query!
State/province [16]
0
0
Hessen
Query!
Country [17]
0
0
Italy
Query!
State/province [17]
0
0
Milano
Query!
Country [18]
0
0
Italy
Query!
State/province [18]
0
0
Roma
Query!
Country [19]
0
0
Japan
Query!
State/province [19]
0
0
Fukuoka-Ken
Query!
Country [20]
0
0
Japan
Query!
State/province [20]
0
0
Hyogo-Ken
Query!
Country [21]
0
0
Japan
Query!
State/province [21]
0
0
Tokyo-To
Query!
Country [22]
0
0
Lebanon
Query!
State/province [22]
0
0
Beirut
Query!
Country [23]
0
0
Mexico
Query!
State/province [23]
0
0
Distrito Federal
Query!
Country [24]
0
0
Mexico
Query!
State/province [24]
0
0
Guadalajara
Query!
Country [25]
0
0
Poland
Query!
State/province [25]
0
0
Warszawa
Query!
Country [26]
0
0
Russian Federation
Query!
State/province [26]
0
0
Ekaterinburg
Query!
Country [27]
0
0
Russian Federation
Query!
State/province [27]
0
0
Moskva
Query!
Country [28]
0
0
Saudi Arabia
Query!
State/province [28]
0
0
Dammam
Query!
Country [29]
0
0
Saudi Arabia
Query!
State/province [29]
0
0
Jeddah
Query!
Country [30]
0
0
Saudi Arabia
Query!
State/province [30]
0
0
Riyadh
Query!
Country [31]
0
0
Spain
Query!
State/province [31]
0
0
Madrid
Query!
Country [32]
0
0
Spain
Query!
State/province [32]
0
0
Valencia
Query!
Country [33]
0
0
Taiwan
Query!
State/province [33]
0
0
Kaohsiung
Query!
Country [34]
0
0
Taiwan
Query!
State/province [34]
0
0
Taipei
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Biogen
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
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).
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04729907
Query!
Trial related presentations / publications
Query!
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
Query!
Contacts
Principal investigator
Name
0
0
Medical Director
Query!
Address
0
0
Biogen
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04729907
Download to PDF