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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04089566




Registration number
NCT04089566
Ethics application status
Date submitted
11/09/2019
Date registered
13/09/2019
Date last updated
14/10/2021

Titles & IDs
Public title
Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
Scientific title
Escalating Dose and Randomized, Controlled Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
Secondary ID [1] 0 0
2019-002663-10
Secondary ID [2] 0 0
232SM203
Universal Trial Number (UTN)
Trial acronym
DEVOTE
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
Description of intervention(s) / exposure
Treatment: Drugs - Nusinersen

Experimental: 28/28 Milligram (mg) Safety Group - Part A: Participants with later-onset SMA will receive loading doses of 28 mg of nusinersen intrathecally on Days 1, 15 and 29 followed by maintenance doses of 28 mg on Days 149 and 269.

Active Comparator: 12/12 mg Randomized Control Group - Part B: Participants with infantile- or later-onset SMA will receive loading doses of 12 mg of nusinersen intrathecally on Days 1, 15, 29, and 64 followed by maintenance doses of 12 mg on Days 183 and 279. Sham procedure will be administered on Day 135.

Experimental: 50/28 mg Randomized Treatment Group - Part B: Participants with infantile- or later-onset SMA will receive loading doses of 50 mg of nusinersen intrathecally on Days 1 and 15 followed by maintenance doses of 28 mg on Days 135 and 279. Sham procedure will be administered on Days 29, 64 and 183.

Experimental: 12/50/28 mg Titration Group - Part C: Participants who have been receiving the approved dose of 12 mg for at least 1 year prior to entry, will receive a single bolus dose of 50 mg of nusinersen intrathecally on Day 1 (4 months after their most recent maintenance dose of 12 mg) followed by maintenance doses of 28 mg on Days 121 and 241.


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
Part B Infantile-onset SMA: Change from Baseline in CHOP INTEND Total Score - 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.
Timepoint [1] 0 0
Baseline up to Day 183
Primary outcome [2] 0 0
Part A and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - 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 (including an abnormal assessment such as an abnormal laboratory value), 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.
Timepoint [2] 0 0
Screening up to Day 389
Primary outcome [3] 0 0
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters
Timepoint [3] 0 0
Screening up to Day 302
Primary outcome [4] 0 0
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs)
Timepoint [4] 0 0
Screening up to Day 302
Primary outcome [5] 0 0
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs
Timepoint [5] 0 0
Screening up to Day 302
Primary outcome [6] 0 0
Part A and C: Change from Baseline in Body Length/Height
Timepoint [6] 0 0
Baseline up to Day 302
Primary outcome [7] 0 0
Part C Infantile-onset SMA: Change from Baseline in Head Circumference
Timepoint [7] 0 0
Baseline up to Day 302
Primary outcome [8] 0 0
Part C Infantile-onset SMA: Change from Baseline in Chest Circumference
Timepoint [8] 0 0
Baseline up to Day 302
Primary outcome [9] 0 0
Part C Infantile-onset SMA: Change from Baseline in Arm Circumference
Timepoint [9] 0 0
Baseline up to Day 302
Primary outcome [10] 0 0
Part A and C Later-onset SMA: Change from Baseline in Ulnar Length
Timepoint [10] 0 0
Baseline up to Day 302
Primary outcome [11] 0 0
Part A and C: Ratio of Weight for Age
Timepoint [11] 0 0
Baseline up to Day 302
Primary outcome [12] 0 0
Part A and C: Ratio of Weight for Length
Timepoint [12] 0 0
Baseline up to Day 302
Primary outcome [13] 0 0
Part C: Ratio of Head-to-chest Circumference
Timepoint [13] 0 0
Baseline up to Day 302
Primary outcome [14] 0 0
Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
Timepoint [14] 0 0
Baseline up to Day 269
Primary outcome [15] 0 0
Part A and C: Change from Baseline in Prothrombin Time (PT)
Timepoint [15] 0 0
Baseline up to Day 269
Primary outcome [16] 0 0
Part A and C: Change from Baseline in International Normalized Ratio (INR)
Timepoint [16] 0 0
Baseline up to Day 269
Primary outcome [17] 0 0
Part A and C: Change in Urine Total Protein
Timepoint [17] 0 0
Baseline up to Day 302
Primary outcome [18] 0 0
Part A and C: Change from Baseline in Neurological Examination Outcomes
Timepoint [18] 0 0
Baseline up to Day 302
Primary outcome [19] 0 0
Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
Timepoint [19] 0 0
Baseline up to Day 302
Primary outcome [20] 0 0
Part A and C: 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 [20] 0 0
Baseline up to Day 302
Secondary outcome [1] 0 0
Part B Infantile-onset SMA: Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders - Section 2 of the HINE is used to assess motor milestones of the participants It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking.
Timepoint [1] 0 0
Day 302
Secondary outcome [2] 0 0
Part B Infantile-onset SMA: Change from Baseline in HINE Section 2 Motor Milestones Total Score - Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking.
Timepoint [2] 0 0
Baseline up to Day 302
Secondary outcome [3] 0 0
Part B Infantile-onset SMA: Time to Death or Permanent Ventilation - Permanent ventilation is defined as tracheostomy or = 16 hours of ventilation/day continuously for > 21 days in the absence of an acute reversible event.
Timepoint [3] 0 0
Screening up to Day 302
Secondary outcome [4] 0 0
Part B Infantile-onset SMA: Time to Death (Overall Survival)
Timepoint [4] 0 0
Screening up to Day 399
Secondary outcome [5] 0 0
Part A and B Later-onset SMA: Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score - HFMSE scale is a tool to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale was expanded to include 13 additional adapted items from the Gross Motor Function Measure to improve sensitivity for the higher functioning ambulant population.
Timepoint [5] 0 0
Baseline up to Day 302
Secondary outcome [6] 0 0
Part A and B Later-onset SMA: Change from Baseline in Revised Upper Limb Module (RULM) Score - 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.
Timepoint [6] 0 0
Baseline up to Day 302
Secondary outcome [7] 0 0
Part A and B Later-onset SMA: Total Number of New WHO Motor Milestones
Timepoint [7] 0 0
Baseline up to Day 302
Secondary outcome [8] 0 0
Part A and B Later-onset SMA: Change from Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) - ACEND is designed to quantify the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases. It includes domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance).
Timepoint [8] 0 0
Baseline up to Day 302
Secondary outcome [9] 0 0
Part A and B Later-onset SMA: Change from Baseline in Pediatric Quality of Life Inventory™ (PedsQL) - PedsQL is used to measure health related quality of life (HRQOL) in children and adolescents. The PedsQL Measurement 4.0 Generic Core Scales include assessment of physical functioning, emotional functioning, social functioning, and school functioning and the PedsQL 3.0 Neuromuscular Module measures HRQOL.
Timepoint [9] 0 0
Baseline up to Day 302
Secondary outcome [10] 0 0
Part B: Number of Participants with AEs and SAEs - 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 (including an abnormal assessment such as an abnormal laboratory value), 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.
Timepoint [10] 0 0
Screening up to Day 399
Secondary outcome [11] 0 0
Part B: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters
Timepoint [11] 0 0
Screening up to Day 302
Secondary outcome [12] 0 0
Part B: Number of Participants with Clinically Significant Shifts from Baseline in ECGs
Timepoint [12] 0 0
Day 1 up to Day 302
Secondary outcome [13] 0 0
Part B: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs
Timepoint [13] 0 0
Screening up to Day 302
Secondary outcome [14] 0 0
Part B: Change from Baseline in Body Length/Height
Timepoint [14] 0 0
Baseline up to Day 302
Secondary outcome [15] 0 0
Part B Infantile-onset SMA: Change from Baseline in Head Circumference
Timepoint [15] 0 0
Baseline up to Day 302
Secondary outcome [16] 0 0
Part B Infantile-onset SMA: Change from Baseline in Chest Circumference
Timepoint [16] 0 0
Baseline up to Day 302
Secondary outcome [17] 0 0
Part B Infantile-onset SMA: Change from Baseline in Arm Circumference
Timepoint [17] 0 0
Baseline up to Day 302
Secondary outcome [18] 0 0
Part B Later-onset SMA: Change from Baseline in Ulnar Length
Timepoint [18] 0 0
Baseline up to Day 302
Secondary outcome [19] 0 0
Part B: Ratio of Weight for Age
Timepoint [19] 0 0
Baseline up to Day 302
Secondary outcome [20] 0 0
Part B: Ratio of Weight for Length
Timepoint [20] 0 0
Baseline up to Day 302
Secondary outcome [21] 0 0
Part B: Ratio of Head-to-chest Circumference
Timepoint [21] 0 0
Baseline up to Day 302
Secondary outcome [22] 0 0
Part B: Change from Baseline in aPTT
Timepoint [22] 0 0
Baseline up to Day 279
Secondary outcome [23] 0 0
Part B: Change from Baseline in PT
Timepoint [23] 0 0
Baseline up to Day 279
Secondary outcome [24] 0 0
Part B: Change from Baseline in INR
Timepoint [24] 0 0
Baseline up to Day 279
Secondary outcome [25] 0 0
Part B: Change in Urine Total Protein
Timepoint [25] 0 0
Baseline up to Day 302
Secondary outcome [26] 0 0
Part B: Change from Baseline in Neurological Examination Outcomes
Timepoint [26] 0 0
Baseline up to Day 302
Secondary outcome [27] 0 0
Part B: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
Timepoint [27] 0 0
Baseline up to Day 302
Secondary outcome [28] 0 0
Part B: Percentage of Participants with a Postbaseline QTcF of > 500 msec and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of > 60 msec
Timepoint [28] 0 0
Baseline up to Day 302
Secondary outcome [29] 0 0
Part A, B and C: Number of Hospitalizations
Timepoint [29] 0 0
Day 1 to Day 302
Secondary outcome [30] 0 0
Part A, B and C: Duration of Hospitalizations
Timepoint [30] 0 0
Day 1 to Day 302
Secondary outcome [31] 0 0
Part A, B and C: Clinical Global Impression of Change (CGIC) - The CGIC scale is a 7 point scale that requires the clinician to assess how much the participant's illness has changed relative to a baseline state at the beginning of the intervention, where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. Higher rating will indicate worsening of the condition.
Timepoint [31] 0 0
Day 302
Secondary outcome [32] 0 0
Part A, B and C: Number of Participants with Serious Respiratory Events
Timepoint [32] 0 0
Screening up to Day 399
Secondary outcome [33] 0 0
Part B Infantile-onset SMA: Percentage of Time on Ventilation
Timepoint [33] 0 0
Screening up to Day 302
Secondary outcome [34] 0 0
Parts A, B and C: Ventilator Use
Timepoint [34] 0 0
Screening up to Day 302
Secondary outcome [35] 0 0
Parts A and B: Change from Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale - PASA questionnaire is developed to assess the signs and symptoms of dysphagia. It includes 33 items across 4 domains. General feeding, drinking liquids and eating solid foods will be assessed with 5 levels of response (Never, Rarely, Sometimes, Often, and Always), and 2 items will be assessed with 'Yes'/'No'. The assessment of swallowing concerns has 4 levels of response: Strongly Agree, Agree, Disagree, and Strongly Disagree. For Part A, it will be assessed in participants with later-onset SMA and in Part B, it will be assessed in participants with infantile- and later-onset SMA.
Timepoint [35] 0 0
Baseline up to Day 302
Secondary outcome [36] 0 0
Part C: Change from Baseline in HFMSE Score - HFMSE scale is a tool to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale was expanded to include 13 additional adapted items from the Gross Motor Function Measure to improve sensitivity for the higher functioning ambulant population.
Timepoint [36] 0 0
Baseline up to Day 302
Secondary outcome [37] 0 0
Part C: Change from Baseline in RULM Score - 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.
Timepoint [37] 0 0
Baseline up to Day 302
Secondary outcome [38] 0 0
Part C: Total Number of New WHO Motor Milestones
Timepoint [38] 0 0
Baseline up to Day 302
Secondary outcome [39] 0 0
Part C: Change from Baseline in ACEND - ACEND is designed to quantify the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases. It includes domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance).
Timepoint [39] 0 0
Baseline up to Day 302
Secondary outcome [40] 0 0
Part C: Change from Baseline in PedsQL™ - PedsQL is used to measure healthrelated quality of life (HRQOL) in children and adolescents. The PedsQL Measurement 4.0 Generic Core Scales include assessment of physical functioning, emotional functioning, social functioning, and school functioning and the PedsQL 3.0 Neuromuscular Module measures HRQOL.
Timepoint [40] 0 0
Baseline up to Day 302
Secondary outcome [41] 0 0
Part C: Change from Baseline in CHOP INTEND Total Score - 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.
Timepoint [41] 0 0
Baseline to up Day 302
Secondary outcome [42] 0 0
Part C: Change from Baseline in HINE Section 2 Motor Milestones Total Score - Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking.
Timepoint [42] 0 0
Baseline up to Day 302

Eligibility
Key inclusion criteria
Key

Part A, B and C:

- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound
heterozygote)

Part A:

- Onset of clinical signs and symptoms consistent with SMA at > 6 months (> 180 days) of
age (i.e., later-onset SMA)

- Age 2 to = 15 years, inclusive, at the time of informed consent

Part B:

- Participants with SMA symptom onset = 6 months (= 180 days) of age (infantile onset)
should have age > 1 week to = 7 months (= 210 days) at the time of informed consent

- Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):

- Age 2 to < 10 years at the time of informed consent

- Can sit independently but has never had the ability to walk independently

- HFMSE score = 10 and = 54 at Screening

Part C:

- Currently on nusinersen treatment at the time of Screening, with the first dose being at
least 1 year prior to Screening

Part C Cohort 1:

- Participants of any age (individuals =18 years of age at Screening must be ambulatory)

Part C Cohort 2:

- Participants =18 years of age at Screening (can be ambulatory or nonambulatory)

- HFMSE total score =4 points at Screening

- RULM entry item A score =3 points at Screening

Key
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Part A, B and C:

- Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy at any time during the Screening period

- Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or of an
implanted central nervous system (CNS) catheter

- Hospitalization for surgery, pulmonary event, or nutritional support within 2 months
prior to Screening or planned within 12 months after the participant's first dose

Part A:

- Respiratory insufficiency, defined by the medical necessity for invasive or
noninvasive ventilation for > 6 hours during a 24-hour period, at Screening

- Medical necessity for a gastric feeding tube

- Treatment with an investigational drug given for the treatment of SMA, 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
any survival motor neuron-2 (SMN2)-splicing modifier or gene therapy; or prior
antisense oligonucleotide treatment, or cell transplantation

Part B:

- Treatment with an investigational drug including but not limited to the treatment of
SMA, 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 any SMN2-splicing modifier or gene therapy; or prior antisense
oligonucleotide treatment, or cell transplantation

- Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):

- Respiratory insufficiency, defined by the medical necessity for invasive or
noninvasive ventilation for > 6 hours during a 24-hour period, at Screening

- Medical necessity for a gastric feeding tube

- Participants with SMA symptom onset = 6 months (= 180 days) of age (infantile onset):
Signs or symptoms of SMA present at birth or within the first week after birth

Part C:

- Concurrent or previous participation and/or administration of nusinersen in another
clinical study

- Concomitant or previous administration of any SMN2-splicing modifier (excluding
nusinersen) or gene therapy, either in a clinical study or as part of medical care.

- Concurrent or previous participation in any interventional investigational study for
any other drug or device within 30 days or 5 half-lives of the agent, whichever is
longer, prior to Screening

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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

Intervention assignment
Other
Other design features
Phase
Phase 2/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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
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
Minas Gerais
Country [9] 0 0
Brazil
State/province [9] 0 0
Rio Grande Do Sul
Country [10] 0 0
Brazil
State/province [10] 0 0
Sao Paulo
Country [11] 0 0
Canada
State/province [11] 0 0
British Columbia
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Colombia
State/province [13] 0 0
Bogota
Country [14] 0 0
Colombia
State/province [14] 0 0
Medellin
Country [15] 0 0
Estonia
State/province [15] 0 0
Tallinn
Country [16] 0 0
France
State/province [16] 0 0
Garches
Country [17] 0 0
France
State/province [17] 0 0
Toulouse cedex 9
Country [18] 0 0
Germany
State/province [18] 0 0
Baden Wuerttemberg
Country [19] 0 0
Germany
State/province [19] 0 0
Hessen
Country [20] 0 0
Greece
State/province [20] 0 0
Athens
Country [21] 0 0
Greece
State/province [21] 0 0
Thessaloniki
Country [22] 0 0
Hungary
State/province [22] 0 0
Budapest
Country [23] 0 0
Ireland
State/province [23] 0 0
Dublin
Country [24] 0 0
Israel
State/province [24] 0 0
Petach-Tikva
Country [25] 0 0
Israel
State/province [25] 0 0
Tel Aviv
Country [26] 0 0
Italy
State/province [26] 0 0
Milano
Country [27] 0 0
Italy
State/province [27] 0 0
Roma
Country [28] 0 0
Japan
State/province [28] 0 0
Fukuoka-Ken
Country [29] 0 0
Japan
State/province [29] 0 0
Hyogo-Ken
Country [30] 0 0
Japan
State/province [30] 0 0
Tokyo-To
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
Latvia
State/province [32] 0 0
Riga
Country [33] 0 0
Poland
State/province [33] 0 0
Gdansk
Country [34] 0 0
Poland
State/province [34] 0 0
Warszawa
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Ekaterinburg
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Moskva
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Valencia
Country [40] 0 0
Taiwan
State/province [40] 0 0
Kaohsiung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taipei
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Greater London

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to examine the clinical efficacy of nusinersen
administered intrathecally at higher doses to participants with spinal muscular atrophy
(SMA), as measured by change in Children's Hospital of Philadelphia Infant Test of
Neuromuscular Disorders (CHOP INTEND) total score (Part B); to examine the safety and
tolerability of nusinersen administered intrathecally at higher doses to participants with
SMA (Parts A and C).

The secondary objectives of this study are to examine the clinical efficacy of nusinersen
administered intrathecally at higher doses to participants with SMA (Parts A, B and C); to
examine the effect of nusinersen administered intrathecally at higher doses to participants
with SMA (Parts A and C); to examine the safety and tolerability of nusinersen administered
intrathecally at higher doses to participants with SMA, to examine the effect of nusinersen
administered intrathecally at higher doses compared to the currently approved dose in
participants with SMA (Part B).
Trial website
https://clinicaltrials.gov/show/NCT04089566
Trial related presentations / publications
Public notes

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
US Biogen Clinical Trial Center
Address 0 0
Country 0 0
Phone 0 0
866-633-4636
Fax 0 0
Email 0 0
clinicaltrials@biogen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04089566