Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy (DEVOTE)

Escalating Dose and Randomized, Controlled Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Muscular Atrophy, Spinal
• Intervention / Treatment: Drug: Nusinersen

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US Biogen Clinical Trial Center; Phone Number: 866-633-4636; Email: clinicaltrials@biogen.com
• Study Contact Backup: Name: Global Biogen Clinical Trial Center; Email: clinicaltrials@biogen.com

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • HC-UFMG - Hospital das Clinicas da Universidade Federal de Minas Gerais
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • Hospital das Clínicas da Faculdade de Medicina da USP
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • BC Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre (LHSC) - Children's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre/Glen Site/Montreal Children's Hospital
• Chile
  • Santiago, Chile, 7500539
    • Hospital Luis Calvo Mackenna
  • Santiago, Chile, 7591046
    • Clinica Las Condes
  • Santiago, Chile, 7691236
    • Clinica MEDS La Dehesa
• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100045
      • Beijing Children's Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400014
      • Children's Hospital Chongqing University of Medical Science
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510623
      • Guangzhou Woman and Children's Medical Center
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
  • Sichuan
    • Chendu, Sichuan, China, 610041
      • The Second Hospital affiliated to West China Medical University
• Colombia
  • Bogota, Colombia, 110231
    • Hospital Universitario San Ignacio
  • Medellin, Colombia, 050010
    • Fundacion Hospitalaria San Vicente de Paul
• Estonia
  • Tallinn, Estonia, 13419
    • Tallinn Children's Hospital
• France
  • Haute Garonne
    • Toulouse cedex 9, Haute Garonne, France, 31059
      • Hopital Purpan
  • Hauts De Seine
    • Garches, Hauts De Seine, France, 92380
      • Hôpital Raymond Poincaré
• Germany
  • Baden Wuerttemberg
    • Freiburg, Baden Wuerttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Universitaetsklinikum Giessen und Marburg GmbH
• Greece
  • Athens, Greece, 12462
    • University General Hospital "Attikon"
  • Thessaloniki, Greece, 54642
    • General Hospital of Thessaloniki "Hippokration"
• Hungary
  • Budapest, Hungary, 1094
    • Semmelweis Egyetem
  • Budapest, Hungary, 1146
    • Magyarorszagi Reformatus Egyhaz Bethesda Gyermekkorhaz
• Ireland
  • Dublin, Ireland, D01 XD99
    • The Children's University Hospital
• Israel
  • Petach-Tikva, Israel, 4920235
    • Schneider Children's Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Milano, Italy, 20162
    • Fondazione Serena Onlus - Centro Clinico Nemo
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli Irccs
• Japan
  • Fukuoka-Ken
    • Kurume-shi, Fukuoka-Ken, Japan, 830-0011
      • Kurume University Hospital
  • Hyogo-Ken
    • Nishinomiya-shi, Hyogo-Ken, Japan, 663-8501
      • Hyogo College of Medicine Hospital
  • Tokyo-To
    • Shinjuku-ku, Tokyo-To, Japan, 162-8666
      • Tokyo Women's Medical University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Gyeongsangbuk-do
    • Daegu, Gyeongsangbuk-do, Korea, Republic of, 41404
      • Kyungpook National University Chilgok Hospital
• Latvia
  • Riga, Latvia, LV- 1004
    • Children's Clinical University Hospital
• Lebanon
  • Beirut, Lebanon, 11 00 2807
    • Saint George University Hospital Medical Center
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 06720
      • Hospital Infantil de Mexico Federico Gomez
    • Mexico City, Distrito Federal, Mexico, 04530
      • Instituto Nacional de Pediatria
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • UMC Utrecht
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Warszawa, Poland, 04-730
    • Instytut Pomnik - Centrum Zdrowia Dziecka
• Russian Federation
  • Ekaterinburg, Russian Federation, 620149
    • Regional Pediatric Clinical Hospital #1
  • Moskva, Russian Federation, 125412
    • Russian Children Neuromuscular Center of Veltischev
• Saudi Arabia
  • Dammam, Saudi Arabia, 31444
    • King Fahad Specialist Hospital
  • Jeddah, Saudi Arabia, 21423
    • National Guard Health Affairs: King Abdulaziz Medical City
  • Riyadh, Saudi Arabia, 11211
    • King Faisal Specialist Hospital & Research Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • Esplugues Del Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey
  • Antalya, Turkey, 07070
    • Akdeniz Univesity Medical Faculty
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Hospital and Clinics
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

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 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 gene (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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Nusinersen; Administered as specified in the treatment arm; Other Names: BIIB058
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.	Drug: Nusinersen; Administered as specified in the treatment arm; Other Names: BIIB058
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.	Drug: Nusinersen; Administered as specified in the treatment arm; Other Names: BIIB058
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.	Drug: Nusinersen; Administered as specified in the treatment arm; Other Names: BIIB058

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to Day 183
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.	Screening up to Day 389
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters		Screening up to Day 302
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs)		Screening up to Day 302
Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs		Screening up to Day 302
Part A and C: Change from Baseline in Body Length/Height		Baseline up to Day 302
Part C Infantile-onset SMA: Change from Baseline in Head Circumference		Baseline up to Day 302
Part C Infantile-onset SMA: Change from Baseline in Chest Circumference		Baseline up to Day 302
Part C Infantile-onset SMA: Change from Baseline in Arm Circumference		Baseline up to Day 302
Part A and C Later-onset SMA: Change from Baseline in Ulnar Length		Baseline up to Day 302
Part A and C: Ratio of Weight for Age		Baseline up to Day 302
Part A and C: Ratio of Weight for Length		Baseline up to Day 302
Part C: Ratio of Head-to-chest Circumference		Baseline up to Day 302
Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT)		Baseline up to Day 269
Part A and C: Change from Baseline in Prothrombin Time (PT)		Baseline up to Day 269
Part A and C: Change from Baseline in International Normalized Ratio (INR)		Baseline up to Day 269
Part A and C: Change in Urine Total Protein		Baseline up to Day 302
Part A and C: Change from Baseline in Neurological Examination Outcomes		Baseline up to Day 302
Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements		Baseline up to Day 302
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		Baseline up to Day 302

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 302
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.	Baseline up to Day 302
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.	Screening up to Day 302
Part B Infantile-onset SMA: Time to Death (Overall Survival)		Screening up to Day 399
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.	Baseline up to Day 302
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.	Baseline up to Day 302
Part A and B Later-onset SMA: Total Number of New WHO Motor Milestones		Baseline up to Day 302
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).	Baseline up to Day 302
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.	Baseline up to Day 302
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.	Screening up to Day 399
Part B: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters		Screening up to Day 302
Part B: Number of Participants with Clinically Significant Shifts from Baseline in ECGs		Day 1 up to Day 302
Part B: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs		Screening up to Day 302
Part B: Change from Baseline in Body Length/Height		Baseline up to Day 302
Part B Infantile-onset SMA: Change from Baseline in Head Circumference		Baseline up to Day 302
Part B Infantile-onset SMA: Change from Baseline in Chest Circumference		Baseline up to Day 302
Part B Infantile-onset SMA: Change from Baseline in Arm Circumference		Baseline up to Day 302
Part B Later-onset SMA: Change from Baseline in Ulnar Length		Baseline up to Day 302
Part B: Ratio of Weight for Age		Baseline up to Day 302
Part B: Ratio of Weight for Length		Baseline up to Day 302
Part B: Ratio of Head-to-chest Circumference		Baseline up to Day 302
Part B: Change from Baseline in aPTT		Baseline up to Day 279
Part B: Change from Baseline in PT		Baseline up to Day 279
Part B: Change from Baseline in INR		Baseline up to Day 279
Part B: Change in Urine Total Protein		Baseline up to Day 302
Part B: Change from Baseline in Neurological Examination Outcomes		Baseline up to Day 302
Part B: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements		Baseline up to Day 302
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		Baseline up to Day 302
Part A, B and C: Number of Hospitalizations		Day 1 to Day 302
Part A, B and C: Duration of Hospitalizations		Day 1 to Day 302
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.	Day 302
Part A, B and C: Number of Participants with Serious Respiratory Events		Screening up to Day 399
Part B Infantile-onset SMA: Percentage of Time on Ventilation		Screening up to Day 302
Parts A, B and C: Ventilator Use		Screening up to Day 302
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.	Baseline up to Day 302
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.	Baseline up to Day 302
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.	Baseline up to Day 302
Part C: Total Number of New WHO Motor Milestones		Baseline up to Day 302
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).	Baseline up to Day 302
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.	Baseline up to Day 302
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.	Baseline to up Day 302
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.	Baseline up to Day 302

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

General Publications

• Finkel RS, Ryan MM, Pascual Pascual SI, Day JW, Mercuri E, De Vivo DC, Foster R, Montes J, Gurgel-Giannetti J, MacCannell D, Berger Z. Scientific rationale for a higher dose of nusinersen. Ann Clin Transl Neurol. 2022 Jun;9(6):819-829. doi: 10.1002/acn3.51562. Epub 2022 May 13.

Helpful Links

• Muscular Dystrophy Association
• SMA Europe
• CureSMA
• Study website - US patients only

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2020
• Primary Completion (Actual): February 21, 2024
• Study Completion (Estimated): June 4, 2024

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: 232SM203; 2019-002663-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No