Clinical trial NCT04729907: A Study to Learn About the Long-Term Safety of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Took Part in an Earlier Nusinersen Trial (ONWARD)
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2021-01-29
Enrollment: 115
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, researchers will learn more about the use of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study is an extension study and will enroll only those participants who have completed treatment in the parent study, 232SM203.

The main goal of the study is to learn about the long-term safety of nusinersen. The main questions researchers want to answer are:

* How many participants have adverse events and serious adverse events during the study?
* How do the results of electrocardiograms (ECGs), vital signs, and laboratory tests including blood and urine tests change after treatment?
* How many participants have a low platelet count after treatment?
* How many participants had a change in the time it took for their heart to recharge between beats after treatment?
* How does each participant's height and other measures of growth change after treatment?
* How much do the results of neurological exams that check movement, reflexes, and brain function change after treatment?

Researchers will also learn about the effect of nusinersen on mobility using various tests. They will study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing.

The 232SM302 study will be done as follows:

* Participants will be screened to check if they can join the study.
* Participants will receive their 1st dose of nusinersen in this study about 4 months after their final dose in the parent study.
* Each participant will receive nusinersen once every 4 months during the treatment period.
* Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back.
* The treatment period will last for up to 64 months (1921 days).
* There will be a follow-up safety period that lasts from 4 to 8 weeks.
* In total, participants will have up to 19 study visits. Participants will stay in the study for close to 6 years.

Detailed description: 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).

Eligibility criteria: Key Inclusion Criteria:

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

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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 1921
measure: Change from Baseline in Growth Parameters
timeFrame: Up to Day 1921
measure: Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
timeFrame: Up to Day 1921
measure: Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
timeFrame: Up to Day 1921
measure: Number of Participants With Shifts from Baseline in Vital Signs
timeFrame: Up to Day 1921
measure: Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
timeFrame: Up to Day 1921
measure: Change from Baseline in Prothrombin Time (PT)
timeFrame: Up to Day 1921
measure: Change from Baseline in International Normalized Ratio (INR)
timeFrame: Up to Day 1921
measure: Change from Baseline in Urine Total Protein
timeFrame: Up to Day 1921
measure: Change from Baseline in Neurological Examination Outcomes for Participants ≤2 Years of Age
timeFrame: Up to Day 1921
measure: Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age
timeFrame: Up to Day 1921
measure: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
timeFrame: Up to Day 1921
measure: 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
timeFrame: Up toDay 1921
Secondary outcomes:
measure: Total Number of New World Health Organization (WHO) Motor Milestones
timeFrame: Up to Day 1921
measure: Number of Participants Who Used Respiratory Support, by Type
timeFrame: Up to Day 1921
measure: Number of Hours Per Day of Respiratory Support
timeFrame: Up to Day 1921
measure: Number of Days That Respiratory Support Is Used
timeFrame: Up to Day 1921
measure: Time to Death (Overall Survival)
timeFrame: Up to Day 1921
measure: Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score
timeFrame: Up to Day 1921
measure: Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones
timeFrame: Up to Day 1921
measure: Percentage of HINE Section 2 Motor Milestone Responders
timeFrame: Up to Day 1921
measure: Percentage of Time Spent on Ventilation
timeFrame: Up to Day 1921
measure: Time to Death or Permanent Ventilation
timeFrame: Up to Day 1921
measure: Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
timeFrame: Up to Day 1921
measure: Change from Baseline in Revised Upper Limb Module (RULM) Score
timeFrame: Up to Day 1921
measure: Change From Baseline in Plasma Levels of Neurofilament (NF)
timeFrame: Up to Day 1921
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Plano
country: United States
facility: Children's Medical Center
state: Texas
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: São Paulo
country: Brazil
facility: Hospital das Clinicas - FMUSP
city: London
country: Canada
facility: London Health Sciences Centre (LHSC) - Children's Hospital
state: Ontario
city: Santiago
country: Chile
facility: Hospital Luis Calvo Mackenna
city: Santiago
country: Chile
facility: Clinica Las Condes
city: Santiago
country: Chile
facility: Clinica MEDS La Dehesa
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou Woman and Children's Medical Center
state: Guangdong
city: Hangzhou
country: China
facility: The Children's Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio
city: Tallinn
country: Estonia
facility: Tallinn Children's Hospital
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden Wuerttemberg
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH
state: Hessen
city: Milano
country: Italy
facility: Fondazione Serena Onlus - Centro Clinico Nemo
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka-Ken
city: Nishinomiya-shi
country: Japan
facility: Hyogo Medical University Hospital
state: Hyogo-Ken
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo-To
city: Beirut
country: Lebanon
facility: Saint George University Hospital Medical Center
city: Mexico
country: Mexico
facility: Instituto Nacional de Pediatria
state: Distrito Federal
city: Mexico
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
city: Ekaterinburg
country: Russian Federation
facility: Regional Pediatric Clinical Hospital #1
city: Moskva
country: Russian Federation
facility: Russian Children Neuromuscular Center of Veltischev
city: Dammam
country: Saudi Arabia
facility: King Fahad Specialist Hospital
city: Jeddah
country: Saudi Arabia
facility: National Guard Health Affairs: King Abdulaziz Medical City
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Esplugues Del Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: