Clinical trial NCT02594124: A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
Official title: An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Muscular Atrophy
Keywords: SMA
SMN
SMNRx
ISIS-SMNRx
ISIS 396443
SHINE
IONIS-SMNRx
IONIS-SMN Rx
Spinraza
nusinersen
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-11-01
Enrollment: 292
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to participants with Spinal Muscular Atrophy (SMA) who previously participated in investigational studies of nusinersen. The secondary objective is to examine the long-term efficacy of nusinersen administered by IT injection to participants with SMA who previously participated in investigational studies of nusinersen.

Detailed description: This study was initiated and the protocol was registered by Ionis Pharmaceuticals, Inc.

In August 2016, Biogen assumed responsibility for this study.

Eligibility criteria: Key Inclusion Criteria:

* Signed informed consent of parent or guardian and signed informed assent of participant, if indicated per participant's age and institutional guidelines.
* Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks

Key Exclusion Criteria:

* Have any condition or worsening condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
* Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
* Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
* Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer

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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants With Vital Sign Abnormalities Reported as AEs
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants With Weight Abnormalities Reported as AEs
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants With Neurological Abnormalities Reported as AEs
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants With Laboratory Abnormalities Reported as AEs
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants With Coagulation Parameters Reported as AEs
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants With Clinically Significant Shifts in12 Lead Electrocardiogram (ECG) Results
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
measure: Number of Participants Taking Any Concomitant Medication
timeFrame: From Day 1 up to the end of the study (up to 2848 days)
Secondary outcomes:
measure: Mean Number of New Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria
timeFrame: MMDR Period: At Day 1800
measure: Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)
timeFrame: At Day 309
measure: Number of Participants Who Died or Met Permanent Ventilation
timeFrame: MMDR Period: Up to Day 1800
measure: Number of Participants Not Requiring Permanent Ventilation
timeFrame: MMDR Period: Up to Day 1800
measure: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale
timeFrame: Baseline, Day 2198
measure: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score
timeFrame: MMDR Period: Baseline, MMDR Day 1800
measure: Change From Baseline in Revised Upper Limb Module (RULM) Total Score
timeFrame: MMDR Period: Baseline, MMDR Day 1800
measure: Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT)
timeFrame: Baseline, Day 2670
measure: Number of Participants Who Experienced Contracture Assesment
timeFrame: MMDR Period: At MMDR Day 1800
measure: Change From Baseline in Compound Muscular Action Potential (CMAP)
timeFrame: MMDR Period: Baseline, MMDR Day 1800
measure: Change From Baseline in Body Length
timeFrame: MMDR Period: up to Day 1800
measure: Change From Baseline in Weight
timeFrame: MMDR Period: up to Day 1800
measure: Change From Baseline in Weight for Age Percentile
timeFrame: MMDR Period: up to Day 1800
measure: Percentage of CMAP Responders
timeFrame: MMDR Period: At Day 1800
measure: Number of Participants Who Achieved Motor Milestones
timeFrame: MMDR Period: up to Day 1800
measure: Number of Participants Who Achieved Standing Alone and Walking With Assistance
timeFrame: MMDR Period: up to Day 1800
measure: Total Number of Hospitalizations Due to Serious Respiratory Events
timeFrame: Up to day 2520
measure: Total Number of Hospitalizations Due to Serious Adverse Events
timeFrame: Up to day 2520
measure: Percent of Time in Hospitalization
timeFrame: Upto day 2160
measure: Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine by Visit
timeFrame: MMDR Period: Baseline, MMDR Day 1800
measure: Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain
timeFrame: MMDR Period: At Day 1800
measure: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) Questionnaire Total Score
timeFrame: MMDR Period: up to Day 1800
measure: Number of Participants With Disease-related Hospitalizations and AEs
timeFrame: MMDR Period: up to Day 1800
measure: Survival Rate
timeFrame: MMDR Period: up to Day 1800
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: New York
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: Saint Paul
country: United States
facility: Gillette Children's Specialty Healthcare
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Miyagi
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Durham
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
city: Obu, Aichi
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Sydney
country: Australia
facility: Sydney Children's Hospital Clinical Research Centre
state: New South Wales
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Brussels
country: Belgium
facility: Universitair Kinderziekenhuis Koningin Fabiola
city: Vancouver
country: Canada
facility: BC Children's Hospital / UBC
state: British Columbia
city: Brussel
country: Canada
facility: Children's Health Research Institute
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Paris
country: France
facility: Armand Trousseau Hospital, I-Motion
state: Paris 9
city: Muenchen
country: Germany
facility: LMU-Campus Innenstadt
state: Bayern
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
state: Hong Kong SAR
city: Essen
country: Italy
facility: Pediatric Neurology Unit, Catholic University
city: Genova
country: Italy
facility: Istituto Giannina Gaslini, Centro Traslazionale di Miologia
city: Messina
country: Italy
facility: Department of Neuroscience, Università di Messina, AOU Polic
city: Obu
country: Japan
facility: Aichi Children's Health and Medical Center
state: Aichi
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine
state: Hyogo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University
state: Tokyo
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Miyagi
country: Japan
facility: Miyagi Prefectural Children Hospital
city: Miyazaki
country: Japan
facility: University of Miyazaki Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Korea
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Hebron
country: Spain
facility: Hospital Universitario Vall de Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Gothenburg
country: Sweden
facility: The Queen Silvia Children's Hospital
city: Ankara
country: Turkey
facility: Uníversity of Hacettepe
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Newcastle
country: United Kingdom
facility: MRC Centre for Neuromuscular Diseases at Newcastle
state: Northumberland
city: London
country: United Kingdom
facility: UCL Institute of Child Health
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: