A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies

Spinal Muscular Atrophy Clinical Trial

— SHINE  

Official title:

An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02594124
• Other study ID #: ISIS 396443-CS11
• Secondary ID: 2015-001870-16
• Status: Completed
• Phase: Phase 3
• Start date: November 4, 2015
• Est. completion date: August 21, 2023

Study information

• Verified date: February 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to evaluate the 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.

Description:

This study was initiated and the protocol was registered by Ionis Pharmaceuticals, Inc. In August 2016, Biogen assumed responsibility for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 292
• Est. completion date: August 21, 2023
• Est. primary completion date: August 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Drug:
• nusinersen
Administered by intrathecal (IT) injection

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Sydney Children's Hospital Clinical Research Centre	Sydney	New South Wales
Belgium	Universitair Kinderziekenhuis Koningin Fabiola	Brussels
Canada	Children's Health Research Institute	Brussel	Ontario
Canada	McGill University Health Centre	Montreal	Quebec
Canada	BC Children's Hospital / UBC	Vancouver	British Columbia
France	Armand Trousseau Hospital, I-Motion	Paris	Paris 9
Germany	Universitatsklinikum Essen	Essen
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	LMU-Campus Innenstadt	Muenchen	Bayern
Hong Kong	The University of Hong Kong	Hong Kong	Hong Kong SAR
Italy	Pediatric Neurology Unit, Catholic University	Essen
Italy	Istituto Giannina Gaslini, Centro Traslazionale di Miologia	Genova
Italy	Department of Neuroscience, Università di Messina, AOU Polic	Messina
Japan	Kumamoto University Hospital	Kumamoto
Japan	Miyagi Prefectural Children Hospital	Miyagi
Japan	University of Miyazaki Hospital	Miyazaki
Japan	Hyogo College of Medicine	Nishinomiya	Hyogo
Japan	Aichi Children's Health and Medical Center	Obu	Aichi
Japan	Tokyo Women's Medical University	Shinjuku-ku	Tokyo
Korea, Republic of	Seoul National University Hospital	Seoul	Korea
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Universitario Vall de Hebron	Hebron
Spain	Hospital Universitario La Paz	Madrid
Sweden	The Queen Silvia Children's Hospital	Gothenburg
Turkey	Uníversity of Hacettepe	Ankara
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul
United Kingdom	UCL Institute of Child Health	London
United Kingdom	MRC Centre for Neuromuscular Diseases at Newcastle	Newcastle	Northumberland
United States	Children's Hospital Colorado	Aurora	Colorado
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Children's Medical Center	Dallas	Texas
United States	Duke University School of Medicine	Durham	North Carolina
United States	Oregon Health Sciences University	Durham	Oregon
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Duke University School of Medicine	Miyagi	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	New York	Illinois
United States	Columbia University Medical Center	New York	New York
United States	University of Utah	Obu, Aichi	Utah
United States	Nemours Children's Clinic	Orlando	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs)		Up to Day 1814
Primary	Number of participants with clinically significant vital sign abnormalities		Up to Day 1814
Primary	Number of participants with clinically significant weight abnormalities		Up to Day 1814
Primary	Number of participants with clinically significant neurological examination abnormalities		Up to Day 1814
Primary	Number of participants with clinically significant laboratory assessment abnormalities		Up to Day 1814
Primary	Number of participants with clinically significant coagulation parameter abnormalities		Up to Day 1814
Primary	Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities		Up to Day 1814
Primary	Change from Baseline in concomitant medications		Up to Day 1814
Secondary	Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria		Up to Day 1814
Secondary	Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)		Up to Day 1814
Secondary	Time to death or permanent ventilation		Up to Day 1814
Secondary	Percentage of participants not requiring permanent ventilation		Up to Day 1814
Secondary	Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale	CHOP-INTEND tests includes 16 items 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.	Up to Day 1814
Secondary	Change from Baseline in Hammersmith Functional Motor Scale	The HFMSE tests motor function of participants 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.	Up to Day 1814
Secondary	Change from Baseline in Revised Upper Limb Module (RULM)		Up to Day 1814
Secondary	Change from Baseline in 6-Minute Walk Test (6MWT)	6MWT: walking up and down a 25 meter track without aids or orthotics as fast as possible for 6 minutes. Lap splits, minute splits and total distance are recorded, in addition to any rests and falls.	Up to Day 1814
Secondary	Change from Baseline in Compound Muscular Action Potential (CMAP)	CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles.	Up to Day 1814
Secondary	Change from Baseline in body length and/or height (for all participants)		Up to Day 1814
Secondary	Change from Baseline in head circumference (for participants up to 36 months of age)		Up to Day 1814
Secondary	Change from Baseline in chest circumference (for participants up to 36 months of age)		Up to Day 1814
Secondary	Change from Baseline in arm circumference (for participants up to 36 months of age)		Up to Day 1814
Secondary	Proportion of CMAP responders		Up to Day 1814
Secondary	Number of participants with motor milestones achieved		Up to Day 1814
Secondary	Proportion of participants who achieved standing alone		Up to Day 1814
Secondary	Proportion of participants who achieved walking with assistance		Up to Day 1814
Secondary	Number of participants with serious respiratory events		Up to Day 1814
Secondary	Number of participants hospitalized		Up to Day 1814
Secondary	Duration of hospitalizations		Up to Day 1814
Secondary	Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine		Up to Day 1814
Secondary	Change from Baseline in Quality of Life (QOL) Questionnaires		Up to Day 1814
Secondary	Number of Disease-related hospitalizations and AEs		Up to Day 1814
Secondary	Overall survival rate		Up to Day 1814

External Links

•   Cure SMA
•   Muscular Dystrophy Association
•   National Organization for Rare Diseases