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

NCT02594124 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ISIS 396443-CS112015-001870-16
• Study Type: interventional
• Target: 292
• Locations: 14 countries
• Sites: 47

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.

Conditions

Spinal Muscular Atrophy

Keywords

SMA; SMN; SMNRx; ISIS-SMNRx; ISIS 396443; SHINE; IONIS-SMNRx; IONIS-SMN Rx; Spinraza; nusinersen

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  AE:unfavorable and unintended sign, symptom, or disease temporally associated with study/use of an investigational drug, whether or not it's considered related to investigational drug. SAE:AE that in view of either Investigator/Sponsor, meets any of the following criteria: results in death;is life-threatening:i.e.poses risk of death, hospitalization/it's prolongation;results in a persistent or significant incapacity or substantial disruption of normal life functions;results in congenital anomaly or birth defect in offspring;is an important event in the opinion of Investigator/Sponsor. TEAE: if it was present prior to first dose of nusinersen or first sham procedure in index study and subsequently worsened in severity/was not present prior to first dose of nusinersen or first sham procedure in index study but subsequently appeared.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants With Vital Sign Abnormalities Reported as AEs

  The vital sign assessments included blood pressure, temperature, pulse rate, and respiratory rate. Participants with abnormalities in these assessments recorded as AEs were reported.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants With Weight Abnormalities Reported as AEs

  Weight decrease was characterized by a decrease of \>=7% from baseline and weight increase was characterized by an increase of \>=7% from baseline. Participants with these abnormalities recorded as AEs were reported.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants With Neurological Abnormalities Reported as AEs

  Participants with abnormalities in neurological examinations recorded as AEs were reported.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants With Laboratory Abnormalities Reported as AEs

  Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs were reported.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants With Coagulation Parameters Reported as AEs

  Coagulation parameters included activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Participants with abnormalities in these coagulation parameters recorded as AEs were reported.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants With Clinically Significant Shifts in12 Lead Electrocardiogram (ECG) Results

  Clinical significance of abnormalities in 12 lead ECG was determined based on the investigator's discretion.

  From Day 1 up to the end of the study (up to 2848 days)

• Number of Participants Taking Any Concomitant Medication

  A concomitant therapy is any non-protocol-specified drug or substance (including over-the-counter medications, herbal medications, and vitamin supplements) administered between the beginning of screening and the last telephone contact or study visit.

  From Day 1 up to the end of the study (up to 2848 days)

Secondary Outcomes (24)

• Mean Number of New Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria

  MMDR Period: At Day 1800

• Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)

  At Day 309

• Number of Participants Who Died or Met Permanent Ventilation

  MMDR Period: Up to Day 1800

• Number of Participants Not Requiring Permanent Ventilation

  MMDR Period: Up to Day 1800

• Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale

  Baseline, Day 2198

Study Arms (5)

Group 1

EXPERIMENTAL

Participants transitioned from ISIS 396443-CS3B (NCT02193074)

Drug: nusinersen

Group 2

EXPERIMENTAL

Participants transitioned from ISIS 396443-CS4 (NCT02292537)

Drug: nusinersen

Group 3

EXPERIMENTAL

Participants transitioned from ISIS 396443-CS12 (NCT02052791)

Drug: nusinersen

Group 4

EXPERIMENTAL

Participants transitioned from ISIS 396443-CS3A (NCT01839656)

Drug: nusinersen

Group 5

EXPERIMENTAL

Participants transitioned from 232SM202 (NCT02462759)

Drug: nusinersen

Interventions

nusinersen DRUG

Administered by intrathecal (IT) injection

Also known as: ISIS 396443, Spinraza, BIIB058, IONIS SMN Rx, ISIS SMNRx

Group 1; Group 2; Group 3; Group 4; Group 5

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (47)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095-8344, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94305, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Nemours Children's Clinic

Orlando, Florida, 32827, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

New York, Illinois, 60611, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27710, United States

Location

Duke University School of Medicine

Miyagi, North Carolina, 27710, United States

Location

Oregon Health Sciences University

Durham, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

University of Utah

Obu, Aichi, Utah, 84112, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Sydney Children's Hospital Clinical Research Centre

Sydney, New South Wales, 2031, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Universitair Kinderziekenhuis Koningin Fabiola

Brussels, 1020, Belgium

Location

BC Children's Hospital / UBC

Vancouver, British Columbia, V6H 3V4, Canada

Location

Children's Health Research Institute

Brussel, Ontario, N6A 5W9, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Armand Trousseau Hospital, I-Motion

Paris, Paris 9, 75012, France

Location

LMU-Campus Innenstadt

Munich, Bavaria, 80337, Germany

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

The University of Hong Kong

Hong Kong, Hong Kong SAR, 999077, Hong Kong

Location

Pediatric Neurology Unit, Catholic University

Essen, 00168, Italy

Location

Istituto Giannina Gaslini, Centro Traslazionale di Miologia

Genova, 16147, Italy

Location

Department of Neuroscience, Università di Messina, AOU Polic

Messina, 98125, Italy

Location

Aichi Children's Health and Medical Center

Ōbu, Aichi-ken, 474-0038, Japan

Location

Hyogo College of Medicine

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Tokyo Women's Medical University

Shinjuku-ku, Tokyo, 162-8666, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Miyagi Prefectural Children Hospital

Miyagi, 989-3126, Japan

Location

University of Miyazaki Hospital

Miyazaki, 889-1692, Japan

Location

Seoul National University Hospital

Seoul, Korea, 3080, South Korea

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

Hospital Universitario Vall de Hebron

Hebron, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

The Queen Silvia Children's Hospital

Gothenburg, SE 416 86, Sweden

Location

Uníversity of Hacettepe

Ankara, 6100, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital

Istanbul, 34662, Turkey (Türkiye)

Location

MRC Centre for Neuromuscular Diseases at Newcastle

Newcastle, Northumberland, NE1 3BZ, United Kingdom

Location

UCL Institute of Child Health

London, WC1N 1EH, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

nusinersen

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: During the blinded loading period, the following participants will be masked: * Key site personnel (Investigator, Study Coordinator, and Outcomes Assessors) * Participant * The sponsor After the loading period has been completed, subsequent doses will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 30, 2015
• First Posted: November 2, 2015
• Study Start: November 4, 2015
• Primary Completion: August 21, 2023
• Study Completion: August 21, 2023
• Last Updated: October 22, 2024
• Results First Posted: October 22, 2024

Record last verified: 2024-09

Locations

ES (3); SE (1); AU (2); GB (2); HK (1); DE (3); TU (2); US (18); BE (1); FR (1); IT (3); JP (6); KR (1); CA (3)