Back to resultsA Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (NURTURE)
Primary Purpose
Spinal Muscular Atrophy
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nusinersen
Sponsored by
About this trial
This is an interventional prevention trial for Spinal Muscular Atrophy focused on measuring NURTURE
Eligibility Criteria
Key Inclusion Criteria:
- Age ≤ 6 weeks at first dose.
- Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
- Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).
- Ulnar compound muscle action potential (CMAP) ≥ 1 mV at Baseline.
- Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42 weeks for twins.
- Meet additional study related criteria.
Key Exclusion Criteria:
- Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support).
- Any clinical signs or symptoms at Screening or immediately prior to the first dosing (Day 1) that are, in the opinion of the Investigator, strongly suggestive of SMA.
- Clinically significant abnormalities in hematology or clinical chemistry parameters.
- Treatment with an investigational drug given for the treatment of SMA biological agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.
- Meet additional study related criteria.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- David Geffen School of Medicine
- University of California Davis Health System
- Children's Hospital Colorado
- Nemours Children's Hospital, Orlando
- Ann & Robert H. Lurie Children's Hospital of Chicago
- The Johns Hopkins Hospital
- Massachusetts General Hospital
- Columbia University
- The Children's Hospital of Philadelphia
- University of Utah
- Seattle Children's Research Institute
- Hospital de Pediatria Dr. J. P. Garrahan
- Queensland Children's Hospital
- Royal Children's Hospital
- University of Calgary - Alberta Children's Hospital
- Universitaetsklinikum Freiburg
- Tel Aviv Sourasky Medical Center
- Ospedale Pediatrico Bambino Gesù
- Fondazione Serena Onlus - Centro Clinico Nemo
- Hamad General Hospital
- Kaohsiung Medical University Chung-Ho Memorial Hospital
- National Taiwan University Hospital
- Hacettepe University Medical Faculty
- Yeditepe University Medical School Hospital
- Great Ormond Street Hospital for Children
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nusinersen
Arm Description
Nusinersen administered as an intrathecal injection
Outcomes
Primary Outcome Measures
Time to death or respiratory intervention
The time will be the age of the participant at the first occurrence of either a respiratory intervention or death. Respiratory intervention is defined as invasive or noninvasive ventilation for ≥6 hours/day continuously for 7 or more days OR tracheostomy.
Secondary Outcome Measures
Percentage of participants developing clinically manifested spinal muscular atrophy (SMA)
Percentage of participants alive
Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE)
Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE)
Change from Baseline in weight for age/length
Change from Baseline in head circumference
Change from Baseline in chest circumference ratio
Change from Baseline in head to chest circumference ratio
Change from Baseline in arm circumference ratio
Incidence of adverse events (AEs) and/or serious adverse events (SAEs)
Change from Baseline in clinical laboratory parameters
Assessed by the following laboratory tests: Hematology: red blood cells, hemoglobin, hematocrit, platelets, white blood cells, white blood cell differential, Blood chemistry: total protein, albumin, creatinine, cystatin C, creatine phosphokinase, blood urea nitrogen, total bilirubin (direct and indirect), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glucose, calcium, phosphorous, chloride, sodium, potassium. Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, red blood cells, white blood cells, epithelial cells, bacteria, casts, crystals
Change from Baseline in electrocardiograms (ECGs)
Change from Baseline in vital signs
Vital sign will be assessed by: temperature, pulse rate, resting systolic and diastolic blood pressure, and respiratory rate.
Change from Baseline in neurological examinations
Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02386553
Brief Title
A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
Acronym
NURTURE
Official Title
An Open-Label Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Subjects With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 18, 2015 (Actual)
Primary Completion Date
January 27, 2025 (Anticipated)
Study Completion Date
January 27, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is to examine the efficacy of multiple doses of Nusinersen administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA). Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic SMA.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Muscular Atrophy
Keywords
NURTURE
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nusinersen
Arm Type
Experimental
Arm Description
Nusinersen administered as an intrathecal injection
Intervention Type
Drug
Intervention Name(s)
Nusinersen
Other Intervention Name(s)
ISIS 396443, BIIB058, ISIS SMNRx, Spinraza
Intervention Description
Solution for intrathecal injection
Primary Outcome Measure Information:
Title
Time to death or respiratory intervention
Description
The time will be the age of the participant at the first occurrence of either a respiratory intervention or death. Respiratory intervention is defined as invasive or noninvasive ventilation for ≥6 hours/day continuously for 7 or more days OR tracheostomy.
Time Frame
Up to Day 2891
Secondary Outcome Measure Information:
Title
Percentage of participants developing clinically manifested spinal muscular atrophy (SMA)
Time Frame
At 13 and 24 months of age
Title
Percentage of participants alive
Time Frame
At 13 months, and 2, 3, 4, 5, 6, 7 and 8 years of age
Title
Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE)
Time Frame
At 13 and 24 months of age
Title
Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
Time Frame
Up to Day 2891
Title
Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
Time Frame
Up to Day 2891
Title
Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE)
Time Frame
Up to Day 2891
Title
Change from Baseline in weight for age/length
Time Frame
Up to Day 2891
Title
Change from Baseline in head circumference
Time Frame
Up to Day 2891
Title
Change from Baseline in chest circumference ratio
Time Frame
Up to Day 2891
Title
Change from Baseline in head to chest circumference ratio
Time Frame
Up to Day 2891
Title
Change from Baseline in arm circumference ratio
Time Frame
Up to Day 2891
Title
Incidence of adverse events (AEs) and/or serious adverse events (SAEs)
Time Frame
Up to Day 2891
Title
Change from Baseline in clinical laboratory parameters
Description
Assessed by the following laboratory tests: Hematology: red blood cells, hemoglobin, hematocrit, platelets, white blood cells, white blood cell differential, Blood chemistry: total protein, albumin, creatinine, cystatin C, creatine phosphokinase, blood urea nitrogen, total bilirubin (direct and indirect), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glucose, calcium, phosphorous, chloride, sodium, potassium. Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, red blood cells, white blood cells, epithelial cells, bacteria, casts, crystals
Time Frame
Up to Day 2891
Title
Change from Baseline in electrocardiograms (ECGs)
Time Frame
Up to Day 2891
Title
Change from Baseline in vital signs
Description
Vital sign will be assessed by: temperature, pulse rate, resting systolic and diastolic blood pressure, and respiratory rate.
Time Frame
Up to Day 2891
Title
Change from Baseline in neurological examinations
Time Frame
Up to Day 2891
Title
Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations
Time Frame
Up to Day 2801
10. Eligibility
Sex
All
Maximum Age & Unit of Time
6 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Age ≤ 6 weeks at first dose.
Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).
Ulnar compound muscle action potential (CMAP) ≥ 1 mV at Baseline.
Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42 weeks for twins.
Meet additional study related criteria.
Key Exclusion Criteria:
Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support).
Any clinical signs or symptoms at Screening or immediately prior to the first dosing (Day 1) that are, in the opinion of the Investigator, strongly suggestive of SMA.
Clinically significant abnormalities in hematology or clinical chemistry parameters.
Treatment with an investigational drug given for the treatment of SMA biological agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.
Meet additional study related criteria.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California Davis Health System
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Nemours Children's Hospital, Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2605
Country
United States
Facility Name
The Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Seattle Children's Research Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Hospital de Pediatria Dr. J. P. Garrahan
City
Ciudad Autonoma Buenos Aires
ZIP/Postal Code
C1245AAM
Country
Argentina
Facility Name
Queensland Children's Hospital
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
University of Calgary - Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
Universitaetsklinikum Freiburg
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Roma
State/Province
Lazio
ZIP/Postal Code
165
Country
Italy
Facility Name
Fondazione Serena Onlus - Centro Clinico Nemo
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Hamad General Hospital
City
Doha
ZIP/Postal Code
3050
Country
Qatar
Facility Name
Kaohsiung Medical University Chung-Ho Memorial Hospital
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Hacettepe University Medical Faculty
City
Ankara
ZIP/Postal Code
6230
Country
Turkey
Facility Name
Yeditepe University Medical School Hospital
City
Istanbul
ZIP/Postal Code
31755
Country
Turkey
Facility Name
Great Ormond Street Hospital for Children
City
London
State/Province
Greater London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
27939059
Citation
Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, Yamashita M, Rigo F, Hung G, Schneider E, Norris DA, Xia S, Bennett CF, Bishop KM. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017-3026. doi: 10.1016/S0140-6736(16)31408-8. Epub 2016 Dec 7.
Results Reference
derived
Learn more about this trial
A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
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