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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02386553




Registration number
NCT02386553
Ethics application status
Date submitted
27/02/2015
Date registered
12/03/2015
Date last updated
3/12/2019

Titles & IDs
Public title
A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
Scientific 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.
Secondary ID [1] 0 0
2014-002098-12
Secondary ID [2] 0 0
232SM201
Universal Trial Number (UTN)
Trial acronym
NURTURE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Nusinersen

Experimental: Nusinersen - Nusinersen administered as an intrathecal injection


Treatment: Drugs: Nusinersen
Solution for intrathecal injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to Day 2891
Secondary outcome [1] 0 0
Percentage of participants developing clinically manifested spinal muscular atrophy (SMA).
Timepoint [1] 0 0
At 13 and 24 months of age
Secondary outcome [2] 0 0
Percentage of participants alive
Timepoint [2] 0 0
At 13 months, and 2, 3, 4, 5, 6, 7 and 8 years of age
Secondary outcome [3] 0 0
Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE)
Timepoint [3] 0 0
At 13 and 24 months of age
Secondary outcome [4] 0 0
Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
Timepoint [4] 0 0
Up to Day 2891
Secondary outcome [5] 0 0
Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
Timepoint [5] 0 0
Up to Day 2891
Secondary outcome [6] 0 0
Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE)
Timepoint [6] 0 0
Up to Day 2891
Secondary outcome [7] 0 0
Change from Baseline in weight for age/length
Timepoint [7] 0 0
Up to Day 2891
Secondary outcome [8] 0 0
Change from Baseline in head circumference
Timepoint [8] 0 0
Up to Day 2891
Secondary outcome [9] 0 0
Change from Baseline in chest circumference ratio
Timepoint [9] 0 0
Up to Day 2891
Secondary outcome [10] 0 0
Change from Baseline in head to chest circumference ratio
Timepoint [10] 0 0
Up to Day 2891
Secondary outcome [11] 0 0
Change from Baseline in arm circumference ratio
Timepoint [11] 0 0
Up to Day 2891
Secondary outcome [12] 0 0
Incidence of adverse events (AEs) and/or serious adverse events (SAEs)
Timepoint [12] 0 0
Up to Day 2891
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Up to Day 2891
Secondary outcome [14] 0 0
Change from Baseline in electrocardiograms (ECGs)
Timepoint [14] 0 0
Up to Day 2891
Secondary outcome [15] 0 0
Change from Baseline in vital signs - Vital sign will be assessed by: temperature, pulse rate, resting systolic and diastolic blood pressure, and respiratory rate.
Timepoint [15] 0 0
Up to Day 2891
Secondary outcome [16] 0 0
Change from Baseline in neurological examinations
Timepoint [16] 0 0
Up to Day 2891
Secondary outcome [17] 0 0
Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations.
Timepoint [17] 0 0
Up to Day 2801

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
No limit
Maximum age
6 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Prevention
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Canada
State/province [8] 0 0
Alberta
Country [9] 0 0
Germany
State/province [9] 0 0
Baden-Württemberg
Country [10] 0 0
Italy
State/province [10] 0 0
Lazio
Country [11] 0 0
Italy
State/province [11] 0 0
Milano
Country [12] 0 0
Qatar
State/province [12] 0 0
Doha
Country [13] 0 0
Taiwan
State/province [13] 0 0
Kaohsiung City
Country [14] 0 0
Taiwan
State/province [14] 0 0
Taipei
Country [15] 0 0
Turkey
State/province [15] 0 0
Sihhiye

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02386553
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications