A Study of Multiple Doses of ISIS ISIS 396443 Delivered to Infants with Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

• Register: EUCTR
• Last refreshed on: 8 January 2018
• Main ID: EUCTR2014-002098-12-GB
• Date of registration: 30/03/2015
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: A Study of Multiple Doses of ISIS 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 - NURTURE
• Date of first enrolment: 10/06/2015
• Target sample size: 25
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002098-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Germany, Italy, Qatar, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion criteria

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 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 25
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy (SMA)
MedDRA version: 20.1 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Spinraza
Product Name: Spinraza
Product Code: ISIS 396443 (BIIB058)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Nusinersen
CAS Number: 1258984-36-9
Current Sponsor code: ISIS 396443 (BIIB058)
Other descriptive name: ISIS 396443 (BIIB058)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.4-

Primary Outcome(s)

Main Objective: 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).

Timepoint(s) of evaluation of this end point: Up to Day 1820

Primary end point(s): 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 Objective: Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic SMA.

Secondary Outcome(s)

Secondary end point(s): 1 Percentage of participants developing clinically manifested spinal muscular trophy(SMA)
2 Percentage of participants alive
3 Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE)
4 Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
5 Change from Baseline in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
6 Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE)
7 Change from Baseline in weight for age/length
8 Change from Baseline in head circumference
9 Change from Baseline in chest circumference ratio
10 Change from Baseline in head to chest circumference ratio
11 Change from Baseline in arm circumference ratio
12 Incidence of adverse events (AEs) and/or serious adverse events (SAEs).
13 Change from Baseline in clinical laboratory parameters
14 Change from Baseline in electrocardiograms (ECGs)
15 Change from Baseline in vital signs
16 Change from Baseline in neurological examinations
17 Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations

Timepoint(s) of evaluation of this end point: Points 1, 3 and 4 will be measured at 13 and 24 months of age
Point 2 will be measured at 13 months, and 2, 3, 4 and 5 years of age
Point 5 to 16 inclusive will be measured up to Day 1820
Point 17 will be measured up to Day 1730

Secondary ID(s)

232SM201

NCT02386553

2014-002098-12-IT

Source(s) of Monetary Support

Biogen Idec Research Limited