A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

NCT02386553 | Completed Phase 2 Results DMC

• 2 other identifiers: 232SM2012014-002098-12
• Study Type: interventional
• Target: 25
• Locations: 7 countries
• Sites: 21

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.

Conditions

Spinal Muscular Atrophy

Keywords

NURTURE

Outcome Measures

Primary Outcomes (1)

• Time to Death or Respiratory Intervention

  The time was the age of the participant at the first occurrence of either a respiratory intervention or death. Respiratory intervention was defined as invasive or noninvasive ventilation for ≥6 hours/day continuously for 7 or more days OR tracheostomy.

  Screening up to Day 2891

Secondary Outcomes (27)

• Proportion of Participants Developing Clinically Manifested Spinal Muscular Atrophy (SMA)

  At 13 and 24 months of age

• Percentage of Participants Alive

  Up to 8 years of age

• Percentage of Participants Who Attained Motor Milestones Assessed as Part of the Hammersmith Infant Neurological Examination (HINE)

  Day 700

• Percentage of Participants Who Attained Motor Milestones as Assessed by World Health Organization (WHO) Criteria

  Baseline up to Day 2891

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

  Baseline, Day 2891

Study Arms (1)

Nusinersen

EXPERIMENTAL

Nusinersen administered as an intrathecal injection

Drug: Nusinersen

Interventions

Nusinersen DRUG

Solution for intrathecal injection

Also known as: ISIS 396443, BIIB058, ISIS SMNRx, Spinraza

Nusinersen

Eligibility Criteria

• Age: 0 Weeks - 6 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (21)

David Geffen School of Medicine

Los Angeles, California, 90095, United States

Location

University of California Davis Health System

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Children's Hospital, Orlando

Orlando, Florida, 32827, United States

Location

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

Chicago, Illinois, 60611-2605, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Columbia University

New York, New York, 10032, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98101, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 165, Italy

Location

Fondazione Serena Onlus - Centro Clinico Nemo

Milan, 20162, Italy

Location

Hamad General Hospital

Doha, 3050, Qatar

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Hacettepe University Medical Faculty

Ankara, 6230, Turkey (Türkiye)

Location

Yeditepe University Medical School Hospital

Istanbul, 31755, Turkey (Türkiye)

Location

Related Publications (2)

• Crawford TO, Swoboda KJ, De Vivo DC, Bertini E, Hwu WL, Finkel RS, Kirschner J, Kuntz NL, Nazario AN, Parsons JA, Pechmann A, Ryan MM, Butterfield RJ, Topaloglu H, Ben-Omran T, Sansone VA, Jong YJ, Shu F, Zhu C, Raynaud S, Lago TR, Paradis AD, Foster R, Chin R, Berger Z; NURTURE Study Group. Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study. Muscle Nerve. 2023 Aug;68(2):157-170. doi: 10.1002/mus.27853. Epub 2023 Jul 6.

  PMID: 37409780 DERIVED

• 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.

  PMID: 27939059 DERIVED

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 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 12, 2015
• Study Start: May 18, 2015
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: October 20, 2025
• Results First Posted: October 20, 2025

Record last verified: 2025-10

Locations

DE (1); US (11); TW (2); QA (1); TU (2); IT (2); AU (2)