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

NCT ID: NCT02386553

Last Updated: 2025-10-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-18

Study Completion Date

2024-12-17

Brief Summary

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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.

Detailed Description

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Conditions

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Spinal Muscular Atrophy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Nusinersen

Nusinersen administered as an intrathecal injection

Group Type EXPERIMENTAL

Nusinersen

Intervention Type DRUG

Solution for intrathecal injection

Interventions

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Nusinersen

Solution for intrathecal injection

Intervention Type DRUG

Other Intervention Names

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ISIS 396443 BIIB058 ISIS SMNRx Spinraza

Eligibility Criteria

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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.

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.
Minimum Eligible Age

0 Weeks

Maximum Eligible Age

6 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

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David Geffen School of Medicine

Los Angeles, California, United States

Site Status

University of California Davis Health System

Sacramento, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Nemours Children's Hospital, Orlando

Orlando, Florida, United States

Site Status

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

Chicago, Illinois, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Columbia University

New York, New York, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Seattle Children's Research Institute

Seattle, Washington, United States

Site Status

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

Site Status

Fondazione Serena Onlus - Centro Clinico Nemo

Milan, , Italy

Site Status

Hamad General Hospital

Doha, , Qatar

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Yeditepe University Medical School Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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United States Australia Germany Italy Qatar Taiwan Turkey (Türkiye)

References

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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.

Reference Type DERIVED
PMID: 37409780 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27939059 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-002098-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

232SM201

Identifier Type: -

Identifier Source: org_study_id

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