A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy

NCT ID: NCT02193074

Last Updated: 2021-02-17

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-19

Study Completion Date

2016-11-21

Brief Summary

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The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset with infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.

Detailed Description

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This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..

In August 2016, sponsorship of the trial was transferred to Biogen.

Conditions

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Spinal Muscular Atrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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nusinersen

Group Type EXPERIMENTAL

nusinersen

Intervention Type DRUG

Administered by intrathecal (IT) injection as specified in the treatment arm.

Sham procedure

Group Type SHAM_COMPARATOR

Sham procedure

Intervention Type PROCEDURE

Small needle prick on the lower back at the location where the IT injection is normally made

Interventions

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nusinersen

Administered by intrathecal (IT) injection as specified in the treatment arm.

Intervention Type DRUG

Sham procedure

Small needle prick on the lower back at the location where the IT injection is normally made

Intervention Type PROCEDURE

Other Intervention Names

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ISIS 396443 BIIB058 Spinraza IONIS-SMN Rx ISIS SMNRx

Eligibility Criteria

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Inclusion Criteria

* Be born (gestational age) between 37 and 42 weeks
* Be medically diagnosed with spinal muscular atrophy (SMA)
* Have Survival Motor Neuron2 (SMN2) Copy number = 2
* Body weight equal to or greater than 3rd percentile for age using appropriate country-specific guidelines
* Be able to follow all study procedures
* Reside within approximately 9 hours ground-travel distance from a participating study center, for the duration of the study

Exclusion Criteria

* Hypoxemia (oxygen \[O2\] saturation awake less than 96% or O2 saturation asleep less than 96%, without ventilation support) during screening evaluation
* Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
* Participant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
Maximum Eligible Age

210 Days

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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UCLA Medical Center

Los Angeles, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Duke Children's Hospital

Durham, North Carolina, United States

Site Status

Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia - Neurology

Philadelphia, Pennsylvania, United States

Site Status

UT Southwestern Medical Center/Children's Medical Center Dallas

Dallas, Texas, United States

Site Status

Primary Children's Medical Center (University of Utah)

Salt Lake City, Utah, United States

Site Status

Sydney Children's Hospital

Sydney, New South Wales, Australia

Site Status

Royal Children's Hospital, Children's Neuroscience Centre

Parkville, Victoria, Australia

Site Status

Hôpital Universitaire des Enfants Reine FABIOLA (HUDERF)

Brussels, , Belgium

Site Status

British Columbia Children's Hospital/UBC

Vancouver, British Columbia, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Institut de Myologie

Paris, , France

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

Universtatsklinikum Freiburg, Zentrum fur Kinder-und Jugendmedizin , Abteilung Neuropadiatrie und Muskelerkrankungen

Freiburg im Breisgau, , Germany

Site Status

Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative

Genova, , Italy

Site Status

Pediatric Neurology Unit, Catholic University

Rome, , Italy

Site Status

Hyogo College of Medicine

Nishinomiya, Hyōgo, Japan

Site Status

Tokyo Women's Medical University

Tokyo, , Japan

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario La Paz, Pediatric Neurology Department

Madrid, , Spain

Site Status

University of Gothenburg, The Queen Silvia Children's Hospital

Gothenburg, , Sweden

Site Status

Hacettepe Children's Hospital

Ankara, , Turkey (Türkiye)

Site Status

UCL Institute of Child Health/Great Ormond Street

London, , United Kingdom

Site Status

MRC Centre for Neuromuscular Diseases at Newcastle, Institute of Genetic Medicine Newcastle University

Newcastle, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Italy Japan South Korea Spain Sweden Turkey (Türkiye) United Kingdom

References

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Darras BT, Farrar MA, Mercuri E, Finkel RS, Foster R, Hughes SG, Bhan I, Farwell W, Gheuens S. An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials. CNS Drugs. 2019 Sep;33(9):919-932. doi: 10.1007/s40263-019-00656-w.

Reference Type DERIVED
PMID: 31420846 (View on PubMed)

Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guerin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM. Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1. Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.

Reference Type DERIVED
PMID: 30879249 (View on PubMed)

Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.

Reference Type DERIVED
PMID: 29091570 (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)

Related Links

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https://www.rarediseases.org

National Organization for Rare Diseases

http://clinicalresearch.biogen.com/Content/Studies/CS3b%20Biogen.com%20Packet.pdf

Clinical Study Report (CSR) Synopsis - a results summary

Other Identifiers

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2013-004422-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 396443-CS3B

Identifier Type: -

Identifier Source: org_study_id

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