NCT01494701

Brief Summary

This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2011

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 30, 2011

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

December 13, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 19, 2011

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2013

Completed
Last Updated

February 18, 2021

Status Verified

February 1, 2021

Enrollment Period

1.2 years

First QC Date

December 13, 2011

Last Update Submit

February 17, 2021

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular AtrophySMASMNSMNRxISIS-SMNRxISIS-SMN RxISIS 396443IONIS-SMNRxIONIS-SMN RxSpinraza

Outcome Measures

Primary Outcomes (13)

  • Number of participants that experience Adverse Events (AEs) and Serious Adverse Events

    Up to 88 Days

  • Number of participants with clinically significant neurological examination abnormalities

    Up to 88 Days

  • Number of participants with clinically significant vital sign abnormalities

    Up to 88 Days

  • Number of participants with clinically significant physical examination abnormalities

    Up to 88 Days

  • Number of participants with clinically significant weight abnormalities

    Up to 88 Days

  • Number of participants with clinically significant laboratory parameters

    Up to 88 Days

  • Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters

    Up to 88 Days

  • Number of participants with clinically significant electrocardiograms (ECGs) abnormalities

    Up to 88 Days

  • Number of participants who use concomitant medications

    Up to 88 Days

  • PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)

    Plasma at 1, 2, 4 and 20 hours after dosing

  • PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)

    Plasma at 1, 2, 4 and 20 hours after dosing

  • PK parameters of nusinersen: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf)

    Plasma at 1, 2, 4 and 20 hours after dosing

  • PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible

    Plasma at 1, 2, 4 and 20 hours after dosing

Study Arms (4)

Cohort 1 (n=6)

EXPERIMENTAL
Drug: nusinersen

Cohort 2 (n=6)

EXPERIMENTAL
Drug: nusinersen

Cohort 3 (n=6)

EXPERIMENTAL
Drug: nusinersen

Cohort 4 (n=10)

EXPERIMENTAL
Drug: nusinersen

Interventions

nusinersenDRUG

Administered by intrathecal (IT) injection

Also known as: ISIS 396443, BIIB058, Spinraza, IONIS-SMN Rx, ISIS SMNRx
Cohort 1 (n=6)Cohort 2 (n=6)Cohort 3 (n=6)Cohort 4 (n=10)

Eligibility Criteria

Age2 Years - 14 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Documented Survival Motor Neuron1 (SMN1) homozygous gene deletion
  • Clinical signs attributable to Spinal Muscular Atrophy (SMA)
  • Able to complete all study procedures, measurements and visits and parent/participant has adequately supportive psychosocial circumstances, in the opinion of the investigator
  • Estimated life expectancy \> 2 years from Screening
  • Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedure

You may not qualify if:

  • Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
  • Presence of a gastric feeding tube
  • Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the lumbar puncture (LP) injection procedure
  • Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
  • Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
  • History of brain or spinal cord disease that would interfere with LP procedures or cerebrospinal fluid (CSF) circulation
  • Presence of an implanted shunt for the draining of CSF or an implanted Central Nervous System (CNS) catheter
  • History of bacterial meningitis
  • Clinically significant abnormalities in hematology or clinical chemistry parameters
  • Treatment with another investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent whichever is longer. Any history of gene therapy or cell transplantation
  • Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the participant to undergo study procedures

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UT Southwestern Medical Center - Children's Medical Center Dallas

Dallas, Texas, 75207, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

  • 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.

    PMID: 31420846DERIVED

  • Hache M, Swoboda KJ, Sethna N, Farrow-Gillespie A, Khandji A, Xia S, Bishop KM. Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. J Child Neurol. 2016 Jun;31(7):899-906. doi: 10.1177/0883073815627882. Epub 2016 Jan 27.

    PMID: 26823478DERIVED

Related Links

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

nusinersen

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesNeuromuscular Diseases

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

December 13, 2011

First Posted

December 19, 2011

Study Start

November 30, 2011

Primary Completion

January 31, 2013

Study Completion

January 31, 2013

Last Updated

February 18, 2021

Record last verified: 2021-02

Locations

US(4)