Skip to main content
OpenTrials
Completed

NCT Number: NCT01494701

An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Spinal Muscular Atrophy Central Nervous System Diseases Motor Neuron Disease Muscular Atrophy, Spinal Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Spinal Cord Diseases

Age range

2 year–14 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Children's Hospital Boston, Boston, Massachusetts, United States

Loading trial locations.

About this study

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

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

nusinersen

Drug

Administered by intrathecal (IT) injection

Other names: ISIS 396443, BIIB058, Spinraza, IONIS-SMN Rx, ISIS SMNRx

Primary outcomes

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

    Time frame: Up to 88 Days

  2. Number of participants with clinically significant neurological examination abnormalities

    Time frame: Up to 88 Days

  3. Number of participants with clinically significant vital sign abnormalities

    Time frame: Up to 88 Days

  4. Number of participants with clinically significant physical examination abnormalities

    Time frame: Up to 88 Days

  5. Number of participants with clinically significant weight abnormalities

    Time frame: Up to 88 Days

  6. Number of participants with clinically significant laboratory parameters

    Time frame: Up to 88 Days

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

    Time frame: Up to 88 Days

  8. Number of participants with clinically significant electrocardiograms (ECGs) abnormalities

    Time frame: Up to 88 Days

  9. Number of participants who use concomitant medications

    Time frame: Up to 88 Days

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

    Time frame: Plasma at 1, 2, 4 and 20 hours after dosing

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

    Time frame: Plasma at 1, 2, 4 and 20 hours after dosing

  12. 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)

    Time frame: Plasma at 1, 2, 4 and 20 hours after dosing

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

    Time frame: Plasma at 1, 2, 4 and 20 hours after dosing

Sponsors and collaborators

Lead sponsor

Biogen

Industry

Registry information

Official study title

An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy

Acronym: SMNRx

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Dec 19, 2011
Registry last updated
Feb 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.