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

February 17, 2021 updated by: Biogen

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

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

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Texas
      • Dallas, Texas, United States, 75207
        • UT Southwestern Medical Center - Children's Medical Center Dallas
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 14 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 (n=6)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • ISIS SMNRx
  • IONIS-SMN Rx
Experimental: Cohort 2 (n=6)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • ISIS SMNRx
  • IONIS-SMN Rx
Experimental: Cohort 3 (n=6)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • ISIS SMNRx
  • IONIS-SMN Rx
Experimental: Cohort 4 (n=10)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • ISIS SMNRx
  • IONIS-SMN Rx

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants with clinically significant neurological examination abnormalities
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants with clinically significant vital sign abnormalities
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants with clinically significant physical examination abnormalities
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants with clinically significant weight abnormalities
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants with clinically significant laboratory parameters
Time Frame: Up to 88 Days
Up to 88 Days
Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Time Frame: Up to 88 Days
Up to 88 Days
Number of participants who use concomitant medications
Time Frame: Up to 88 Days
Up to 88 Days
PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing
Plasma at 1, 2, 4 and 20 hours after dosing
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing
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)
Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing
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
Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing
Plasma at 1, 2, 4 and 20 hours after dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2011

Primary Completion (Actual)

January 31, 2013

Study Completion (Actual)

January 31, 2013

Study Registration Dates

First Submitted

December 13, 2011

First Submitted That Met QC Criteria

December 15, 2011

First Posted (Estimate)

December 19, 2011

Study Record Updates

Last Update Posted (Actual)

February 18, 2021

Last Update Submitted That Met QC Criteria

February 17, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISIS 396443 - CS1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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