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

Spinal Muscular Atrophy Clinical Trial

— SMNRx  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01494701
• Other study ID #: ISIS 396443 - CS1
• Status: Completed
• Phase: Phase 1
• Start date: November 30, 2011
• Est. completion date: January 31, 2013

Study information

• Verified date: February 2021
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: January 31, 2013
• Est. primary completion date: January 31, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 14 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Drug:
• nusinersen
Administered by intrathecal (IT) injection

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts
United States	UT Southwestern Medical Center - Children's Medical Center Dallas	Dallas	Texas
United States	Columbia University Medical Center	New York	New York
United States	University of Utah School of Medicine	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   Clinical Study Report (CSR) Synopsis - a results summary
•   Cure SMA
•   Muscular Dystrophy Association
•   National Organization for Rare Diseases