An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1 (NCT01494701)

Spinal Muscular Atrophy Clinical Trial

Official title:

An Open-label Study to Assess the Safety and Tolerability of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780246
• Other study ID #: ISIS 396443-CS10
• Status: Completed
• Phase: Phase 1
• Start date: January 31, 2013
• Est. completion date: February 28, 2014

Study information

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

Clinical Trial Summary

The primary objective of this study is to examine the safety and tolerability of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA) who previously participated in ISIS 396443-CS1 (NCT02865109). The secondary objective was to examine the plasma pharmacokinetics of a single dose of ISIS 396443 administered intrathecally to participants with SMA who previously participated in ISIS 396443-CS1.

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: 18
• Est. completion date: February 28, 2014
• Est. primary completion date: February 28, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 15 Years

Eligibility

Key Inclusion Criteria:

• Clinical signs attributable to Spinal Muscular Atrophy

• Satisfactory completion of dosing and all study visits in ISIS 396443-CS1 (NCT01494701) with an acceptable safety profile, per Investigator judgement.

• 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:

• Have any new or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study.

• Dosing in ISIS 396443-CS1 (NCT01494701) within 270 days (9 months) of screening, or longer ago than 450 days (15 months)

• Dosing in ISIS 396443-CS2 (NCT01703988)

• Hospitalization for surgery (i.e. scoliosis surgery) or pulmonary event within 2 months of screening or planned during the duration of the study

• Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy any time during the screening period

• Clinically significant abnormalities in hematology or clinical chemistry parameters

• Treatment with investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Treatment with valproate or hydroxyurea within 1 months of screening. Any history of gene therapy or cell transplantation

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	Boston Children's Hospital	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 24 Weeks
Primary	Number of participants with clinically significant neurological examination abnormalities		Up tp 24 Weeks
Primary	Number of participants with clinically significant vital sign abnormalities		Up to 24 Weeks
Primary	Number of participants with clinically significant physical examination abnormalities		Up to 24 Weeks
Primary	Number of participants with clinically significant weight abnormalities		Up to 24 Weeks
Primary	Number of participants with clinically significant laboratory parameters		Up to 24 Weeks
Primary	Number of participants with clinically significant electrocardiograms (ECGs) abnormalities		Up to 24 Weeks
Primary	Number of participants who use concomitant medications		Up to 24 Weeks
Secondary	PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)		Plasma at 1, 2, 4 and 6 hours after dosing
Secondary	PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)		Plasma at 1, 2, 4 and 6 hours after dosing
Secondary	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 6 hours after dosing
Secondary	PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible		Plasma at 1, 2, 4 and 6 hours after dosing

External Links

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