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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)

Primary Purpose

Spinal Muscular Atrophy

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

nusinersen

About this trial

This is an interventional treatment trial for Spinal Muscular Atrophy focused on measuring Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443

Eligibility Criteria

2 Years - 15 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Boston Children's Hospital
Columbia University Medical Center
UT Southwestern Medical Center - Children's Medical Center Dallas
University of Utah School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

nusinersen

Arm Description

Outcomes

Primary Outcome Measures

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

Number of participants with clinically significant neurological examination abnormalities

Number of participants with clinically significant vital sign abnormalities

Number of participants with clinically significant physical examination abnormalities

Number of participants with clinically significant weight abnormalities

Number of participants with clinically significant laboratory parameters

Number of participants with clinically significant electrocardiograms (ECGs) abnormalities

Number of participants who use concomitant medications

Secondary Outcome Measures

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

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

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)

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

Full Information

NCT ID

NCT01780246

First Posted

January 28, 2013

Last Updated

February 12, 2021

Sponsor

Biogen

1. Study Identification

Unique Protocol Identification Number

NCT01780246

Brief Title

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)

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

January 31, 2013 (Actual)

Primary Completion Date

February 28, 2014 (Actual)

Study Completion Date

February 28, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biogen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

nusinersen

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

nusinersen

Other Intervention Name(s)

Sprinraza, ISIS 396443, IONIS-SMN Rx, BIIB058

Intervention Description

Administered by intrathecal (IT) injection

Primary Outcome Measure Information:

Title

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

Time Frame

Up to 24 Weeks

Title

Number of participants with clinically significant neurological examination abnormalities

Time Frame

Up tp 24 Weeks

Title

Number of participants with clinically significant vital sign abnormalities

Time Frame

Up to 24 Weeks

Title

Number of participants with clinically significant physical examination abnormalities

Time Frame

Up to 24 Weeks

Title

Number of participants with clinically significant weight abnormalities

Time Frame

Up to 24 Weeks

Title

Number of participants with clinically significant laboratory parameters

Time Frame

Up to 24 Weeks

Title

Number of participants with clinically significant electrocardiograms (ECGs) abnormalities

Time Frame

Up to 24 Weeks

Title

Number of participants who use concomitant medications

Time Frame

Up to 24 Weeks

Secondary Outcome Measure Information:

Title

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

Time Frame

Plasma at 1, 2, 4 and 6 hours after dosing

Title

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

Time Frame

Plasma at 1, 2, 4 and 6 hours after dosing

Title

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 6 hours after dosing

Title

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

Time Frame

Plasma at 1, 2, 4 and 6 hours after dosing

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

Boston Children's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

UT Southwestern Medical Center - Children's Medical Center Dallas

City

Dallas

State/Province

Texas

ZIP/Postal Code

75207

Country

United States

Facility Name

University of Utah School of Medicine

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31420846

Citation

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.

Results Reference

derived

PubMed Identifier

26823478

Citation

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.

Results Reference

derived

Links:

URL

http://www.curesma.org

Description

Cure SMA

URL

http://mda.org/disease/spinal-muscular-atrophy

Description

Muscular Dystrophy Association

URL

http://www.rarediseases.org

Description

National Organization for Rare Diseases

URL

http://clinicalresearch.biogen.com/Content/Studies/CS10%20Biogen.com%20Packet.pdf

Description

Clinical Study Report (CSR) Synopsis - a results summary

Learn more about this trial

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)

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