search
Back to results

An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246)

Primary Purpose

Spinal Muscular Atrophy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
nusinersen
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

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, IONIS-SMNRx, IONIS-SMN Rx, Spinraza

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)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-CS2 (NCT01703988) or ISIS 396443 CS10 (NCT01780246) 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 subject unsuitable for enrollment, or could interfere with the participant participating in or completing the study.
  • Dosing in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246) within 180 days (6 months) of screening, or longer ago than 396 days (13 months) from screening
  • 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
  • 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.

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 or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Change from Baseline in concomitant medications

Secondary Outcome Measures

PK parameters of nusinersen (ISIS 396443) in CSF levels: Maximum observed plasma drug concentration (Cmax)
PK parameters of nusinersen in CSF levels: Time to reach maximum observed concentration (Tmax)
PK parameters of nusinersen in CSF levels: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf)

Full Information

First Posted
January 30, 2014
Last Updated
February 12, 2021
Sponsor
Biogen
search

1. Study Identification

Unique Protocol Identification Number
NCT02052791
Brief Title
An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246)
Official Title
An Open-label Study to Assess the Safety and Tolerability of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated in 396443-CS2 or 396443-CS10
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
January 31, 2014 (Actual)
Primary Completion Date
January 31, 2017 (Actual)
Study Completion Date
January 31, 2017 (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-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246). The secondary objective is to examine the plasma and cerebrospinal fluid (CSF) pharmacokinetic(s) (PK) of nusinersen administered intrathecally to participants with SMA who previously participated in ISIS 396443-CS2 or ISIS 396443-CS10.
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, IONIS-SMNRx, IONIS-SMN Rx, Spinraza

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
nusinersen
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
nusinersen
Other Intervention Name(s)
ISIS 396443, Spinraza, BIIB058, IONIS SMN Rx, ISIS SMNRx
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 Months
Title
Number of participants with clinically significant neurological examination abnormalities
Time Frame
Up to 24 Months
Title
Number of participants with clinically significant vital sign abnormalities
Time Frame
Up to 24 Months
Title
Number of participants with clinically significant physical examination abnormalities
Time Frame
Up to 24 Months
Title
Number of participants with clinically significant weight abnormalities
Time Frame
Up to 24 Months
Title
Number of participants with clinically significant laboratory parameters
Time Frame
Up to 24 Months
Title
Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
Time Frame
Up to Day 176
Title
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Time Frame
Up to 24 Months
Title
Change from Baseline in concomitant medications
Time Frame
Up to 24 Months
Secondary Outcome Measure Information:
Title
PK parameters of nusinersen (ISIS 396443) in CSF levels: Maximum observed plasma drug concentration (Cmax)
Time Frame
Pre-dose Day 176, Day 358 and Day 540
Title
PK parameters of nusinersen in CSF levels: Time to reach maximum observed concentration (Tmax)
Time Frame
Pre-Dose Day 176, Day 358 and Day 540
Title
PK parameters of nusinersen in CSF levels: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf)
Time Frame
Pre-Dose Day 176, Day 358 and Day 540

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Clinical signs attributable to Spinal Muscular Atrophy Satisfactory completion of dosing and all study visits in ISIS 396443-CS2 (NCT01703988) or ISIS 396443 CS10 (NCT01780246) 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 subject unsuitable for enrollment, or could interfere with the participant participating in or completing the study. Dosing in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246) within 180 days (6 months) of screening, or longer ago than 396 days (13 months) from screening 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 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. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
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
31019106
Citation
Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, Xia S, Bennett CF, Bishop KM, Shefner JM, Green AM, Sun P, Bhan I, Gheuens S, Schneider E, Farwell W, De Vivo DC; ISIS-396443-CS2/ISIS-396443-CS12 Study Groups. Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies. Neurology. 2019 May 21;92(21):e2492-e2506. doi: 10.1212/WNL.0000000000007527. Epub 2019 Apr 24.
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
https://www.rarediseases.org
Description
National Organization for Rare Diseases
URL
http://clinicalresearch.biogen.com/Content/Studies/CS12%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 (SMA) Who Previously Participated in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246)

We'll reach out to this number within 24 hrs