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)

NCT01780246 | Completed Phase 1 DMC

• 1 other identifier: ISIS 396443-CS10
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

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.

Conditions

Spinal Muscular Atrophy

Keywords

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

Outcome Measures

Primary Outcomes (8)

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

  Up to 24 Weeks

• Number of participants with clinically significant neurological examination abnormalities

  Up tp 24 Weeks

• Number of participants with clinically significant vital sign abnormalities

  Up to 24 Weeks

• Number of participants with clinically significant physical examination abnormalities

  Up to 24 Weeks

• Number of participants with clinically significant weight abnormalities

  Up to 24 Weeks

• Number of participants with clinically significant laboratory parameters

  Up to 24 Weeks

• Number of participants with clinically significant electrocardiograms (ECGs) abnormalities

  Up to 24 Weeks

• Number of participants who use concomitant medications

  Up to 24 Weeks

Secondary Outcomes (4)

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

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

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

  Plasma at 1, 2, 4 and 6 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)

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

• 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

Study Arms (1)

nusinersen

EXPERIMENTAL

Drug: nusinersen

Interventions

nusinersen DRUG

Administered by intrathecal (IT) injection

Also known as: Sprinraza, ISIS 396443, IONIS-SMN Rx, BIIB058

nusinersen

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (4)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UT Southwestern Medical Center - Children's Medical Center Dallas

Dallas, Texas, 75207, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• 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.

  PMID: 31420846 DERIVED

• 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.

  PMID: 26823478 DERIVED

Related Links

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

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

nusinersen

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 28, 2013
• First Posted: January 31, 2013
• Study Start: January 31, 2013
• Primary Completion: February 28, 2014
• Study Completion: February 28, 2014
• Last Updated: February 16, 2021

Record last verified: 2021-02

Locations

US (4)