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)

NCT02052791 | Completed Phase 1 DMC

• 1 other identifier: ISIS 396443-CS12
• Study Type: interventional
• Target: 47
• 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-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.

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy; SMA; SMN; SMNRx; ISIS-SMNRx; ISIS 396443; IONIS-SMNRx; IONIS-SMN Rx; Spinraza

Outcome Measures

Primary Outcomes (9)

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

  Up to 24 Months

• Number of participants with clinically significant neurological examination abnormalities

  Up to 24 Months

• Number of participants with clinically significant vital sign abnormalities

  Up to 24 Months

• Number of participants with clinically significant physical examination abnormalities

  Up to 24 Months

• Number of participants with clinically significant weight abnormalities

  Up to 24 Months

• Number of participants with clinically significant laboratory parameters

  Up to 24 Months

• Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters

  Up to Day 176

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

  Up to 24 Months

• Change from Baseline in concomitant medications

  Up to 24 Months

Secondary Outcomes (3)

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

  Pre-dose Day 176, Day 358 and Day 540

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

  Pre-Dose Day 176, Day 358 and Day 540

• 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)

  Pre-Dose Day 176, Day 358 and Day 540

Study Arms (1)

nusinersen

EXPERIMENTAL

Drug: nusinersen

Interventions

nusinersen DRUG

Administered by intrathecal (IT) injection

Also known as: ISIS 396443, Spinraza, BIIB058, IONIS SMN Rx, ISIS SMNRx

nusinersen

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

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

• 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.

  PMID: 31019106 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 Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

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 30, 2014
• First Posted: February 3, 2014
• Study Start: January 31, 2014
• Primary Completion: January 31, 2017
• Study Completion: January 31, 2017
• Last Updated: February 16, 2021

Record last verified: 2021-02

Locations

US (4)