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Spinal Muscular AtrophyPhase 1NCT02052791

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)

A Phase 1 study testing nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246). Read more about this study

Who is it for?
Any age
Conditions the study is for
Spinal Muscular Atrophy
What is being tested?
nusinersen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
4 sitesUnited States
Study dates
31 Jan 2014to 31 Jan 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • UT Southwestern Medical Center - Children's Medical Center Dallas

    Dallas, Texas, 75207

  • Columbia University Medical Center

    New York, New York, 10032

  • University of Utah School of Medicine

    Salt Lake City, Utah, 84132

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
nusinersen
Keywords
Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443, IONIS-SMNRx, IONIS-SMN Rx, Spinraza
Medical subject headings
Muscular Atrophy, Spinal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nusinersenDrug

    Also called ISIS 396443, Spinraza, BIIB058, IONIS SMN Rx

    Administered by intrathecal (IT) injection

Study groups in NCT02052791
Study groupRoleWhat they receive
nusinersenExperimentalNot described
Receives: Drug: nusinersen

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 24 Months

  2. Number of participants with clinically significant neurological examination abnormalities

    Measured: Up to 24 Months

  3. Number of participants with clinically significant vital sign abnormalities

    Measured: Up to 24 Months

  4. Number of participants with clinically significant physical examination abnormalities

    Measured: Up to 24 Months

  5. Number of participants with clinically significant weight abnormalities

    Measured: Up to 24 Months

  6. Number of participants with clinically significant laboratory parameters

    Measured: Up to 24 Months

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

    Measured: Up to Day 176

  8. Number of participants with clinically significant electrocardiograms (ECGs) abnormalities

    Measured: Up to 24 Months

  9. Change from Baseline in concomitant medications

    Measured: Up to 24 Months

Secondary outcomes (3)

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

    Measured: Pre-dose Day 176, Day 358 and Day 540

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

    Measured: Pre-Dose Day 176, Day 358 and Day 540

  3. 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)

    Measured: Pre-Dose Day 176, Day 358 and Day 540

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2014 (estimated)
  2. Study start31 Jan 2014
  3. Primary completion31 Jan 2017
  4. Study completion31 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02052791
Sponsor's protocol ID
ISIS 396443-CS12
Status last verified
Feb 2021
First submitted
30 Jan 2014
Last updated
16 Feb 2021
Results posted
No
Data monitoring committee
Yes
Expanded access
Available

Publications

  • 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.

    PubMed 31420846

  • 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.

    PubMed 31019106

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (time frame: Up to 24 Months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02052791, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2021.

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