Spinal Muscular AtrophyPhase 1NCT01780246

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)

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

Who is it for?: Ages 2 to 15 years
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: 18 participants
Where: 4 sitesUnited States
Study dates: 31 Jan 2013to 28 Feb 2014
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 2 to 15 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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.

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 a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1

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.

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.

Conditions: Spinal Muscular Atrophy
Being tested: nusinersen
Keywords: Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443
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 Sprinraza, ISIS 396443, IONIS-SMN Rx, BIIB058
Administered by intrathecal (IT) injection

Study groups in NCT01780246
Study group	Role	What they receive
nusinersen	Experimental	Not described Receives: Drug: nusinersen

What is being measured

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

Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Measured: Up to 24 Weeks
Number of participants with clinically significant neurological examination abnormalities
Measured: Up tp 24 Weeks
Number of participants with clinically significant vital sign abnormalities
Measured: Up to 24 Weeks
Number of participants with clinically significant physical examination abnormalities
Measured: Up to 24 Weeks
Number of participants with clinically significant weight abnormalities
Measured: Up to 24 Weeks
Number of participants with clinically significant laboratory parameters
Measured: Up to 24 Weeks
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Measured: Up to 24 Weeks
Number of participants who use concomitant medications
Measured: Up to 24 Weeks

Secondary outcomes (4)

PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
Measured: Plasma at 1, 2, 4 and 6 hours after dosing
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
Measured: 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)
Measured: 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
Measured: Plasma at 1, 2, 4 and 6 hours after dosing

Timeline

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

31 Jan 201328 Feb 2014

First posted31 Jan 2013 (estimated)
Study start31 Jan 2013
Primary completion28 Feb 2014
Study completion28 Feb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01780246
Sponsor's protocol ID: ISIS 396443-CS10
Status last verified: Feb 2021
First submitted: 28 Jan 2013
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
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.
PubMed 26823478

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Spinal Muscular Atrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01780246
Acronym / sponsor ID: ISIS 396443-CS10
Conditions: Spinal Muscular Atrophy
Keywords: Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: 31 Jan 2013 (actual)
Primary completion: 28 Feb 2014 (actual)
Study completion: 28 Feb 2014 (actual)
First posted: 31 Jan 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
nusinersen	Experimental	Drug: nusinersen

Who may qualify

Ages: 2 to 15 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

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 (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
nusinersenAlso: Sprinraza, ISIS 396443, IONIS-SMN Rx, BIIB058Administered by intrathecal (IT) injection	Drug	nusinersen

Primary outcome

Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Time frame: Up to 24 Weeks
Number of participants with clinically significant neurological examination abnormalities
Time frame: Up tp 24 Weeks
Number of participants with clinically significant vital sign abnormalities
Time frame: Up to 24 Weeks
Number of participants with clinically significant physical examination abnormalities
Time frame: Up to 24 Weeks
Number of participants with clinically significant weight abnormalities
Time frame: Up to 24 Weeks
Number of participants with clinically significant laboratory parameters
Time frame: Up to 24 Weeks
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Time frame: Up to 24 Weeks
Number of participants who use concomitant medications
Time frame: Up to 24 Weeks

4 secondary outcomes

PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
Time frame: Plasma at 1, 2, 4 and 6 hours after dosing
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
Time frame: 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)
Time frame: 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
Time frame: Plasma at 1, 2, 4 and 6 hours after dosing

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2021.
Derived from this study: PubMed 31420846Darras 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.
Derived from this study: PubMed 26823478Hache 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.
Cure SMALink provided by the sponsor.
Muscular Dystrophy AssociationLink provided by the sponsor.
National Organization for Rare DiseasesLink provided by the sponsor.
Clinical Study Report (CSR) Synopsis - a results summaryLink provided by the sponsor.

Related trials for Spinal Muscular Atrophy

Active, not recruitingPhase 4
A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy
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Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
A Study of Risdiplam in Participants With Type I and Type II Spinal Muscle Atrophy (SMA)
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A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1)
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Assessment of a Portable Digital Device for Quantified Analysis of Markerless Walking in Volunteers With Neuromuscular Diseases or Asymptomatic Volunteers
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 1 country: see every site and its status.

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 8 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 Weeks). The study lists 8 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 NCT01780246, 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.