Spinal Muscular AtrophyPhase 1SMNRxNCT01494701
An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)
A Phase 1 study testing nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 4 sites in United States.
Trial summary
This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA). Read more about this study
- Who is it for?
- Ages 2 to 14 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
- 28 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Nov 2011to 31 Jan 2013
- 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 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Documented Survival Motor Neuron1 (SMN1) homozygous gene deletion
- Clinical signs attributable to Spinal Muscular Atrophy (SMA)
- 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
- Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
- Presence of a gastric feeding tube
- Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the lumbar puncture (LP) injection procedure
- Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
- History of brain or spinal cord disease that would interfere with LP procedures or cerebrospinal fluid (CSF) circulation
Show all 12Show fewer
- Presence of an implanted shunt for the draining of CSF or an implanted Central Nervous System (CNS) catheter
- History of bacterial meningitis
- 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
- Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the participant to undergo study procedures
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Children's Hospital Boston
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
About this study
Official title: An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy
This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA).
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-SMN Rx, 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, BIIB058, Spinraza, IONIS-SMN Rx
Administered by intrathecal (IT) injection
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (n=6) | Experimental | Not described Receives: Drug: nusinersen |
| Cohort 2 (n=6) | Experimental | Not described Receives: Drug: nusinersen |
| Cohort 3 (n=6) | Experimental | Not described Receives: Drug: nusinersen |
| Cohort 4 (n=10) | 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 88 Days
Number of participants with clinically significant neurological examination abnormalities
Measured: Up to 88 Days
Number of participants with clinically significant vital sign abnormalities
Measured: Up to 88 Days
Number of participants with clinically significant physical examination abnormalities
Measured: Up to 88 Days
Number of participants with clinically significant weight abnormalities
Measured: Up to 88 Days
Number of participants with clinically significant laboratory parameters
Measured: Up to 88 Days
Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
Measured: Up to 88 Days
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Measured: Up to 88 Days
Number of participants who use concomitant medications
Measured: Up to 88 Days
PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
Measured: Plasma at 1, 2, 4 and 20 hours after dosing
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
Measured: Plasma at 1, 2, 4 and 20 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 20 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 20 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2011 (estimated)
- Study start30 Nov 2011
- Primary completion31 Jan 2013
- Study completion31 Jan 2013
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01494701
- Sponsor's protocol ID
- ISIS 396443 - CS1
- Acronym
- SMNRx
- Status last verified
- Feb 2021
- First submitted
- 13 Dec 2011
- Last updated
- 18 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 31420846Hache 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
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT01494701
- Acronym / sponsor ID
- SMNRx / ISIS 396443 - CS1
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS-SMN Rx, ISIS 396443, IONIS-SMNRx
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2011 (actual)
- Primary completion
- 31 Jan 2013 (actual)
- Study completion
- 31 Jan 2013 (actual)
- First posted
- 19 Dec 2011 (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.
This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA).
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (n=6) | Experimental | Drug: nusinersen |
| Cohort 2 (n=6) | Experimental | Drug: nusinersen |
| Cohort 3 (n=6) | Experimental | Drug: nusinersen |
| Cohort 4 (n=10) | Experimental | Drug: nusinersen |
Who may qualify
- Ages
- 2 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Documented Survival Motor Neuron1 (SMN1) homozygous gene deletion
- Clinical signs attributable to Spinal Muscular Atrophy (SMA)
- 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 (12 listed)
- Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
- Presence of a gastric feeding tube
- Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the lumbar puncture (LP) injection procedure
- Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
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: ISIS 396443, BIIB058, Spinraza, IONIS-SMN RxAdministered by intrathecal (IT) injection | Drug | Cohort 1 (n=6), Cohort 2 (n=6), Cohort 3 (n=6), Cohort 4 (n=10) |
Primary outcome
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Time frame: Up to 88 Days
Number of participants with clinically significant neurological examination abnormalities
Time frame: Up to 88 Days
Number of participants with clinically significant vital sign abnormalities
Time frame: Up to 88 Days
Number of participants with clinically significant physical examination abnormalities
Time frame: Up to 88 Days
Number of participants with clinically significant weight abnormalities
Time frame: Up to 88 Days
Number of participants with clinically significant laboratory parameters
Time frame: Up to 88 Days
Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
Time frame: Up to 88 Days
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Time frame: Up to 88 Days
Number of participants who use concomitant medications
Time frame: Up to 88 Days
PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
Time frame: Plasma at 1, 2, 4 and 20 hours after dosing
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
Time frame: Plasma at 1, 2, 4 and 20 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 20 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 20 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 18 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.
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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.
Medical Director study director
Biogen
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 12 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 18 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 88 Days). The study lists 13 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 NCT01494701, 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 18 Feb 2021; AzTrials last refreshed its copy on 29 Oct 2026.