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.
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-CS1 (NCT02865109). Read more about this study
- 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
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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
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 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 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.
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.
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.
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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.