An Open-label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01703988 |
Recruitment Status :
Completed
First Posted : October 11, 2012
Results First Posted : March 13, 2017
Last Update Posted : April 13, 2021
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
This study will test the safety, tolerability, and pharmacokinetics of escalating doses of nusinersen (ISIS 396443) administered into the spinal fluid either two or three times over the duration of the trial, in participants with spinal muscular atrophy (SMA).
Four dose levels will be evaluated sequentially. Each dose level will be studied in a cohort of approximately 8 participants, where all participants will receive active drug.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Spinal Muscular Atrophy | Drug: Nusinersen | Phase 1 Phase 2 |
Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial. More info ...
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 34 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | An Open-Label, Dose Escalation Study to Assess the Safety, Tolerability and Dose-Range Finding of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Spinal Muscular Atrophy |
Actual Study Start Date : | October 31, 2012 |
Actual Primary Completion Date : | January 31, 2015 |
Actual Study Completion Date : | January 31, 2015 |

Arm | Intervention/treatment |
---|---|
Experimental: Nusinersen 3 mg
3 mg nusinersen on Days 1, 29, 85, intrathecal (IT) injection
|
Drug: Nusinersen
Single IT injection for each dose
Other Names:
|
Experimental: Nusinersen 6 mg
6 mg nusinersen on Days 1, 29, 85, IT injection
|
Drug: Nusinersen
Single IT injection for each dose
Other Names:
|
Experimental: Nusinersen 9 mg
9 mg nusinersen on Days 1 and 85, IT injection
|
Drug: Nusinersen
Single IT injection for each dose
Other Names:
|
Experimental: Nusinersen 12 mg
12 mg nusinersen on Days 1, 29, 85, IT injection
|
Drug: Nusinersen
Single IT injection for each dose
Other Names:
|
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuations Due to AEs, and Highest Severity of AEs [ Time Frame: Participants were followed for the duration of the study; mean (SD) duration of treatment was 82.9 (15.4) days ]An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of the investigational drug product, whether or not the AE is considered related to the investigational drug product. An SAE is any AE that, in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; and is an important medical event in the judgment of the investigator. Drug-related is an event related or possibly related to study drug. Severity of AEs was assessed as mild, moderate, or severe.
- Plasma Pharmacokinetics: Maximal Observed Plasma Drug Concentration (Cmax) [ Time Frame: Day 1 and Day 85 ]
- Plasma Pharmacokinetics: Time to Reach Cmax in Plasma [ Time Frame: Day 1 and Day 85 ]
- Plasma Pharmacokinetics: Plasma Pharmacokinetics: Area Under the Plasma Concentration Time Curve From the Time of the IT Dose to 6 Hours After Dosing (AUC0-6hr) [ Time Frame: Day 1 and Day 85 ]
- Cerebrospinal Fluid (CSF) Pharmacokinetics: Predose CSF Drug Concentrations [ Time Frame: Day 1, Day 29, and Day 85 ]
- Urine Pharmacokinetics: Renal Clearance, Cohort 4 [ Time Frame: Day 1 and Day 85 ]Renal clearance of nusinersen for participants was assessed in the 12 mg reporting group only, per protocol.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 2 Years to 15 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Genetic documentation of 5q SMA (homozygous gene deletion or mutation)
- Clinical signs attributable to SMA
- Able to complete all study procedures, measurements, and visits and parent/patient 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:
- Respiratory insufficiency defined by the medical necessity for invasive or non-invasive ventilation during a 24-hour period
- Medical necessity for a gastric feeding tube, where the majority of feeds are given by this route, as assessed by the Investigator
- Previous scoliosis surgery that would interfere with the lumbar puncture injection procedure
- Hospitalization for surgery (e.g. 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 at any time during the screening period
- History of brain or spinal cord disease that would interfere with lumbar puncture procedures or cerebrospinal fluid (CSF) circulation
- Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system catheter
- History of bacterial meningitis
- Dosing with ISIS 396443 in clinical study ISIS 396443-CS1 Cohorts 2, 3, or 4
- Dosing with ISIS 396443 in clinical study ISIS 396443-CS10
- Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG) at the Screening visit, as assessed by the Site Investigator that would render the subject unsuitable for inclusion
- 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 3-months of screening. 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) that would interfere with the assessment of safety or would compromise the ability of the patient to undergo study procedures.
NOTE: Other protocol defined inclusion/exclusion criteria may apply.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01703988
United States, Massachusetts | |
Boston Children's Hospital | |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
Columbia University Medical Center | |
New York, New York, United States, 10032 | |
United States, Texas | |
UT Southwestern Medical Center - Children's Medical Center Dallas | |
Dallas, Texas, United States, 75207 | |
United States, Utah | |
University of Utah School of Medicine | |
Salt Lake City, Utah, United States, 84132 |
Study Director: | Medical Director | Biogen |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Biogen |
ClinicalTrials.gov Identifier: | NCT01703988 |
Other Study ID Numbers: |
ISIS 396443 - CS2 2017-000327-27 ( EudraCT Number ) |
First Posted: | October 11, 2012 Key Record Dates |
Results First Posted: | March 13, 2017 |
Last Update Posted: | April 13, 2021 |
Last Verified: | March 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/ |
URL: | https://vivli.org/ |
Spinal Muscular Atrophy SMA SMN |
SMNRx ISIS-SMNRx ISIS 396443 |
Muscular Atrophy Muscular Atrophy, Spinal Atrophy Pathological Conditions, Anatomical Neuromuscular Manifestations Neurologic Manifestations |
Nervous System Diseases Spinal Cord Diseases Central Nervous System Diseases Motor Neuron Disease Neurodegenerative Diseases Neuromuscular Diseases |