An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)

• Register: ClinicalTrials.gov
• Last refreshed on: 1 March 2021
• Main ID: NCT01494701
• Date of registration: 13/12/2011
• Prospective Registration: No
• Primary sponsor: Biogen
• Public title: An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) SMNRx
• Scientific 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
• Date of first enrolment: November 30, 2011
• Target sample size: 28
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01494701
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- 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:

- 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

- 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.



Age minimum: 2 Years
Age maximum: 14 Years
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Drug: nusinersen

Primary Outcome(s)

Number of participants that experience Adverse Events (AEs) and Serious Adverse Events [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 weight abnormalities [Time Frame: Up to 88 Days]

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]

Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [Time Frame: Up to 88 Days]

Number of participants with clinically significant laboratory parameters [Time Frame: Up to 88 Days]

Number of participants with clinically significant physical examination abnormalities [Time Frame: Up to 88 Days]

Number of participants who use concomitant medications [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]

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]

PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax) [Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing]

Secondary ID(s)

ISIS 396443 - CS1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors