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Trial record 1 of 2 for:    NCT01839656
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A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01839656
First received: April 22, 2013
Last updated: March 30, 2017
Last verified: March 2017
  Purpose
The primary objective is to examine the clinical efficacy of multiple doses of nusinersen (ISIS 396443) administered intrathecally to participants with Infantile-Onset Spinal Muscular Atrophy (SMA). The secondary objectives are to examine the safety and tolerability of multiple doses of nusinersen administered intrathecally to participants with infantile-onset SMA and to examine the cerebral spinal fluid (CSF) and plasma Pharmacokinetics (PK) of multiple doses of nusinersen administered intrathecally to participants with infantile-onset SMA.

Condition Intervention Phase
Spinal Muscular Atrophy
Drug: nusinersen
Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Infantile-Onset Spinal Muscular Atrophy

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) [ Time Frame: Up to 45 months ]

Secondary Outcome Measures:
  • Time to death or respiratory intervention [ Time Frame: Up to 45 months ]
  • Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale [ Time Frame: Up to 42 months ]
    CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.

  • Change from Baseline in Compound Muscular Action Potential (CMAP) [ Time Frame: Up to 45 months ]
    CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles

  • Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs) [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant physical examination abnormalities [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant weight abnormalities [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant laboratory parameters [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant cerebrospinal fluid (CSF) laboratory parameters [ Time Frame: Up to 45 months ]
  • Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [ Time Frame: Up to 45 months ]
  • Change from Baseline in concomitant medications [ Time Frame: Up to 45 months ]
  • PK parameters of nusinersen (ISIS 396443) in CSF levels: Maximum observed plasma drug concentration (Cmax) [ Time Frame: Up to 42 months ]
  • PK parameters of nusinersen in CSF levels: Time to reach maximum observed concentration (Tmax) [ Time Frame: Up to 42 months ]
  • PK parameters of nusinersen in CSF levels: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf) [ Time Frame: Up to 42 months ]
  • PK parameters of nusinersen in CSF levels: Apparent terminal elimination half-life (t1/2) [ Time Frame: Up to 42 months ]
  • PK parameters of nusinersen in plasma: (Cmax) [ Time Frame: Up to 45 months ]
  • PK parameters of nusinersen in plasma: (Tmax) [ Time Frame: Up to 45 months ]
  • PK parameters of nusinersen in plasma: (AUCinf) [ Time Frame: Up to 45 months ]
  • PK parameters of nusinersen in plasma: (t1/2) [ Time Frame: Up to 45 months ]

Enrollment: 20
Study Start Date: May 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (n=4) Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
Experimental: Cohort 2 (n=4-16) Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx

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.

  Eligibility

Ages Eligible for Study:   up to 210 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Genetic documentation of 5q SMA (homozygous gene deletion or mutation)
  • Onset of clinical signs and symptoms consistent with SMA at ≥ 21 days and <6 months (180 days) of age
  • At study entry, receiving adequate nutrition and hydration (with or without gastrostomy), in the opinion of the Site Investigator
  • Body weight >5th percentile for age using Center of Disease Control and Prevention (CDC) guidelines
  • Medical care meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA (Wang et al. 2007), in the opinion of the Site Investigator
  • Gestational age of 35 to 42 weeks and gestation body weight ≥2 kg
  • Reside within approximately 9 hours ground-travel distance from a participating study center for the duration of the study. Residence >2 hours ground-travel distance from a study center must obtain clearance from the Site Investigator and the study Medical Monitor
  • Able to complete all study procedures, measurements and visits and parent or guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the Site Investigator

Key Exclusion Criteria:

  • Hypoxemia (O2 saturation awake <96% or O2 saturation asleep <96%, without ventilation support)
  • 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 the lumbar puncture (LP) procedures, CSF circulation, or safety assessments
  • Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
  • History of bacterial meningitis
  • Clinically significant abnormalities in hematology or clinical chemistry parameters, as assessed by the Site Investigator, at screening that would render the participant unsuitable for inclusion
  • Treatment with another investigational drug (e.g., albuterol, riluzole, carnitine, creatine, sodium phenylbutyrate, salbutamol, valproate, hydroxyurea etc), biological agent, or device within 90 days prior to enrollment or anytime during the study. Any history of gene therapy or cell transplantation
  • The participants parent(s) or legal guardian(s) is unable to understand the nature, scope, and possible consequences of the study, or does not agree to comply with the protocol defined schedule of assessments
  • Ongoing medical condition that according to the Site Investigator would interfere with the conduct and assessments of the study. Examples are medical disability other than SMA that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01839656

Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Florida
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Canada, Ontario
The Hospital for Sick Children (SickKids)
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01839656     History of Changes
Other Study ID Numbers: ISIS 396443-CS3A
2017-000621-12 ( EudraCT Number )
Study First Received: April 22, 2013
Last Updated: March 30, 2017

Keywords provided by Biogen:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
ISIS 396443
IONIS-SMNRx
Spinraza

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on April 28, 2017