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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

April 22, 2013
March 30, 2017
May 2013
May 2017   (Final data collection date for primary outcome measure)
Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) [ Time Frame: Up to 45 months ]
The number of participants with adverse events [ Time Frame: Patricipants will be followed for the duration of the study; an expected 52 weeks ]
Complete list of historical versions of study NCT01839656 on ClinicalTrials.gov Archive Site
  • 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 ]
Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4 and 24 hours after dosing ]
  • the maximal observed plasma drug concentration (Cmax)
  • the time to reach Cmax in plasma (Tmax)
  • the area under the plasma concentrations time curve from the time of the intrathecal dose to the last collected sample (20 hours after dosing)
Not Provided
CSF Pharmacokinetics (See clarification.) [ Time Frame: CSF at Day 1, Day 15, and Day 85 ]
- The observed CSF drug concentration
 
A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
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
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.

This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..

In August 2016, sponsorship of the trial was transferred to Biogen.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Spinal Muscular Atrophy
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
  • Experimental: Cohort 1 (n=4)
    Intervention: Drug: nusinersen
  • Experimental: Cohort 2 (n=4-16)
    Intervention: Drug: nusinersen
Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, Yamashita M, Rigo F, Hung G, Schneider E, Norris DA, Xia S, Bennett CF, Bishop KM. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017-3026. doi: 10.1016/S0140-6736(16)31408-8. Epub 2016 Dec 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
June 2017
May 2017   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
up to 210 Days   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
 
NCT01839656
ISIS 396443-CS3A
2017-000621-12 ( EudraCT Number )
Yes
Not Provided
Not Provided
Not Provided
Biogen
Biogen
Not Provided
Study Director: Medical Director Biogen
Biogen
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP