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A Study to Assess the Efficacy and Safety of IONIS-SMN Rx in Patients With Later-onset Spinal Muscular Atrophy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02292537
First received: November 12, 2014
Last updated: August 15, 2016
Last verified: August 2016
  Purpose
This study will test the Clinical Efficacy and Safety of IONIS-SMN Rx in patients with later-onset Spinal Muscular Atrophy.

Condition Intervention Phase
Spinal Muscular Atrophy
Drug: IONIS-SMN Rx
Procedure: Sham procedure
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Later-onset Spinal Muscular Atrophy

Resource links provided by NLM:


Further study details as provided by Ionis Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Change from baseline in Hammersmith Functional Motor Scale - Expanded score [ Time Frame: At 15 months ]

Secondary Outcome Measures:
  • Proportion of subjects who achieve a 3-point increase from baseline in Hammersmith Functional Motor Scale - Expanded score [ Time Frame: At 15 months ]
  • Proportion of subject that achieve any new motor milestone [ Time Frame: At 15 months ]
  • Number of motor milestones achieved per subject [ Time Frame: At 15 months ]
  • Change from baseline in Upper Limb Module Test [ Time Frame: At 15 months ]
  • Proportion of subjects that achieve standing alone [ Time Frame: At 15 months ]
  • Proportion of subject that achieve walking with assistance [ Time Frame: At 15 months ]

Estimated Enrollment: 117
Study Start Date: November 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IONIS-SMN Rx
Administered by intrathecal injection
Drug: IONIS-SMN Rx
Administered by intrathecal injection
Other Name: ISIS 396443
Sham Comparator: Sham procedure
Small needle prick on the lower back at the location where the IT injection is normally made
Procedure: Sham procedure
Small needle prick on the lower back at the location where the IT injection is normally made

Detailed Description:
This is a Phase 3 multicenter, double-blind, randomized, sham-procedure controlled study of IONIS-SMN Rx in patients with later-onset SMA. Subjects will be randomized 2:1 to receive IONIS-SMN Rx or a sham procedure control, respectively.
  Eligibility

Ages Eligible for Study:   2 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Parent or guardian has signed informed consent and, if indicated per subject's age and institutional guidelines, subject has signed informed assent
  • Be medically diagnosed with spinal muscular atrophy (SMA)
  • Have onset of clinical signs and symptoms consistent with SMA at greater than 6 months of age
  • Be 2 to 12 years of age at screening
  • Be able to sit independently, but has never had the ability to walk independently
  • Have Motor Function Score (Hammersmith Functional Motor Scale - Expanded) greater than or equal to 10 and less than or equal to 54 at Screening
  • Be able to complete all study procedures, measurements and visits and parent or guardian and subject has adequately supportive psychosocial circumstances, in the opinion of the Investigator
  • Have an estimated life expectancy of greater than 2 years from Screening, in the opinion of the Investigator
  • Meet age-appropriate institutional criteria for use of anesthesia and sedation, if use is planned for study procedures
  • For subjects who have reached reproductive maturity, satisfy study contraceptive requirements

Exclusion Criteria:

  • Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for greater than 6 hours during a 24 hour period, at Screening
  • Medical necessity for a gastric feeding tube, where the majority of feeds are given by this route, as assessed by the Site Investigator
  • Severe contractures or severe scoliosis evident on X-ray examination at Screening
  • Hospitalization for surgery (i.e., scoliosis surgery, other surgery), pulmonary event, or nutritional support 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, including tumors, or abnormalities by MRI or CT that would interfere with the LP procedures or CSF circulation
  • Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
  • History of bacterial meningitis
  • Dosing with IONIS-SMN Rx in any previous clinical study
  • Prior injury (e.g., upper or lower limb fracture) or surgical procedure which impacts the subject's ability to perform any of the outcome measure testing required in the protocol and from which the subject has not fully recovered or achieved a stable baseline
  • Clinically significant abnormalities in hematology or clinical chemistry parameters or ECG, as assessed by the Site Investigator, at the Screening visit that would render the subject unsuitable for inclusion
  • Treatment with another investigational drug (e.g., oral albuterol or salbutamol, riluzole, carnitine, creatine, sodium phenylbutyrate, et.c), 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, antisense oligonucleotide therapy, or cell transplantation.
  • Ongoing medical condition that according to the Site Investigator 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 compromise the ability of the subject to undergo study procedures.
  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: NCT02292537

  Show 24 Study Locations
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
  More Information

Additional Information:
Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02292537     History of Changes
Other Study ID Numbers: ISIS 396443-CS4 
Study First Received: November 12, 2014
Last Updated: August 15, 2016

Keywords provided by Ionis Pharmaceuticals, Inc.:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
ISIS-SMN Rx
ISIS 396443
Cherish
IONIS-SMNRx
IONIS-SMN Rx

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 February 17, 2017