Clinical Trial: A Study to Assess the Safety and Tolerability of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA).

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2, Randomized, Double-blind, Sham-procedure Controlled Study to Assess the Safety and Tolerability and Explore the Efficacy of ISIS 396443 (BIIB058) Administered Intrathecally in Subjects With

Brief Summary: The primary objective of Part 1 of this study is to assess the safety and tolerability of Nusinersen in participants with SMA who are not eligible to participate in the clinical studies ISIS 396443-CS3B (NCT02193074) or ISIS 396443-CS4 (NCT02292537). The secondary objective of Part 1 of this study is to examine the pharmacokinetics (PK) of Nusinersen in participants with SMA. The primary objective of Part 2 of this study is to assess the long-term safety and tolerability of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments. The secondary objective of Part 2 of this study is to examine the PK of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments.

Detailed Summary: Part 2 is an Open Label extension phase.
Sponsor: Biogen

Current Primary Outcome:

  • Number of participants with adverse events and serious adverse events [ Time Frame: Up to 44 months ]
    Part 1: 14 months Part 2: 30 months
  • Change from Baseline in clinical laboratory parameters [ Time Frame: Baseline and 14 months (Part 1) and 30 months (Part 2) ]
    Assessed by the following laboratory tests: Blood chemistry: total protein, albumin, creatinine, cystatin C, creatine phosphokinase, blood urea nitrogen, total bilirubin (direct and indirect), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glucose, calcium, phosphorus, chloride, sodium, potassium. Hematology: red blood cells, hemoglobin, hematocrit, platelets, white blood cells, white blood cell differential. Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, red blood cells, white blood cells, epithelial cells, bacteria, casts, crystals
  • Change from Baseline in electrocardiograms (ECGs) [ Time Frame: Baseline and 14 months (Part 1) and 30 months (Part 2) ]
  • Change from Baseline in vital signs [ Time Frame: Baseline and 14 months (Part 1) and 30 months (Part 2) ]
    Vital signs will be assessed by: Resting systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature, pulse oximetry, and transcutaneous carbon dioxide
  • Change from Baseline in neurological examination outcomes [ Time Frame: Baseline and 14 months (Part 1) and 30 months (Part 2) ]
    Assessed by the following neurological examination: mental status, level of consciousness, sensory motor fun

    Original Primary Outcome:

    • Number of participants with adverse events and serious adverse events [ Time Frame: 14 months ]
    • Change from Baseline in clinical laboratory parameters [ Time Frame: Baseline and 14 months ]
      Assessed by the following laboratory tests: Blood chemistry: total protein, albumin, creatinine, cystatin C, creatine phosphokinase, blood urea nitrogen, total bilirubin (direct and indirect), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glucose, calcium, phosphorus, chloride, sodium, potassium. Hematology: red blood cells, hemoglobin, hematocrit, platelets, white blood cells, white blood cell differential. Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, red blood cells, white blood cells, epithelial cells, bacteria, casts, crystals
    • Change from Baseline in electrocardiograms (ECGs) [ Time Frame: Baseline and 14 months ]
    • Change from Baseline in vital signs [ Time Frame: Baseline and 14 months ]
      Vital signs will be assessed by: Resting systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature, pulse oximetry, and transcutaneous carbon dioxide
    • Change from Baseline in neurological examination outcomes [ Time Frame: Baseline and 14 months ]
      Assessed by the following neurological examination: mental status, level of consciousness, sensory motor function, cranial nerve function, and reflexes


    Current Secondary Outcome:

    • Nusinersen plasma concentration [ Time Frame: Up to Day 897 ]

      Part 1:

      Day 1 post dose, Days 64, 183, and end of Part 1

      Part 2 (participants randomized to drug):

      Day 1 post dose, Days 239, 477, 715, and Part 2 final follow-up

      Part 2 (participants randomized to sham):

      Day 1 post dose, Days 64, 183, 540, 778, and Part 2 Final follow-up

    • Nusinersen cerebrospinal fluid (CSF) concentration [ Time Frame: Up to Day 897 ]

      Part 1:

      Predose Days 1, 15, 29, 64, 183, 302

      Part 2 (participants randomized to drug):

      Predose Days 1, 120, 239, 358, 477, 596, 715

      Part 2 (participants randomized to sham):

      Predose Days 1, 15, 29, 64, 183, 302, 421, 540, 659, 778



    Original Secondary Outcome:

    • ISIS 396443 plasma concentration [ Time Frame: 4 hours post-dose on Day 1 and pre-dose on Days 64, 183 and 422 ]
    • ISIS 396443 cerebrospinal fluid (CSF) concentration [ Time Frame: Pre-dose on Days 1, 15, 29, 64, 183 and 302 ]


    Information By: Biogen

    Dates:
    Date Received: May 14, 2015
    Date Started: August 19, 2015
    Date Completion: April 9, 2019
    Last Updated: May 4, 2017
    Last Verified: May 2017