Clinical Trial: A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7034067 in Infants With Type1 Spinal Muscular Atrophy (Firefish)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Two Part Seamless, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7034067 in Infants With Type 1 Sp

Brief Summary: Open-label, multi-center clinical study is to assess the safety, tolerability, pharmacokinetic, pharmacodynamics, and efficacy of RO7034067 in infants with Type 1 spinal muscular atrophy (SMA). The study consists of two parts, an exploratory dose finding part (Part 1) and a confirmatory part (Part 2) which will investigate RO7034067 for 24-months at the dose selected in Part 1.

Detailed Summary:
Sponsor: Hoffmann-La Roche

Current Primary Outcome:

  • Recommended Part 2 Dose of RO7034067 [ Time Frame: 2 weeks ]
  • Part 2: Percentage of Infants who are Sitting Without Support at 12-months of Treatment Assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler development Third Edition (BSID-III) [ Time Frame: Month 12 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 25 months ]
  • Part 1: Maximum plasma concentration (Cmax) of RO7034067 [ Time Frame: Pre-dose (PrD) (Hour 0) and 2, 4, 6, hour post-dose (PoD) on Days 1, 28, 84, 364, 546, 728; PrD on Day 2; PrD and 4 hours PoD on Days 7, 14, 56, 119, 182, 245, 301, 427, 490, 609, 672 ]
  • Part 2: Maximum plasma concentration (Cmax) of RO7034067 [ Time Frame: 2, 4, 6, hours PoD on Day 1; PrD (Hour 0) on Days 2, 14, 119, 245, 364, 427, 490, 609, 728; PrD and 2, 4, 6 hours PoD on Days 28, 56, 182, 301, 546, 672 ]
  • Part 1: Area under the curve (AUC) of RO7034067 [ Time Frame: PrD (Hour 0) and 2, 4, 6, hour PoD on Days 1, 28, 84, 364, 546, 728; PrD on Day 2; PrD and 4 hours PoD on Days 7, 14, 56, 119, 182, 245, 301, 427, 490, 609, 672 ]
  • Part 2: Area under the curve (AUC) of RO7034067 [ Time Frame: 2, 4, 6, hours PoD on Day 1; PrD (Hour 0) on Days 2, 14, 119, 245, 364, 427, 490, 609, 728; PrD and 2, 4, 6 hours PoD on Days 28, 56, 182, 301, 546, 672 ]
  • Part 1: Concentration at the end of a dosing interval (Ctrough) of RO7034067 [ Time Frame: PrD (Hour 0) Days 1, 2, 7, 14, 28, 56, 84, 119, 364, 546 ]
  • Part 2: Concentration at the end of a dosing interval (Ctrough) of RO7034067 [ Time Frame: PrD (Hour 0) on Days 2, 14, 28, 56, 119, 182, 301, 546, 672 ]
  • Time to Death [ Time Frame: Baseline up to 25 Months ]
  • Time to Permanent Ventilation [ Time Frame: Baseline up to 25 Months ]
  • Survival of Motor Neuron (SMN) Protein Levels in Blood [ Time Frame: pre-dose on Day 1, 14, 28, 119, 245, 364, 609, 728 ]
  • Survival Motor Neuron (SMN) Messenger Ribonucleic Acid (mRNA) Levels in Blood [ Time Frame: Day 1, 14, 28, 245, 364, 609, 728 ]
  • Change From Baseline in the Total Raw Score of the BSID-III Gross Motor Scale at Month 12 and 24 [ Time Frame: Baseline, Month 12, Month 24 ]
  • Percentage of Infants who Achieve the Attainment Levels of the Motor Milestones Assessed in the Hammersmith Infant Neurological Examination Module 2 (HINE-2) at Month 12 and 24 [ Time Frame: Month 12, Month 24 ]
  • Percentage of Infants who Achieve Highest Motor Milestone as Assessed in the BSID-III Gross Motor Scale [ Time Frame: Month 12, Month 24 ]
  • Percentage of Infants who Achieve a Score of 40 or Higher in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) at Month 12 [ Time Frame: Month 12 ]
  • Percentage of Infants who Achieve a Reduction of 30 Degrees in Their Phase Angle From Baseline, as Measured by Respiratory Inductance Plethysmography at Month 12 [ Time Frame: Baseline, Month 12 ]
  • Percentage of Infants who Achieve an Increase of at Least 0.3 millivolt From Baseline in Their Compound Muscle Action Potential Negative Peak Amplitude at Month 12 and 24 [ Time Frame: Baseline, Month 12, Month 24 ]
  • Time to Death or Permanent Ventilation, Whichever Occurred First [ Time Frame: Baseline up to 25 Months ]
  • Percentage of Infants who are Alive Without Permanent Ventilation at Month 12 and 24 [ Time Frame: Month 12, Month 24 ]
  • Percentage of Infants who are Sitting Without Support at 24-months [ Time Frame: Month 24 ]
  • Percentage of Infants who are Stands Alone as Assessed in Item 40 of the BSID-III Gross Motor Scale at Month 24 [ Time Frame: Month 24 ]
  • Percentage of Infants who are Walks Alone as Assessed in Item 42 of the BSID-III Gross Motor Scale at Month 24 [ Time Frame: Month 24 ]


Original Secondary Outcome: Same as current

Information By: Hoffmann-La Roche

Dates:
Date Received: September 21, 2016
Date Started: December 24, 2016
Date Completion: May 30, 2020
Last Updated: April 27, 2017
Last Verified: April 2017