Clinical Trial: A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7034067 in Type 2 and 3 Spinal Muscular Atrophy Participants (Sunfish)

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

Official Title: A Two-Part Seamless, Multi-Center Randomized, Placebo-Controlled, Double-blind Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7034067 in Type 2 and

Brief Summary: Multi-center, randomized, double-blind, placebo-controlled, Phase II study to assess the safety, tolerability, pharmacokinetic, pharmacodynamics, and efficacy of RO7034067 in adult and pediatric patients with Type 2 and Type 3 spinal muscular atrophy (SMA). The study consists of two parts, an exploratory dose finding part (Part 1) of RO7034067 for 12-weeks and a confirmatory part (Part 2) of RO7034067 for 24-months.

Detailed Summary:
Sponsor: Hoffmann-La Roche

Current Primary Outcome:

  • Part 2: Change from baseline in the total motor function measure 32 (MFM-32) score at Month 12 [ Time Frame: Baseline (Day -1) and Month 12 ]
  • Part 1: Recommended Part 2 Dose of RO7034067 [ Time Frame: 120 days ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Survival of Motor Neuron 2 (SMN2) Messenger Ribonucleic Acid (mRNA) Levels in Blood [ Time Frame: Part 2: Days -1, 1, 7, 28, 120, 246, 365, 729 ]
  • Survival of Motor Neuron (SMN) Protein Levels in Blood [ Time Frame: Part 2: Days -1, 7, 28, 120, 246, 365, 729 ]
  • Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Percentage of Participants who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor function measure (MFM) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in the Best Sniff Nasal Inspiratory Pressure (SNIP) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in Forced Vital Capacity (FVC) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in the Peak Cough Flow (PCF) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in Neuromuscular Disease Domain Score as Assessed by Pediatric Quality of Life Inventory (PedsQL) 3.0 Neuromuscular Module at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in Total Score of the PedsQL 4.0 Generic Core Scale at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Percentage of Participants who Experience at Least one Disease Related Adverse Event [ Time Frame: Baseline up to Month 12 ]
  • Part 1 and 2: Maximum plasma concentration (Cmax) of RO7034067 [ Time Frame: Part 1 and 2: 1, 2, 4, 6 hours post dose on Day 1; Pre-dose (Hour 0) on Days 7, 14, 56 (part 2), 120, 246, 490, 729; pre-dose (Hour 0) and 1, 2, 4, 6 hours post dose on Days 28, 56 (part 1), 365, 609 ]
  • Part 1 and 2: Area under the curve (AUC) of RO7034067 [ Time Frame: Part 1 and 2: 1, 2, 4, 6 hours post dose on Day 1; Pre-dose (Hour 0) on Days 7, 14, 56 (part 2), 120, 246, 490, 729; pre-dose (Hour 0) and 1, 2, 4, 6 hours post dose on Days 28, 56 (part 1), 365, 609 ]
  • Part 1 and 2: Concentration at the end of a dosing interval (Ctrough) of RO7034067 [ Time Frame: Part 1 and 2: Pre-dose (Hour 0) on Days 7, 14, 28, 56, 120, 246, 365, 490, 609, 729 ]
  • Percentage of Participants With adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Baseline up to 24 months ]
  • Change From Baseline in the MFM Domain 1 (D1) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in the MFM Domain 2 (D2) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in the MFM Domain 3 (D3) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Change From Baseline in the Total Combined Scores of MFM Domains 1 and 2 at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
  • Percentage of Participants With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline (Day-1), Day 120, Day 248, Day 386, Day 647, Day 729 ]


Original Secondary Outcome: Same as current

Information By: Hoffmann-La Roche

Dates:
Date Received: September 19, 2016
Date Started: October 20, 2016
Date Completion: May 7, 2020
Last Updated: April 27, 2017
Last Verified: April 2017