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

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02908685
First received: September 19, 2016
Last updated: August 3, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
Muscular Atrophy, Spinal Drug: Placebo Drug: RO7034067 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 3 Spinal Muscular Atrophy Patients

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 186
Actual Study Start Date: October 20, 2016
Estimated Study Completion Date: May 7, 2020
Estimated Primary Completion Date: April 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Group A: Adolescents and Adults (RO7034067)
Adolescent and adult participants aged 12-25 years will receive RO7034067 for 12 weeks. Once 12-week treatment is completed and Part 2 dose is established, participants will be switched to Part 2 dose and will be followed-up in open label extension (OLE) phase.
Drug: Placebo
Placebo will be administered orally.
Drug: RO7034067
RO7034067 will be administered orally.
Placebo Comparator: Part 1 Group A: Adults and Adolescents (Placebo)
Adolescent and adult participants aged 12-25 years will receive placebo matching to RO7034067 for 12 weeks. Once 12-week treatment is completed placebo participants will be will be given the choice to switch to active treatment in OLE phase.
Drug: Placebo
Placebo will be administered orally.
Drug: RO7034067
RO7034067 will be administered orally.
Placebo Comparator: Part 1 Group B: Children (Placebo)
Children aged 2-11 years will receive placebo matching to RO7034067 for 12 weeks. Once 12-week treatment is completed placebo participants will be will be given the choice to switch to active treatment in OLE phase.
Drug: Placebo
Placebo will be administered orally.
Drug: RO7034067
RO7034067 will be administered orally.
Experimental: Part 1 Group B: Children (RO7034067)
Children aged 2-11 years will receive RO7034067 for 12 weeks. Once 12-week treatment is completed and Part 2 dose is established, participants will be switched to Part 2 dose and will be followed-up in OLE phase.
Drug: Placebo
Placebo will be administered orally.
Drug: RO7034067
RO7034067 will be administered orally.
Placebo Comparator: Part 2: Placebo
Participants aged 2-25 years will receive placebo matching to RO7034067. After 12-month primary analysis (to be performed once the last participant completes the 12-month treatment), placebo participants will be switched to active treatment (RO7034067). After 24-month treatment, participants will be offered the opportunity to enter the OLE phase.
Drug: Placebo
Placebo will be administered orally.
Experimental: Part 2: RO7034067
Participants aged 2-25 years will receive RO7034067 at the dose decided during Part 1 of the study, for up to 24 months. After 24-month treatment, participants will be offered the opportunity to enter the OLE phase.
Drug: RO7034067
RO7034067 will be administered orally.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Part 1: Type 2 or 3 SMA ambulant or non-ambulant. For Part 2: Type 2 or 3 SMA non-ambulant
  • Confirmed diagnosis of 5q-autosomal recessive SMA For Part 2: 1) revised upper limb module(RULM) entry item A greater than or equal to [>=] 2; 2) ability to sit independently as assessed by item 9 of the motor function measure (MFM)
  • Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation

Exclusion Criteria:

  • Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer
  • Concomitant or previous participation at any time in a Survival of motor neuron (SMN)-2 targeting antisense oligonucleotide, SMN2 splicing modifier or gene therapy study
  • Any history of cell therapy
  • Hospitalization for a pulmonary event within the last 2 months or planned at time of screening
  • Surgery for scoliosis or hip fixation in the one year preceding screening or planned within the next 18 months
  • Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
  • Presence of clinically significant electrocardiogram (ECG) abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants as determined by the Investigator
  • Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration
  • Any inhibitor of cytochrome P450 (CYP) 3A4 and/or any Organic Cation Transporter 2 (OCT-2) and multidrug and toxin extrusion (MATE) substrates taken within 2 weeks and/or any inducer of CYP3A4 taken within 4 weeks (or within 5-times the elimination half-life, whichever is longer) prior to dosing or participants taking any nutrients known to modulate CYP3A activity
  • Recently initiated treatment (within less than [<] 6 months prior to randomization) with oral salbutamol or another beta 2-adrenergic agonist taken orally
  • Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed - Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to RO7034067 or to the constituents of its formulation
  • Recent history (less than one year) of ophthalmological diseases
  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: NCT02908685

Contacts
Contact: Reference Study ID Number: BP39055 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Belgium
UZ Leuven Gasthuisberg Recruiting
Leuven, Belgium, 3000
France
Hopital Armand Trousseau Recruiting
Paris, France, 75571
Germany
Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen Recruiting
Freiburg, Germany, 79106
Italy
Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile Recruiting
Roma, Lazio, Italy, 00168
Fondazione IRCCS Istituto Neurologico "Carlo Besta"; UO di Neurologia dello Sviluppo Recruiting
Milano, Lombardia, Italy, 20133
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Additional Information:
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02908685     History of Changes
Other Study ID Numbers: BP39055
2016-000750-35 ( EudraCT Number )
Study First Received: September 19, 2016
Last Updated: August 3, 2017

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 August 18, 2017