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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 March 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: March 8, 2017
Last verified: March 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: 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: March 6, 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.rochegenentechtrials@roche.com

  Hide Study Locations
Locations
United States, California
Stanford University Medical Center Not yet recruiting
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital of Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children'S Medical Center; Dept of Neurology Not yet recruiting
Hartford, Connecticut, United States, 06106
United States, Florida
Nemours Children's Hospital Not yet recruiting
Orlando, Florida, United States, 32827
United States, Illinois
Ann and Robert H. Lurie Children Hospital of Chicago Not yet recruiting
Chicago, Illinois, United States, 60611
United States, Maryland
The Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Duke Clin Rsch Institute Not yet recruiting
Durham, North Carolina, United States, 27710
United States, Oregon
Oregon Health & Science Uni Not yet recruiting
Portland, Oregon, United States, 97239
United States, Utah
University of Utah Clinical Neurosciences Center Not yet recruiting
Salt Lake City, Utah, United States, 84132
Argentina
Hospital de Pediatria Dr. Garrahan; Inmunologia Not yet recruiting
Buenos Aires, Argentina, 1245
Australia, New South Wales
Sydney Children's Hospital Not yet recruiting
Randwick, New South Wales, Australia, 2031
Australia, Victoria
Royal Children's Hospital Not yet recruiting
Parkville, Victoria, Australia, 3052
Belgium
UZ Gent Not yet recruiting
Gent, Belgium, 9000
UZ Leuven Gasthuisberg Not yet recruiting
Leuven, Belgium, 3000
Chr de La Citadelle Not yet recruiting
Liège, Belgium, 4000
Canada, Alberta
Alberta Children's Hospital Division of Pediatric Neurology Not yet recruiting
Calgary, Alberta, Canada, T3B 6A8
Canada, Quebec
McGill University Health Center Not yet recruiting
Montreal, Quebec, Canada, H4A 3J1
France
Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique - L'ESCALE Not yet recruiting
Bron, France, 69677
Hopital Roger Salengro Not yet recruiting
Lille, France, 59037
CHU de Nantes - Hotel Dieu Not yet recruiting
Nantes, France, 44093
Hopital Armand Trousseau Recruiting
Paris, France, 75571
Germany
Universitätsklinikum Essen; Klinik für Kinderheilkunde I Not yet recruiting
Essen, Germany, 45147
Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen Recruiting
Freiburg, Germany, 79106
Italy
IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative Not yet recruiting
Roma, Lazio, Italy, 00165
Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile Recruiting
Roma, Lazio, Italy, 00168
IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative Not yet recruiting
Genova, Liguria, Italy, 16147
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia Not yet recruiting
Milano, Lombardia, Italy, 20122
Fondazione IRCCS Istituto Neurologico "Carlo Besta"; UO di Neurologia dello Sviluppo Recruiting
Milano, Lombardia, Italy, 20133
Azienda Ospedaliera Universitaria Policlinico G.Martino; Dip. Neurologia e Malattie neuromuscolari Not yet recruiting
Messina, Sicilia, Italy, 98125
Spain
Hospital Sant Joan De Deu Not yet recruiting
Esplugues De Llobregas, Barcelona, Spain, 08950
Hospital Universitari Vall d'Hebron; Servicio de Reumatologia Not yet recruiting
Barcelona, Spain, 08035
Hospital Universitario La Paz Not yet recruiting
Madrid, Spain, 280146
Sweden
Sahlgrenska Universitetssjukhuset, Östra Sjukhus; Drottning Silvias Barnsjukhus Not yet recruiting
Göteborg, Sweden, 416 85
Switzerland
Universitäts-Kinderspitalbeider Basel_Abteilung für Neuro- und Entwicklungspädiatrie Not yet recruiting
Basel, Switzerland, 4005
Taiwan
Kaohsiung Medical University Chung-Ho Hospital; Pediatric Neurology Not yet recruiting
Kaohsiung, Taiwan, 807
Turkey
Hacettepe University, School of Medicine; Pediatrics Department; Pediatrics Child Neurology Unit Not yet recruiting
Ankara, Turkey, 06100
United Kingdom
Great Ormond Street Hospital for Children Not yet recruiting
London, United Kingdom, WC1N 3JH
The Newcastle upon Tyne Hospitals NHS Foundation Trust Not yet recruiting
Newcastle upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More 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: March 8, 2017

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy, Spinal
Muscular Atrophy
Pathological Conditions, Anatomical
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on March 22, 2017