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A Study of RO7034067 in Adult and Pediatric Participants With Spinal Muscular Atrophy (Jewelfish)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT03032172
First received: January 24, 2017
Last updated: June 20, 2017
Last verified: June 2017
  Purpose
This is a multi-center, exploratory, non-comparative and open-label study to investigate the safety, tolerability, pharmacokinetic (PK) and PK/pharmacodynamic (PD) relationship of RO7034067 in adults and children with Type 2 and Type 3 Spinal Muscular Atrophy (SMA) who have been previously treated with a survival of motor neuron 2 (SMN2)-targeting therapy.

Condition Intervention Phase
Spinal Muscular Atrophy Drug: RO7034067 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of RO7034067 in Adult and Pediatric Patients With Spinal Muscular Atrophy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: From screening up to 160 weeks ]
  • Percentage of Participants With Suicidal Ideation or Behavior, As Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to 104 weeks (assessed at baseline [Day1]; Days 119, 182, 364, 546, 728; early withdrawal visit [up to Week 104]) ]
  • Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments [ Time Frame: Baseline up to 104 weeks (assessed at Weeks 8, 17, 26, 35, 43, 52, 61, 70, 78, 87, 96, 104; early withdrawal visit [up to Week 104]) ]
  • Tanner Staging Among all Participants Aged From 12 to 17 Years [ Time Frame: Month 24 ]
  • Mean Plasma Concentration of RO7034067 [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • Maximum Plasma Concentration (Cmax) of RO7034067 [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • Area Under the Plasma Concentration Versus Curve (AUC) of RO7034067 [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • Concentration of RO7034067 at the End of Dosing Interval (Ctrough) [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • Mean Plasma Concentration of RO7034067 Metabolite [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • Cmax of RO7034067 Metabolite [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • AUC of RO7034067 Metabolite [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]
  • Ctrough of RO7034067 Metabolite [ Time Frame: 1, 2, 4, 6 hrs postdose on Days 1, 28, 56, 365, 609; predose (0 hr) on Days 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609; Day 729; early withdrawal visit (up to Week 104); FU visit 1 (Week 112) ]

Secondary Outcome Measures:
  • SMN messenger Ribonucleic Acid (mRNA) Level in Blood [ Time Frame: Day -1; predose (0 hr) on Days 7, 14, 183; 4 hr postdose on Days 1, 28, 365; Day 729; early withdrawal visit (up to Week 104); follow-up visit 1 (Week 112) ]
  • SMN Protein Levels in Blood [ Time Frame: Day -1; predose (0 hr) on Days 7, 14, 183; 4 hr postdose on Days 28, 365; Day 729; early withdrawal visit (up to Week 104); follow-up visit 1 (Week 112) ]

Estimated Enrollment: 24
Actual Study Start Date: March 2, 2017
Estimated Study Completion Date: January 31, 2021
Estimated Primary Completion Date: January 31, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RO7034067
Participants will receive multiple doses of RO7034067 orally once daily for 24 months.
Drug: RO7034067
RO7034067 will be administered orally once daily.

  Eligibility

Ages Eligible for Study:   12 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of 5q-autosomal recessive SMA
  • Previous participation in a study with an SMN2-targeting antisense oligonucleotide or SMN2 splicing modifier other than RO7034067
  • Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation

Exclusion Criteria:

  • Inability to meet study requirements
  • Concomitant participation in any investigational drug or device study
  • Previous participation in an SMN2-targeting antisense oligonucleotide or SMN2 splicing modifier study other than RO7034067 within 90 days prior to screening
  • Previous participation in any investigational drug or device study, other than SMN2 targeting antisense oligonucleotide or SMN2 splicing modifier study, within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer
  • Any history of gene or cell therapy
  • 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 indicating a safety risk for the participant as determined by the Investigator.
  • Significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the C-SSRS
  • 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
  • Recently initiated treatment (within less than [<] 6 months prior to enrollment) 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
  • Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study
  • Recent history (less than one year) of ophthalmological diseases that would interfere with the conduct of the study as assessed by an ophthalmologist. Participants in whom Organic Cation Transporter or Optical Coherence Tomography (OCT) measurement of sufficient quality cannot be obtained at screening will not be enrolled
  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: NCT03032172

Contacts
Contact: Reference Study ID Number: BP39054 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, New York
Columbia University Medical Center; The Neurological Institute of New York Recruiting
New York, New York, United States, 10032
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: NCT03032172     History of Changes
Other Study ID Numbers: BP39054
2016-004184-39 ( EudraCT Number )
Study First Received: January 24, 2017
Last Updated: June 20, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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 June 27, 2017