Spinal Muscular Atrophy (SMA) MedDRA version: 20.1 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: RO7034067
Product Code: RO7034067/F06 + solvente (RO
Pharmaceutical Form: Powder and solvent for oral solution
Current Sponsor code: RO7034067/F06
Other descriptive name: RO7034067
Conce
Sponsors
F. HOFFMANN - LA ROCHE LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Males and females 12 to 60 years of age inclusive (at screening). - Confirmed diagnosis of 5q-autosomal recessive SMA, including: •Genetic confirmation of homozygous deletion or heterozygosity predictive of loss of function of the SMN1 gene, •Clinical symptoms attributable to Type 2 or Type 3 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 (all women of childbearing potential, including those who have had a tubal ligation), and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 - Lactating women - Suspicion of regular consumption of drugs of abuse - Positive urine test for drugs of abuse or alcohol at the screening or Day - 1 visit - Presence of clinically significant ECG abnormalities before study drug administration - Presence of clinically significant cardiovascular, blood pressure, and heart rate measures - History of malignancy if not considered cured - Significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the Columbia-Suicide Severity Rating Scale (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 - Use of any OCT-2 and MATE substrates within 2-weeks before dosing - Use of the following medications within 90 days prior to enrollment: riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, agents anticipated to increase or decrease muscle strength, agents with known or presumed histone deacetylase (HDAC) inhibitory effect, and medications with known phototoxicity liabilities (e.g., oral or topical retinoids including over-the-counter formulations, amiodarone. Use of inhaled corticosteroids is allowed. - Recently initiated treatment (within = 6 months before enrollment and have shown good tolerance are allowed. The dose of ß2-adrenergic agonist should remain stable as much as possible for the duration of the study. Use of inhaled ß2-adrenergic agonists (e.g., for the treatment of asthma) is allowed. - Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine is not allowed. Use of other medications known to or suspected of causing retinal toxicity within one year prior to enrollment is not allowed - Clinically significant abnormalities in laboratory test results - Donation or loss of blood >= 10% of blood volume within three months prior to screening - 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 patient in this study - Recent history (less than one year) of ophthalmological diseases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the safety and tolerability of RO7034067; •To investigate the pharmacokinetics (PK) of RO7034067 and metabolites as appropriate. ;Secondary Objective: •To investigate the PK/ pharmacodynamics (PD) relationship of RO7034067. The PD investigations will include analyses of Survival of motor neuron (SMN) mRNA splice forms and SMN protein. ;Primary end point(s): 1.Incidence and severity of adverse events and serious adverse events. 2.Incidence of treatment discontinuations due to adverse events. 3.Incidence of clinically significant abnormal vital sign, laboratory, and ECG abnormalities. 4.Incidence of clinically significant findings on ophthalmological examination. 5.Incidence of suicidal ideation or behavior (C-SSRS). 6.Mean plasma concentrations of RO7034067 and metabolites. 7.Peak plasma concentration (Cmax). 8.Area under the curve (AUC). 9.Concentration at the end of a dosing interval (Ctrough) to assess steady-state. ;Timepoint(s) of evaluation of this end point: 1-4. Up to 160 weeks. 5. Screening (Day-30 to -2), Day-1, Day 119, 182, 364, 546, 728, at follow-up visit 1 (Week 112). 6-9. Days 1, 7, 14, 28, 56, 119, 183, 245, 301, 365, 490, 609, 729, at follow-up visit 1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.SMN mRNA in blood. 2.SMN protein levels in blood. ;Timepoint(s) of evaluation of this end point: 1.Days -1, 1, 7, 14, 28, 183, 365, 729, at follow-up visit 1. 2.Day -1, Day 7, 14, 28, 183, 365, 729, at follow-up visit 1. | — |
Countries
Belgium, France, Germany, Italy, Netherlands, Poland, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line
F.Hoffmann-La Roche Ltd
Outcome results
None listed