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/F13
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: Risdiplam
CAS Number: 1825352-65-5
Current Sponsor code: RO7034067/F13
Other desc
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Males and females 6 months 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 history, signs, or symptoms attributable to SMA - Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previous treatment with nusinersen (defined as having received >= 4 doses of nusinersen, provided that the last dose was received >=90 days prior to screening) or olesoxime (provided that the last dose was received = 90 days prior to screening) - Adequately recovered from any acute illness at the time of screening and considered well enough to participate in the opinion of the Investigator - Women of childbearing potential: Negative blood pregnancy test at screening, agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating eggs for at least 28 days after the final dose of study drug For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm -For patients aged 2 years or younger at screening: •Receiving adequate nutrition and hydration (with or without gastrostomy) at the time of screening, in the opinion of the Investigator •Medical care meets local accepted standard of care, in the opinion of the Investigator •Would be able to complete all study procedures, measurements and visits, and the parent or caregiver of the patient has adequately supportive psychosocial circumstances, in the opinion of the Investigator •Parent or caregiver of patient is willing to consider nasogastric, naso-jejunal or gastrostomy tube placement, as recommended by the Investigator, during the study to maintain safe hydration, nutrition and treatment delivery •Parent or caregiver of patient is willing to consider the use of non-invasive ventilation, as recommended by the Investigator during the study Are the trial subjects under 18? yes Number of subjects for this age range: 62 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 63 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 any investigational drug or device study, with the exception of studies with olesoxime or nusinersen,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 -Inadequate venous or capillary blood access for the study procedures, in the opinion of the Investigator -For patients aged 12 years, 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 -For patients aged > 6 years, 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 including the mother, if breastfeeding the patient -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 retinoids including over-the-counter formulations, amiodarone. Use of inhaled corticosteroids is allowed -Recently initiated treatment for SMA (within = 6 weeks 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
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 with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events scale, Version 4.0 2.Incidence of treatment discontinuations due to adverse events 3.Incidence of abnormal vital sign, laboratory, and ECG abnormalities 4.Incidence of clinically significant findings on ophthalmological examination 5.Incidence of clinically significant findings on neurological examination 6.Physical examination including examination of the skin, mouth, pharynx and larynx 7.Incidence of emergence or worsening of symptoms as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) (adult version for adults and adolescents, pediatric version for patients aged 6-11 years) 8.Mean plasma concentrations of RO7034067 and metabolites 9.Peak plasma concentration (Cmax) 10.Area under the curve (AUC) 11.Concentration at the end of a dosing interval (Ctrough) to assess steady-state ;Timepoint(s) of evaluation of this end point: 1-6. Up to 5 years 7. Aged 6 to 60 Years: Screening, Day-1, Day 182, 364, 546, 728, at extension phase and follow-up visit 1 (Week 112) 8-11. Aged 2 to 60 Years: Days 1, 14, 28, 91, 183, 273, 365, 456, 637, 729, at early withdrawal and at follow-up visit 1; Aged 6 month to 2 Years: Days 1, 14, 28, 91, 182, 273,364, 456, 546, 637, 728, every 26 weeks during the extension phase and at early withdrawal | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1.Aged 2 to 60 Years: Days -1, 1, 28, 91, 183, 365, 729, at early withdrawal, and at follow-up visit 1; Patients Aged 6 Months to <2 Years: Day 1, 28, 182, 364 and 728 and at early withdrawal 2.Aged 2 to 60 Years: Day -1, Day 28, 91, 183, 365, 729, at early withdrawal, and at follow-up visit 1; Patients Aged 6 Months to <2 Years: Day 1, 28, 182, 364 and 728 and at early withdrawal ;Secondary end point(s): 1.SMN mRNA in blood 2.SMN protein levels in blood | — |
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