Spinal Muscular Atrophy MedDRA version: 17.0 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: RO6885247/F03
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: n.a.
CAS Number: 1449598-06-4
Current Sponsor code: RO6885247
Other descriptive name: n.a.
Concentration
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Males and females, aged 2 to 55 years inclusive - Confirmed diagnosis of 5q-autosomal recessive SMA (Types 1 to 3) - Able and willing to provide informed consent and to comply with the study protocol. Alternatively, a legally authorized representative must be able to consent for the patient and assent must be given by the subject wherever possible. - Female patients of childbearing potential and male patients with a female partner of childbearing potential must agree with the required contraceptive methods as defined per protocol. Are the trial subjects under 18? yes Number of subjects for this age range: 36 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening - Concomitant or previous participation in a SMN2-targeting antisense oligonucleotide study within 12 months prior to screening - Concomitant or previous participation at any time in a gene therapy study - Hospitalization for pulmonary event within the last 2 months or planned at the time of screening - Surgery for scoliosis in the last 6 months from screening or planned within 6 months from screening - Unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease - Clinically relevant ECG abnormalities at screening or baseline; personal or family history (first degree relatives) of congenital long QT syndrome - Clinically significant abnormalities in laboratory test results at screening - Any concomitant disease or condition that could interfere with the conduct of the study, or pose an unacceptable risk to the subject in this study - Use of prohibited medications as per protocol within 90 days prior to randomization. Patients who are on inhaled corticosteroids, administered either through a nebulizer or an inhaler, are allowed. - Recently initiated treatment (within <6 months prior to randomization) with oral salbutamol or another beta2-adrenergic agonist taken orally is not allowed. Patients who have been on oral salbutamol (or another beta2-adrenergic agonist) for at least 6 months before randomization are allowed. Use of inhaled beta2-adrenergic agonists is allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of 12 weeks treatment with RO6885247 in adult and pediatric patients with spinal muscular atrophy (SMA) ;Secondary Objective: Pharmacokinetics •To investigate the multiple-dose pharmacokinetics of RO6885247 and its metabolite(s), if appropriate •To assess the potential effect of food on the pharmacokinetics of RO6885247 Pharmacodynamics •To investigate pharmacodynamic (PD) effects of RO6885247 as assessed by Survival of Motor Neuron 2 (SMN2) splicing modification and increase in SMN protein •To investigate the pharmacokinetic (PK)/PD relationship of RO6885247 by PK/PD modeling (PD to include SMN2 messenger RNA (mRNA) and SMN protein) •To investigate the effect of 12 weeks of treatment with RO6885247 on muscle electrophysiology as assessed by Compound Muscle Action Potential (CMAP) •To investigate the effect of 12 weeks of treatment with RO6885247 on Electrical Impedance Myography (EIM) (optional);Primary end point(s): Safety: Incidence of adverse events (AEs);Timepoint(s) of evaluation of this end point: Up to 20 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Pharmacokinetics: RO6885247 plasma concentrations 2. Pharmacokinetics: RO6885247 exposure, area under the concentration-time curve (AUC-tau, over the 24-hour dosing interval) 3. Pharmacodynamics: SMN protein levels in blood 4. Effect of RO6885247 on muscle electrophysiology, as assessed by Compound Muscle Action Potential (CMAP) 5. Effect of RO6885247 on Electrical Impedance Myography 6. Pharmacodynamics: In vivo splicing modification of SMN2 mRNA in blood;Timepoint(s) of evaluation of this end point: 1. Up to 16 weeks 2. Up to 12 weeks 3-6: Up to 20 weeks | — |
Countries
Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed