A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants
Condition: Muscular Atrophy, Spinal
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Atrophy
Intervention: Placebo; Risdiplam
Intervention description: Placebo will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).; Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Intervention MeSH terms: Risdiplam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Enrollment: 231.0
Sex: All
Minimum age: 2 Years
Maximum age: 25 Years
Healthy volunteers: No

Summary:

      Multi-center, randomized, double-blind, placebo-controlled study to assess the safety,
      tolerability, pharmacokinetics, pharmacodynamics, and efficacy of Risdiplam in adult and
      pediatric participants with Type 2 and Type 3 SMA. The study consists of two parts, an
      exploratory dose finding part (Part 1) of Risdiplam for 12 weeks and a confirmatory part
      (Part 2) of Risdiplam for 24 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of 5q-autosomal recessive SMA

          -  Negative blood pregnancy test at screening and agreement to comply with measures to
             prevent pregnancy and restrictions on sperm donation

          -  For Part 1: Type 2 or 3 SMA ambulant or non-ambulant

          -  For Part 2: 1) Type 2 or 3 SMA non-ambulant; 2) RULM entry item A greater than or
             equal to 2; 3) ability to sit independently as assessed by item 9 of the MFM

        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 administration of a SMN2-targeting antisense oligonucleotide,
             SMN2 splicing modifier or gene therapy either in a clinical study or as part of
             medical care

          -  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 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

          -  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 Risdiplam
             or to the constituents of its formulation

          -  Recent history (less than one year) of ophthalmological diseases

          -  Participants requiring invasive ventilation or tracheostomy