A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy
A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy
This is a multi-center, exploratory, non-comparative, and open-label study to investigate the
 safety, tolerability, PK, and PK/PD relationship of risdiplam in adults, children and infants
 with Spinal Muscular Atrophy (SMA) previously enrolled in Study BP29420 (Moonfish) with the
 splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101.
Inclusion Criteria:

 -  Confirmed diagnosis of 5q-autosomal recessive SMA

 -  Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier RO6885247
 or previous treatment with any of the following: 1.) Nusinersen (defined as having
 received >= 4 doses of nusinersen, provided that the last dose was received >= 90 days
 prior to screening) or 2.) Olesoxime (provided that the last dose was received <= 12
 months and >= 90 days prior to screening) or 3.) AVXS-101 (provided that the time of
 treatment was >= 12 months 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

 -  For women of childbearing potential: negative blood pregnancy test at screening,
 agreement to remain abstinent (refrain from heterosexual intercourse) 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 participants aged 2 years or younger at screening: 1.) Parent or caregiver of
 participant 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; 2.) Parent or caregiver of participant is
 willing to consider the use of non-invasive ventilation, as recommended by the
 Investigator during the study

 Exclusion Criteria:

 -  Inability to meet study requirements

 -  Concomitant participation in any investigational drug or device study

 -  With the exception of studies of olesoxime, AVXS-101, or nusinersen: 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

 -  Any history of gene or cell therapy, with the exception of AVXS-101

 -  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 < 2 years, hospitalization for a pulmonary event within 2 months
 prior to screening and pulmonary function not fully recovered at the time of screening

 -  Lactating women

 -  Suspicion of regular consumption of drugs of abuse

 -  For adults and adolescents only, positive urine test for drugs of abuse or alcohol at
 screening or Day -1 visit

 -  Presence of clinically significant electrocardiogram (ECG) abnormalities before study
 drug administration from average of triplicate measurement or cardiovascular disease

 -  History of malignancy if not considered cured

 -  For participants 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

 -  Recently initiated treatment for spinal muscular atrophy (within <6 weeks 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 risdiplam
 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

 -  Any prior use of an inhibitor or inducer of FMO1 or FMO3 taken within 2 weeks (or
 within 5 elimination half-lives, whichever is longer) prior to dosing