A study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the study medication RO7034067 in adult and pediatric patients (12-17 years) with spinal muscular atrophy (SMA).

ICTRP Trial ID
NCT03032172 (ICTRP)

Official title (approved by ethics committee)
AN OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS/PHARMACODYNAMICS OF RISDIPLAM (RO7034067) IN ADULT AND PEDIATRIC PATIENTS WITH SPINAL MUSCULAR ATROPHY (BASEC)

Academic title
An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Risdiplam (RO7034067) in Adult and Pediatric Patients With Spinal Muscular Atrophy (ICTRP)

Public title
A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy (ICTRP)

Disease under investigation
Spinal Muscular Atrophy (ICTRP)

Intervention under investigation
Drug: Risdiplam (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
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

- 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 with the
exception of studies of olesoxime, AVXS-101, or nusinersen

- 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 (ICTRP)

not available

Primary and secondary end points
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Scale, V 4.0;Percentage of Participants With Emergence or Worsening of Symptoms As Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) (Adult Version for Adults and Adolescents, Pediatric Version for Patients Aged 6-11 Years);Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments;Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments;Tanner Staging Among all Participants Aged From 9 to 17 Years;Mean Plasma Concentration of Risdiplam;Maximum Plasma Concentration (Cmax) of Risdiplam;Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam;Concentration of Risdiplam at the End of Dosing Interval (Ctrough);Mean Plasma Concentration of Risdiplam Metabolite;Cmax of Risdiplam Metabolite;AUC of Risdiplam Metabolite;Ctrough of Risdiplam Metabolite (ICTRP)

SMN messenger Ribonucleic Acid (mRNA) Level in Blood;SMN Protein Levels in Blood (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Clinical Trials, Hoffmann-La Roche (ICTRP)

Secondary trial IDs
2016-004184-39, 2023-506739-14-00, BP39054 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03032172 (ICTRP)