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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT03032172
• Date of registration: 24/01/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy Jewelfish
• Scientific 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
• Date of first enrolment: March 3, 2017
• Target sample size: 174
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03032172
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Poland, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key 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



Age minimum: 6 Months
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Drug: Risdiplam

Primary Outcome(s)

Mean Plasma Concentration of Risdiplam Metabolite [Time Frame: Up to 2 years]

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 [Time Frame: Baseline up to 5 years]

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) [Time Frame: Baseline up to 5 years]

Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam [Time Frame: Up to 2 years]

Cmax of Risdiplam Metabolite [Time Frame: Up to 2 years]

Concentration of Risdiplam at the End of Dosing Interval (Ctrough) [Time Frame: Up to 2 years]

Maximum Plasma Concentration (Cmax) of Risdiplam [Time Frame: Up to 2 years]

Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments [Time Frame: Baseline up to 5 years]

AUC of Risdiplam Metabolite [Time Frame: Up to 2 years]

Tanner Staging Among all Participants Aged From 9 to 17 Years [Time Frame: Baseline up to 5 years]

Ctrough of Risdiplam Metabolite [Time Frame: Up to 2 years]

Mean Plasma Concentration of Risdiplam [Time Frame: Up to 2 years]

Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments [Time Frame: Baseline up to 5 years]

Secondary Outcome(s)

SMN messenger Ribonucleic Acid (mRNA) Level in Blood [Time Frame: Up to 2 years]

SMN Protein Levels in Blood [Time Frame: Up to 2 years]

Secondary ID(s)

2023-506739-14-00

2016-004184-39

BP39054

Source(s) of Monetary Support

Please refer to primary and secondary sponsors