Efficacy and Safety of Surlorian in Adults with Autosomal Dominant RYR1-Related Myopathy: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2025-522343-18-00
Protocol: CL2-210-02
Sponsor: Rycarma Therapeutics Inc.

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Diseases & Conditions

Congenital myopathy

Objectives

The primary objective is to evaluate the efficacy of surlorian in adults with autosomal dominant RYR1-related myopathy by assessing its impact on muscle strength and fatigability via the 1-minute sit-to-stand test (1-MSST). Secondary objectives include the assessment of physical performance and fatigue through the 6-minute walk test (6-MNWT), timed up and go test (TUG), 4-stair climb test (4-SCT), quantitative muscle assessment (QMA), and manual muscle testing (MMT). Additionally, the study evaluates participant-reported fatigue and physical function, alongside the safety and tolerability of the investigational product. 5, 4, 6.

Participants

This clinical trial involves 7 participants diagnosed with autosomal dominant RYR1-related myopathy. The study population consists of adults, including both males and females, within the age range of 18 to 65 years. Participants must have a confirmed genetic diagnosis of the condition and exhibit clinical evidence of proximal muscle weakness. Additionally, subjects are required to be able to walk 10 meters either independently or with the use of a cane. The primary objectives of the study are to evaluate the effects of surlorian on muscle strength and fatigability, specifically utilizing the 1-minute sit-to-stand test.

Plans and Procedures

This Phase 2, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of surlorian in adults diagnosed with autosomal dominant RYR1-related myopathy. The study utilizes a placebo comparison to assess changes in muscle strength and fatigability. The primary endpoint is the change from baseline in the 1-minute sit-to-stand test after approximately 28 days of dosing. Secondary objectives include evaluating various motor function assessments, patient-reported outcomes via questionnaires, and the incidence of adverse events. Safety monitoring involves vital signs, physical examinations, laboratory tests, electrocardiograms, and the Columbia Suicide Severity Rating Scale. The protocol involves a screening visit to confirm genetic diagnosis and clinical weakness, followed by a treatment period and subsequent assessments to determine the drug's effect compared to the placebo group.

Treatment

The experimental medication is Surlorian, administered as a film-coated tablet. The dosage is 300 mg, delivered via oral use.

The control group receives a Surlorian placebo.

Efficacy

The efficacy assessment in this study focuses on the impact of surlorian on muscle strength and fatigability in adults with autosomal dominant RYR1-related myopathy. The primary endpoint is the change from Day 1 in the 1-minute sit-to-stand test (1-MSST) after approximately 28 days of dosing, comparing the active treatment group to the placebo group.

Secondary efficacy parameters include the following assessments conducted after approximately 28 days of dosing:

Change from Day 1 in the 6-minute walk test (6 MNWT), timed up and go (TUG), 4-station chair stand test (4 SCT), and weight-scaled muscle strength as measured by the quantitative muscle assessment (QMA) and manual muscle testing (MMT).
Change from Day 1 in patient-reported outcomes using the PROMIS-Fatigue (PROMIS-F), PROMIS Physical Function (PROMIS PF), and International Physical Activity Questionnaire (IPAQ).

Inclusion and Exclusion Criteria

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Inclusion Criteria

Is an adult aged 18-65 years at the time of signing informed consent.
Has a confirmed genetic diagnosis of RYR1-RM with autosomal dominant mutation.
Has clinical evidence of weakness affecting any proximal muscle group(s) as assessed by the Investigator.
Can walk 10 m with or without a cane (no other walking aid allowed).

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Exclusion Criteria

Has severe pulmonary dysfunction at screening (e.g., FVC <40% predicted) or evidence of pulmonary exacerbation. Pulmonary exacerbation is an acute worsening of respiratory symptoms that result from a decline in lung function.
2.Has cardiac disease by history or at screening that in Investigator’s judgment is likely to worsen overall performance on efficacy measures during the trial (e.g., left ventricular ejection fraction < 40%).
Has a history of seizure disorder, neurologic disease, or neuromuscular disease other than RYR1-RM.
Has a history of chronic orthopaedic issues, any acute injury or expected surgery during the trial that may affect the ability to complete trial assessments.
Participants with screening alanine aminotransferase (ALT) levels >3 × upper limit of normal (ULN) or screening aspartate aminotransferase (AST) levels >5 × ULN (isolated elevations of total bilirubin <2 × ULN with direct bilirubin below the ULN will be included).
Received treatment with statins, proton pump inhibitors, or H2 blockers within 7 days or 5 half-lives, whichever is longer, prior to the first dose of IP.
Received treatment with sensitive or narrow therapeutic index CYP3A4 substrates within 7 days or 5 half-lives, whichever is longer, prior to the first dose of IP.
Received treatment with strong or moderate CYP2C8 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to the first dose of IP.
Has reported any suicidal ideation of Category 4 or 5 on the C-SSRS within 6 months prior to screening or any suicidal behaviour in the last 2 years prior to screening, as indicated by any ‘yes’ answers on the suicidal behaviour section of C-SSRS.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Yet Recruiting	30 Apr 2026	7
Germany	Recruiting	30 Apr 2026	21
The Netherlands	Not Yet Recruiting	30 Apr 2026	—
Spain	Not Yet Recruiting	30 Apr 2026	7
Netherlands	—	—	6