Autosomal Dominant RYR1-Related Myopathy
Conditions
Keywords
RYR1-Related Myopathy, Adults, Phase 2, Interventional, Surlorian, ARM210
Brief summary
This study is testing a medicine called surlorian in adults who have a genetic muscle condition known as autosomal dominant RYR1-related myopathy (RYR1-RM). The goal is to find out whether surlorian improves muscle weakness, and whether it is safe and well tolerated.
Detailed description
The study is taking place at several medical centers with doctors who specialize in treating people with RYR1-RM. Everyone in the study will receive both surlorian and a placebo (a "dummy" treatment) at different times, but neither the participants nor the study staff will know which one they are getting during each period. During Treatment period 1, participants will be randomly assigned to receive either surlorian or a placebo, which will be followed up by a washout period. Following the washout, in Treatment period 2, participants will switch and receive the opposite treatment from what they received in the first period. This main part of the study lasts about 16 weeks. After finishing the main, placebo-controlled part of the study participants may be able to join an open-label extension lasting approximately 12 months. In this extension, everyone receives surlorian.
Interventions
DRUGSurlorian
300 mg administered once a day
OTHERPlacebo
administered once a day
Sponsors
RyCarma Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Can understand the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with all protocol requirements * Confirmed genetic diagnosis of RYR1-RM with autosomal dominant mutation * 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) * Is either a female of non-childbearing potential or male or female, who agrees to use highly effective contraception/preventive exposure measures from the time of first dose of IP (for a male participant) or the signing of the informed consent form (ICF) (for a female participant) during the trial, and until 7 days after the last dose of IP.
Exclusion criteria
* Unable or unwilling to understand and comply with protocol requirements or unlikely to complete the study as planned, as judged by the Investigator * Any clinically significant medical condition that, in the opinion of the Investigator, would interfere with the study * Females who are pregnant, breastfeeding or intend to become pregnant, or of childbearing potential not using adequate contraceptive methods * Participants with severe pulmonary dysfunction at screening, or evidence of pulmonary exacerbation (defined as an acute worsening of respiratory symptoms that result from a decline in lung function) * Cardiac disease by history or at screening that, in the Investigator's opinion, is likely to worsen overall performance of efficacy measures during the study * History of seizure disorder, neurologic disease, or neuromuscular disease other than RYR1-RM * History of chronic orthopedic issues, acute injury, or expected surgery during the study that may affect the ability to complete study assessments * Positive test results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) * 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) * History within the past year of alcohol or other drug substance abuse * Known hypersensitivity to the investigational product of related compounds * 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 the study drug * Treatment with sensitive or narrow therapeutic index CYP3A4 substrates within 7 days or 5 half-lives, whichever is longer, prior to first dose of the study drug * Treatment with strong or moderate CYP2C8 inhibitor or inducers within 7 days or 5 half-lives, whichever is longer, prior to the first dose of the study drug * Currently enrolled in another study or received treatment with any other investigational drug within 30 days or \> 5 half-lives, whichever is longer, prior to screening * Has reported any suicide ideation of Category 4 or 5 on the C-SSRS within 6 months prior to screening or any suicidal behavior in the last two years prior to screening as indicated by any 'yes' answers on the suicidal behavior section of the C-SSRS
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in the 1-minute sit-to-stand test (1-MSST) | Day 1 to day 28 [approximately] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the 6-Minute Walk Test (6-MNWT) | Day 1 to day 28 [approximately] | — |
| Change from baseline in the Timed Up and Go Test (TUG) | Day 1 to day 28 [approximately] | — |
| Change from baseline in the 4-Stair Climb Test (4-SCT) | Day 1 to day 28 [approximately] | — |
| Change from baseline Quantitative Muscle Assessment (QMA) | Day 1 to day 28 [approximately] | — |
| Change from baseline Manual Muscle Testing (MMT) | Day 1 to day 28 [approximately] | — |
| Change from baseline in Patient-Reported Outcomes Measurement Information System-fatigue (PROMIS-F) | Day 1 to day 28 [approximately] | — |
| Change from baseline in Patient-Reported Outcomes Measurement Information System-physical fatigue (PROMIS-PF) | Day 1 to day 28 [approximately] | — |
| Chage in International Physical Activity Questionnaire (IPAQ) | Day 1 to day 28 [approximately] | — |
| Number of Adverse Events | Day 1 to end of study [approximately 68 weeks] | — |
| Change from baseline in systolic blood pressure | Day 1 to end of study [approximately 68 weeks] | Systolic blood pressure will be measured in millimeters of mercury (mmHg) |
| Change from baseline in diastolic blood pressure | Day 1 to end of study [approximately 68 weeks] | Diastolic blood pressure will be measured in millimeters of mercury (mmHg) |
| Change from baseline in temperature | Day 1 to end of study [approximately 68 weeks] | Temperature will be measured in degrees Centigrade (°C) |
| Change from baseline in hemoglobin | Day 1 to end of study [approximately 68 weeks] | Hemoglobin concentration will be measured in grams per liter (g/L) using standard hematology laboratory methods |
| Change from baseline in white blood cell count | Day 1 to end of study [approximately 68 weeks] | White blood cell count will be measured in ×10⁹/L using standard hematology laboratory methods |
| Change from baseline in platelet count | Day 1 to end of study [approximately 68 weeks] | Platelet count will be measured in ×10⁹/L using standard hematology laboratory methods |
| Change from baseline in serum creatinine | Day 1 to end of study [approximately 68 weeks] | Serum creatinine will be measured in micromoles per liter (µmol/L) using standard clinical chemistry methods |
| Change from baseline in estimated glomerular filtration rate | Day 1 to end of study [approximately 68 weeks] | Estimated glomerular filtration rate (eGFR) will be calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation |
| Change from baseline in serum glucose | Day 1 to end of study [approximately 68 weeks] | Serum glucose concentration will be measured in millimoles per liter (mmol/L) using standard clinical chemistry methods |
| Change from baseline in QTc interval | Day 1 to end of study [approximately 68 weeks] | Corrected QT interval (QTcF) will be measured in milliseconds using triplicate 12-lead electrocardiograms |
| Change from baseline in urine protein | Day 1 to end of study [approximately 68 weeks] | Urine protein will be measured in milligrams per liter (mg/L) using standard urinalysis methods |
Countries
France, Germany, Netherlands, Spain, United Kingdom
Contacts
CONTACTPatrick Round
Outcome results
None listed