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NCT04141670

S 48168 (ARM 210) for the Treatment of RYR1-related Myopathies (RYR1-RM)

Completed Phase 1 Results posted Last updated 22 August 2024
What this trial tests

Phase 1 trial testing S48168 in RYR-1 Myopathy in 7 participants. Completed in 30 July 2023.

Timeline
25 August 2020
Primary endpoint
30 December 2022
30 July 2023

Quick facts

Lead sponsorRyCarma Therapeutics, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment7
Start date25 August 2020
Primary completion30 December 2022
Estimated completion30 July 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

RyCarma Therapeutics, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with RYR-1 Myopathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing Adverse Events When Treated With S48168 (ARM210) Primary · 42 days

Composite safety and tolerability profile of S48168 (ARM210) based on adverse event reporting

Participants with fatal adverse events (all cause mortality)
GroupValue95% CI
Low Dose Group0
High Dose Group0
Participants with serious adverse events
GroupValue95% CI
Low Dose Group0
High Dose Group0
Participants with non-serious adverse events
GroupValue95% CI
Low Dose Group3
High Dose Group3

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately two months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Low Dose Group
Serious: 0/3 (0%)
Deaths: 0/3
High Dose Group
Serious: 0/4 (0%)
Deaths: 0/4
Other adverse events (18 terms — click to expand)

ReactionSystemLow Dose GroupHigh Dose Group
HeadacheNervous system disorders
EosinophiliaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
VomitingGastrointestinal disorders
Procedural painInjury, poisoning and procedural complications
Skin lacerationInjury, poisoning and procedural complications
Blood creatine phosphokinase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Sinus headacheNervous system disorders
HaematuriaRenal and urinary disorders
Mechanical utricariaSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders

Data from ClinicalTrials.gov NCT04141670 adverse events section.

Sponsor's own description

This study proposes to test S 48168 (ARM210) in a Phase 1 trial in RYR1-RM patients, specifically. The objectives of this study are to explore the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD)/target engagement (TE) of S 48168 (ARM210), as well as effects on muscle/motor function, and fatigue in RYR1-RM patients. The study population will include adult patients (≥18 years of age) who have demonstrated leaky RyR1 channels that are responsive to S48168 (ARM210) ex vivo.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target.
    Dridi H, Kushnir A, Zalk R, Yuan Q, et al · · 2020 · cited 164× · PMID 32555383 · DOI 10.1038/s41569-020-0394-8
  2. Sarcopenia and Muscle Aging: A Brief Overview.
    Dao T, Green AE, Kim YA, Bae SJ, et al · · 2020 · cited 156× · PMID 33397034 · DOI 10.3803/enm.2020.405
  3. Alzheimer's-like signaling in brains of COVID-19 patients.
    Reiken S, Sittenfeld L, Dridi H, Liu Y, et al · · 2022 · cited 137× · PMID 35112786 · DOI 10.1002/alz.12558
  4. Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature.
    Lawal TA, Todd JJ, Witherspoon JW, Bönnemann CG, et al · · 2020 · cited 75× · PMID 33190635 · DOI 10.1186/s13395-020-00243-4
  5. Intracellular calcium leak as a therapeutic target for RYR1-related myopathies.
    Kushnir A, Todd JJ, Witherspoon JW, Yuan Q, et al · · 2020 · cited 51× · PMID 32236737 · DOI 10.1007/s00401-020-02150-w
  6. Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.
    Dridi H, Santulli G, Bahlouli L, Miotto MC, et al · · 2023 · cited 41× · PMID 37759809 · DOI 10.3390/biom13091409
  7. Ryanodine receptor remodeling in cardiomyopathy and muscular dystrophy caused by lamin A/C gene mutation.
    Dridi H, Wu W, Reiken SR, Ofer RM, et al · · 2021 · cited 26× · PMID 33388782 · DOI 10.1093/hmg/ddaa278
  8. Rycal S48168 (ARM210) for <i>RYR1</i>-related myopathies: a phase one, open-label, dose-escalation trial.
    Todd JJ, Lawal TA, Chrismer IC, Kokkinis A, et al · · 2024 · cited 16× · PMID 38318125 · DOI 10.1016/j.eclinm.2024.102433

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