Catecholaminergic Polymorphic Ventricular Tachycardia Type 1Phase 2NCT05122975
Treatment of an Inherited Ventricular Arrhythmia
A Phase 2 study testing S48168 (ARM210) in people with Catecholaminergic Polymorphic Ventricular Tachycardia Type 1, run by RyCarma Therapeutics, Inc. at 2 sites in 2 countries.
Trial summary
The goal of the proposed project is to determine the safety and tolerability as well as the preliminary efficacy of a novel small molecule drug, S48168 (ARM210), for the treatment of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Catecholaminergic Polymorphic Ventricular Tachycardia Type 1
- What is being tested?
- S48168 (ARM210)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Aug 2023to 1 Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all the following conditions to be eligible for enrollment into the study:
- Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Participants who are willing and able to comply with scheduled visits, study drug administration plan, study restrictions, and study procedures.
- Participants have a confirmed genetic diagnosis of CPVT1 and supporting clinical phenotype, including residual ventricular ectopy (a complexity score ≥ 2; requiring at minimum the presence of PVCs in bigeminy on exercise stress test) on a stable (at least 1 month) standard-of-care, CPVT1-directed treatment regimen as decided by their CPVT treating physician.
- Have a body mass index (BMI) ≤ 36 kg/m2 (inclusive) at screening.
- Male participants agree to not donate sperm from the first day of dosing of study drug until 5 half-lives plus 90 days (approximately 94 days) after the last dose of study drug.
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- Female participants:
- eligible to participate if she is not pregnant or breastfeeding, and uses one of the following highly effective birth control methods (from the first dose until 5 half-lives plus 90 days (approximately 94 days):
- Prescribed hormonal oral contraceptives, vaginal ring, or transdermal patch.
- Intrauterine device (IUD).
- Intrauterine hormone-releasing system (IUS).
- Depot/implantable hormone (e.g., Depo-Provera®, Implanon).
- Bilateral tubal occlusion/ligation.
- Sexual abstinence.
- Refraining from heterosexual intercourse during the entire period of risk associated with the study requirements.
- If the participant decides to become sexually active during the study, then one of the highly effective birth control methods must be used.
- OR
- Is a woman of non-childbearing potential; defined by at least 1 of the following criteria:
- Postmenopausal defined as 12 months of spontaneous amenorrhea without a medical cause and follicle stimulating hormone (FSH) serum level > 40 mIU/mL without the use of hormonal supplementation. Appropriated documentation of FSH levels is required.
- Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure.
- Has a congenital condition resulting in no uterus.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
- Daily use of medicines and dietary supplements need to be approved by the PI and Sponsor, or a drug/supplement-dependent wash-out prior to inclusion.
Who cannot join
- The presence of any of the following conditions will exclude a participant from study enrollment:
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose of study drug.
- History or presence of hypersensitivity or idiosyncratic reaction to the study drug, related compounds, or inactive ingredients.
- ALT or AST levels three times above the upper limits of normal (ULN) at screening (isolated elevations of total bilirubin < 2 X ULN with direct bilirubin below the ULN will be included). A recheck for confirmation is allowed.
- History of documented, EEG-confirmed epileptic seizures.
- History of cancer (malignancy). Exceptions: (1) Subjects with adequately treated non-melanomatous carcinoma or carcinoma in situ of the cervix may participate in the trial; (2) Subjects with other malignancies who have been successfully treated > 10 years prior to the screening where in the judgment of the investigator has revealed no evidence of recurrence from the time of treatment through the time of the screening except those identified at the beginning of the exclusion criterion; or (3) Subjects who in the opinion of the investigator are highly unlikely to sustain a recurrence for the duration of the trial.
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- Currently has uncontrolled diabetes defined as HbA1c > 7% at screening visit or diabetic neuropathy.
- Estimated creatinine clearance < 40mL/minute at screening visit.
- Clinically significant abnormality on their screening and/or prior to first dosing resting ECG, other than hypertensive related, or heart failure (ejection fraction < 30%) or other clinically significant structural heart disease.
- History of myocardial infarction in the last five years, or evidence of congestive heart failure.
- Ongoing medical condition that is deemed by the PI to interfere with the conduct or assessments of the study or safety of the subject.
- Unable to refrain from or anticipates the use of:
- Any non-approved medicines (prescribed standard-of-care for CPVT is approved) and/or dietary supplements beginning 14 days prior to the first dose of study drug and throughout the study. Thyroid hormone replacement medication may be permitted if subject has been on same stable dose for the last 3 months prior to the first dose of study drug.
- Any drugs known to be significant inducers or inhibitors of CYP2C8 enzymes for 28 days prior to the first dose of study drug and throughout the study. Is currently taking any drug which raises gastric pH, including proton pump inhibitors or H2 antagonists. Antacids may be used if taken at night.
- Participation in clinical trials for other therapeutic investigational drugs simultaneously or within the 4 weeks prior to the first dose of study drug.
- Plasma donation within 7 days prior to the first dose of study drug.
- Donation of blood or significant blood loss within 56 days prior to the first dose of study drug.
- Is mentally or legally incapacitated at the time of screening visit.
- Is unable to take orally administered tablets.
- Is an immediate family member of the Sponsor or employee of the clinical site or may consent under duress.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Amsterdam University Medical Center
Amsterdam-Zuidoost, 91105
About this study
Official title: Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia Type 1 (CPVT1)
The goal of the proposed project is to determine the safety and tolerability as well as the preliminary efficacy of a novel small molecule drug, S48168 (ARM210), for the treatment of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1). This disease is associated with fatal changes in heart rhythms leading to sudden death with exercise or excessive excitement. It is due to mutations in the Ryanodine Receptor calcium release channel, which cause leaky channels leading to the disease. S48168 (ARM210) repairs these leaky channels and can be a disease-modifying therapy restoring normal function to the channels. This result would allow patients with CPVT to live normal, active lives. Funding Source- FDA OOPD.
- Being tested
- S48168 (ARM210), Matching Placebo
- Keywords
- Ventricular Arrhythmia, Calcium, Ryanodine Receptor 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S48168 (ARM210)Drug
Ryanodine Receptor modulator
Matching PlaceboDrug
Placebo of same size and consistency as S48168 (ARM210)
| Study group | Role | What they receive |
|---|---|---|
| S48168 (ARM210) once daily for 28 days | Experimental | Oral dose of S48168 (ARM210) once daily on top of standard of care regimen for 28 days. Receives: Drug: S48168 (ARM210) |
| Matching Placebo once daily for 28 days | Placebo comparator | Oral dose of placebo once daily on top of standard of care regimen for 28 days. Receives: Drug: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of S48168 (ARM210) treatment on the amount and complexity of exercise-• Change in ectopy score from baseline to Day 28 versus placebo (pre-dose Period 1 baseline to Day 28 Period 1 versus Day 28 Period 2
Analysis of ECG recordings during exercise testing examining for abnormal beats occurring with exercise, such as premature ventricular contractions (PVCs). The scale is as follows:
Ectopy Scoring Scale (0-4)
No ectopy 0
Isolated PVCs 1
Bigeminy 2
Couplets 3
Non-sustained VT 4
van der Werf, C., et al. (2011). "Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia." J Am Coll Cardiol 57(22): 2244-2254.
Measured: 28 days
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events
The number and severity of adverse events that can be related to treatment with S48168 (ARM210)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2021
- Study start1 Aug 2023
- Primary completion1 Apr 2024
- Study completion1 Apr 2024
Why it stopped: Due to challenges in recruiting patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Catecholaminergic Polymorphic Ventricular Tachycardia Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- RyCarma Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael J Ackerman, MD PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05122975
- Sponsor's protocol ID
- CL2-210-01
- Other IDs
- 1R01FD007279-01
- Status last verified
- Sep 2024
- First submitted
- 22 Oct 2021
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia Type 1 (CPVT1)
- ClinicalTrials.gov ID
- NCT05122975
- Acronym / sponsor ID
- CL2-210-01
- Keywords
- Ventricular Arrhythmia, Calcium, Ryanodine Receptor 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to challenges in recruiting patients.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- RyCarma Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 1 Apr 2024 (actual)
- Study completion
- 1 Apr 2024 (actual)
- First posted
- 17 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the proposed project is to determine the safety and tolerability as well as the preliminary efficacy of a novel small molecule drug, S48168 (ARM210), for the treatment of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1). This disease is associated with fatal changes in heart rhythms leading to sudden death with exercise or excessive excitement. It is due to mutations in the Ryanodine Receptor calcium release channel, which cause leaky channels leading to the disease. S48168 (ARM210) repairs these leaky channels and can be a disease-modifying therapy restoring normal function to the channels. This result would allow patients with CPVT to live normal, active lives. Funding Source- FDA OOPD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| S48168 (ARM210) once daily for 28 days | Experimental | Drug: S48168 (ARM210)Oral dose of S48168 (ARM210) once daily on top of standard of care regimen for 28 days. |
| Matching Placebo once daily for 28 days | Placebo comparator | Drug: Matching PlaceboOral dose of placebo once daily on top of standard of care regimen for 28 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participants must meet all the following conditions to be eligible for enrollment into the study:
- Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Participants who are willing and able to comply with scheduled visits, study drug administration plan, study restrictions, and study procedures.
- Participants have a confirmed genetic diagnosis of CPVT1 and supporting clinical phenotype, including residual ventricular ectopy (a complexity score ≥ 2; requiring at minimum the presence of PVCs in bigeminy on exercise stress test) on a stable (at least 1 month) standard-of-care, CPVT1-directed treatment regimen as decided by their CPVT treating physician.
- Have a body mass index (BMI) ≤ 36 kg/m2 (inclusive) at screening.
Key exclusion criteria (20 listed)
- The presence of any of the following conditions will exclude a participant from study enrollment:
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose of study drug.
- History or presence of hypersensitivity or idiosyncratic reaction to the study drug, related compounds, or inactive ingredients.
- ALT or AST levels three times above the upper limits of normal (ULN) at screening (isolated elevations of total bilirubin < 2 X ULN with direct bilirubin below the ULN will be included). A recheck for confirmation is allowed.
- History of documented, EEG-confirmed epileptic seizures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S48168 (ARM210)Ryanodine Receptor modulator | Drug | S48168 (ARM210) once daily for 28 days |
| Matching PlaceboPlacebo of same size and consistency as S48168 (ARM210) | Drug | Matching Placebo once daily for 28 days |
Primary outcome
The effect of S48168 (ARM210) treatment on the amount and complexity of exercise-• Change in ectopy score from baseline to Day 28 versus placebo (pre-dose Period 1 baseline to Day 28 Period 1 versus Day 28 Period 2
Time frame: 28 days
Analysis of ECG recordings during exercise testing examining for abnormal beats occurring with exercise, such as premature ventricular contractions (PVCs). The scale is as follows: Ectopy Scoring Scale (0-4) No ectopy 0 Isolated PVCs 1 Bigeminy 2 Couplets 3 Non-sustained VT 4 van der Werf, C., et al. (2011). "Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia." J Am Coll Cardiol 57(22): 2244-2254.
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 28 days
Results and safety
The study was stopped early (reason given: Due to challenges in recruiting patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael J Ackerman, MD PhD principal investigator
Mayo Clinic
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing S48168 (ARM210) in people with Catecholaminergic Polymorphic Ventricular Tachycardia Type 1, run by RyCarma Therapeutics, Inc. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to challenges in recruiting patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The effect of S48168 (ARM210) treatment on the amount and complexity of exercise-• Change in ectopy score from baseline to Day 28 versus placebo (pre-dose Period 1 baseline to Day 28 Period 1 versus Day 28 Period 2 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.