A Phase 2 Study of CRD-4730 in CPVT

Phase 2

Not yet recruiting

Conditions: Catecholaminergic Polymorphic Ventricular Tachycardia

Registration Number: 2024-515564-32-00

Lead Sponsor: Cardurion Pharmaceuticals Inc.

Brief Summary: To assess the safety and tolerability of CRD-4730 when administered to participants with catecholaminergic polymorphic ventricular tachycardia (CPVT) following repeated dose administration

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

The participant is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
The participant is male or female, ≥18 years of age and of legal adult age in accordance with local requirements.
The participant is considered by the Investigator to be in good general health, aside from their CPVT diagnosis, as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at Screening.
The participant has a confirmed CPVT diagnosis, based on genetic screening for a pathogenic ryanodine receptor (RYR2) mutation and a clinical phenotype consistent with CPVT at Screening. Previous CPVT genetic testing documented in medical history is acceptable if confirmed by the Investigator and documented in the study source records.
The participant can perform an EST during which frequent premature ventricular contractions (PVCs; ≥10 per minute), ventricular bigeminy, or higher-grade VA (equivalent to a VA score ≥2) are identified by the Investigator. Please refer to the complete VA scoring system in the full protocol
The participant has been on a stable dose of at least 1 antiarrhythmic medication (including beta blockers but not amiodarone) for 4 weeks prior to Screening, unless the participant has been unable to tolerate antiarrhythmic therapy previously
Female participants must meet at least 1 of the following criteria: a. Is postmenopausal (defined as amenorrhea for 12 consecutive months and follicle stimulating hormone (FSH) >40 mIU/mL before first dose of study drug) for at least 1 year before screening visit. b. Is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy). c. Agrees to practice 1 highly effective method of birth control AND 1 additional effective (barrier) method of contraception at the same time until 5 half-lives (approximately 3 days) plus the estimated period of 1 menstruation cycle, defined as 30 days (33 days total), after the last dose of study drug. d. Has a sterilized male partner (defined as having had a bilateral orchidectomy), if the partner is the sole sexual partner. e. Agrees to practice true abstinence. Additionally, females who are women of childbearing potential (WOCBP) must not donate ova from Screening until 30 days plus 5 half-lives (33 days total) after the last dose of study drug. A female is considered a WOCBP (ie, fertile) following menarche and until becoming postmenopausal, unless permanently sterile as defined in Inclusion Criterion 7b.
Male participants must meet at least 1 of the following criteria: a. Is sterilized (defined as having had a bilateral orchidectomy) and agrees to use a male condom from Screening until 5 half-lives (3 days total) after the last dose of study drug. b. Agrees to all of the following: i. Male participants with a WOCBP partner must agree to use a male condom (with or without a spermicidal agent) from Screening until 90 days (the estimated time period of the spermatogenesis cycle) plus 5 half-lives (93 days total) after the last dose of study drug; additionally, a WOCBP partner should use a highly effective method during this same time period. ii. Male participants with a partner who cannot become pregnant (a woman who is not a WOCBP or a male partner) must agree to use a male condom during sexual intercourse from Screening until 5 half-lives (3 days total) after the last dose of study drug. iii. Male participants must agree not to donate sperm from the first study drug administration until 90 days plus 5 half-lives (93 days total) after the last dose of study drug. c. Agrees to practice true abstinenceand agrees not to donate sperm from the first dose of study drug until 93 days after the last dose of study drug..

Exclusion Criteria

The participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the participant’s ability to participate in the study.
The participant has hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × (upper limit of normal [ULN]) and/or total bilirubin >1.5 × ULN at Screening (unless secondary to confirmed Gilbert syndrome).
The participant has any clinically significant illness, in the opinion of the Investigator, occurring within 28 days prior to the Screening visit (window: Day -21 to Day -1) and up to the first day of study drug administration (Day 1).
The participant has acute or chronic hepatitis B (HBV; defined as hepatitis B surface antigen [HBsAg] reactive), acute or chronic hepatitis C virus (HCV; defined as detection of HCV antibody and RNA [qualitative]), or human immunodeficiency virus (HIV) infection. Note: Participants who have been effectively treated for and cleared/cured of hepatitis B or hepatitis C are eligible for enrollment. Participants must be negative for HBsAg and HCV RNA (if positive for HCV antibody; otherwise, a negative HCV antibody alone is sufficient).
The female participant is pregnant, lactating/breastfeeding, or has plans to become pregnant during the study or within 3 months following the last study drug administration.
The participant has participated in a previous clinical study and received investigational product within 30 days of dosing or 5 drug half-lives, whichever is longer.
The participant has taken any antiarrhythmic drug in addition to their stable, chronic regimen unless it has been at least 5 half-lives since administration at the time of Screening.
For participants who have received the COVID-19 vaccine, the most recent vaccine dose must be at least 14 days before the first dose of study drug.
The participant has taken amiodarone within 3 months prior to Screening.
The participant has taken strong inhibitors of cytochrome P450 (CYP)3A4 and P-glycoprotein within 14 days prior to the first dose of study drug.
The participant has a history of relevant drug and/or food allergies or who experiences a serious hypersensitivity reaction, including anaphylaxis, to CRD-4730 or any of its excipients.
The participant has any acute or chronic illness, aside from their CPVT diagnosis, which, in the opinion of the Investigator, may place the participant at risk because of participation in the study.
The participant has a history of alcohol, cannabis, or drug (other than caffeine) use disorder, in the opinion of the Investigator, within 12 months prior to Screening.
The participant has any other issues which, in the opinion of the Investigator, will make the participant ineligible for study participation.
The participant is an employee of the Sponsor, including employees contracted by the Sponsor (ie, consultants), an employee of the contract research organization (CRO), or an employee of the study site.
Additional eligibility that applies to French participants: • Participants in France should not be deprived of their liberty by a judicial or administrative decision as per Art L 1121-6 of Code de la Santé Publique. • Participants in France should not be undergoing psychiatric care by virtue of a court order or an administrative order as per Art L 1121-6 of Code de la Santé Publique. • Participants in France should not be under legal protection or unable to give their consent as per Art L 1121-8 of Code de la Santé Publique. • Participants in France should be affiliated to a Social Security Scheme or be a beneficiary of one as per Art L1121-8-1 of Code de la Santé Publique.
The participant has clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease.
The participant has a clinically significant abnormal ECG not explained by the diagnosis of CPVT at Screening (for example, clinically significant abnormal morphology consistent with an alternate diagnosis such as Brugada syndrome or arrhythmogenic right ventricular cardiomyopathy, or clinically significant abnormal intervals, such as prolonged QT in long QT syndrome).
The participant has a history of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of Screening.
The participant undergoes implantable cardioverter-defibrillator (ICD) implantation or has sympathetic nerve denervation within 3 months of Screening.
The participant has an anticipated change in exercise regimen or new exercise program during the course of the study.
The participant has a history of malignancy within the past 5 years at Screening, with the exception of successfully treated basal cell carcinoma or nonmetastatic squamous cell carcinoma of the skin or cervical carcinoma in situ. Prior exposure to chest radiation for any malignancy is exclusionary.
The participant has abnormal blood pressure, defined as supine symptomatic hypotension, systolic blood pressure >150 mm Hg or diastolic blood pressure >90 mm Hg, or symptomatic bradycardia or a heart rate >100 bpm at Screening and/or on Day 1. Blood pressure and pulse should be measured after the participant has been in the seated position after 5 minutes of rest.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
The number and severity of treatment-emergent adverse events (TEAEs) related to study drug treatment		The number and severity of treatment-emergent adverse events (TEAEs) related to study drug treatment

Secondary Outcome Measures

Name	Time	Method
Change in VA score during EST from baseline to Day {CCI}, from baseline to Day {CCI}, and from baseline to Day {CCI}		Change in VA score during EST from baseline to Day {CCI}, from baseline to Day {CCI}, and from baseline to Day {CCI}
Plasma concentrations of CRD-4730 over time for each treatment period		Plasma concentrations of CRD-4730 over time for each treatment period

Trial Locations

Locations (6): Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb
🇮🇹
Pavia, Italy
Hospital Sant Joan De Deu Barcelona
🇪🇸
Esplugues De Llobregat, Spain
Amsterdam UMC Stichting
🇳🇱
Amsterdam, Netherlands
Centre Hospitalier Universitaire De Nantes
🇫🇷
Saint Herblain, France
Assistance Publique Hopitaux De Paris
🇫🇷
Paris Cedex 18, France
Hospices Civils De Lyon
🇫🇷
Bron, France
Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb
🇮🇹Pavia, Italy
Silvia Giuliana Maria Luigina PRIORI
Site contact
+390382592774
silvia.priori@icsmaugeri.it