The NODE-202 Study Multi-Center, Multi-National, Open-Label, Efficacy and Safety Study of Etripamil Nasal Spray in Pediatric Patients with Paroxysmal Supraventricular Tachycardia
- Trial ID
- 2022-500319-38-00
- Protocol
- MSP-2017-1265
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to demonstrate the **efficacy** of a single intranasal dose of etripamil nasal spray in terminating a spontaneous episode of **paroxysmal supraventricular tachycardia (PSVT)**. This is evaluated in two distinct pediatric cohorts: patients aged 12 to less than 18 years, and patients aged 6 to less than 12 years. The clinical relevance of this objective lies in providing a rapid, non-invasive treatment option for PSVT, which is crucial for managing acute episodes and improving patient outcomes in the pediatric population.
Secondary objectives include evaluating the **safety** and **tolerability** of etripamil nasal spray in the same age groups. This assessment is essential to ensure that the treatment is not only effective but also safe for use in children, thereby supporting its potential adoption in clinical practice for managing PSVT in younger patients.
Participants
The clinical trial involves a total of **30 participants** diagnosed with **paroxysmal supraventricular tachycardia (PSVT)**. The study population is divided into two parts: Part 1 includes patients aged 12 to less than 18 years, and Part 2 includes patients aged 6 to less than 12 years. Both male and female subjects are included, with a body mass index (BMI) between the 5th and the 85th percentiles, adjusted for sex and age. Participants were selected based on a documented history of PSVT, confirmed by ECG or other monitoring modalities. The trial does not involve a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified. The study aims to evaluate the efficacy of a single intranasal dose of etripamil nasal spray in terminating a spontaneous episode of PSVT.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of **Etripamil** nasal spray in pediatric patients with **paroxysmal supraventricular tachycardia (PSVT)**. This is a multi-center, multi-national, open-label study conducted in two parts, targeting patients aged 6 to <18 years. The trial is structured as a Phase 4 study, with the primary objective of demonstrating the efficacy of a single intranasal dose of Etripamil in terminating a spontaneous episode of PSVT. The trial is expected to commence recruitment on June 30, 2023, and conclude by June 30, 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, body mass index, and documented history of PSVT. Following successful screening, participants will receive the study drug during a treatment visit, where the primary endpoint will be the percentage of patients converting to sinus rhythm (SR) within 15 minutes post-administration. Secondary endpoints include time to termination of the PSVT episode, the need for additional medical intervention, and the frequency of adverse events.
Follow-up visits will be conducted to monitor the participants' health status, assess local tolerability at the administration site, and evaluate post-dose changes in vital signs such as heart rate and blood pressure. The end-of-study visit will mark the conclusion of the participant's involvement, which is anticipated to last for a maximum of one day, given the acute nature of the treatment. Conditions that may lead to early termination from the study include non-compliance with study procedures or the occurrence of significant adverse events.
Treatment
The clinical trial involves the administration of **Etripamil**, a **nasal spray** formulation developed by Milestone Pharmaceuticals Inc. Etripamil is a chemical compound designed for the treatment of **paroxysmal supraventricular tachycardia (PSVT)**. The pharmaceutical form of Etripamil is a nasal spray, and it is administered intranasally. The delivery system is a bidose nasal spray device, which is a single-use, dual spray system. It is engineered to deliver a total of 200 µL of drug solution, divided into two 100 µL spray deployments. The device comprises a container, container holder, actuator, and plunger, with the drug formulation stored in contact with a glass container and rubber plunger. During actuation, the drug is also in temporary contact with a stainless steel cannula. The maximum daily dose and total dose amount for Etripamil is 70 mg, with a maximum treatment period of one day.
In this study, Etripamil is the sole experimental medication, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed to assess the efficacy of a single intranasal dose of Etripamil in terminating spontaneous episodes of PSVT in pediatric patients. Participant compliance with the dosing schedule is monitored through the use of the single-use nasal spray device, ensuring accurate administration of the medication. The trial does not include any additional non-experimental treatments or interventions.
Efficacy
Efficacy in the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of **Paroxysmal Supraventricular Tachycardia (PSVT)** using Etripamil nasal spray. The primary endpoint is the percentage of patients converting to sinus rhythm (SR) within the first 15 minutes after administration of the nasal spray. A successful conversion is defined as the conversion of PSVT to SR that is maintained for at least 30 seconds.
Secondary endpoints include the time to termination of the PSVT episode and conversion to SR, the percentage of patients requiring additional medical intervention within the first 15 minutes post-administration, the frequency of adverse events (AEs), local tolerability at the administration site, and post-dose changes in vital signs such as heart rate (HR) and blood pressure (BP). These parameters will be measured and collected at specified timepoints to ensure comprehensive analysis of the treatment's efficacy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patients: a) Part 1: patients 12 to <18 years of age b) Part 2: patients 6 to <12 years of age
- Body mass index (BMI) between the 5th and the 85th percentiles interpreted relative sex and age
- History of PSVT documented by ECG or other monitoring modality (e.g., Holter monitor, event recorder) showing SVT involving the AV node (i.e., AVNRT or AVRT). If patient had a prior ablation for PSVT, patient must have documented evidence of PSVT post-ablation
- Signed written informed consent/assent obtained
- Females of childbearing potential (defined as any woman or adolescent who has begun menstruation) must additionally satisfy the following criteria: a) Negative pregnancy test at screening b) Adequate contraception, unless total abstinence is used. Adequate contraception must be used from the time of signed informed consent until the post-treatment follow-up visit. Acceptable methods include combined (estrogen and progestogen containing) or progestogen-only hormonal contraception, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide. NOTE: Patients who become a female of child-bearing potential after their screening visit must be re-assessed for these criteria before a treatment visit.
- Willing and able to comply with study procedures.
Exclusion Criteria
- History or presence of any of the following at the screening visit: a) Patients with a history of atrial arrhythmia that does not involve the AV node as part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter, atrial tachycardia) are not eligible; b) Permanent junctional reciprocating tachycardia; c) Ventricular pre-excitation (e.g., delta wave on ECG, Wolff Parkinson White syndrome); d) Second- or third-degree AV block; e) Sick sinus syndrome or clinically significant bradycardia (<50 bpm or equivalent in this patient population) on the resting ECG; f) Ventricular tachycardia; g) Long QT syndrome; h) Major structural heart disease (e.g., Ebstein’s anomaly, corrected congenital heart disease) or symptoms of congestive heart failure (New York Heart Association class II to IV).
- Evidence of impaired liver function (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] >3 x upper limit of normal for age and gender) at the Screening Visit
- Evidence of End-Stage Renal Disease as determined by an estimated glomerular filtration rate assessed at the Screening Visit (using revised bedside Schwartz equation) of <15 mL/min/1.73m2, or requiring hemodialysis
- Treatment with any of the following that cannot or will not be discontinued during study participation: a) Any investigational drug within 60 days prior to study drug administration; b) IV beta-adrenergic blocking drugs (e.g., propranolol, esmolol), calcium channel blocking drugs (e.g., verapamil, diltiazem) or amiodarone within 24 hours prior to study drug administration; c) Oral amiodarone within 30 days prior to study drug administration; d) Class I or III antiarrhythmic agents (e.g., flecainide, propafenone, sotalol) within five half-lives prior to study drug administration; e) Any other drug that has a contraindication with verapamil.
- Known hypersensitivity to verapamil or to any of the excipients of the study drug
- Any other significant co-morbid condition that may have a negative impact on the patient’s participation in the study or likely to result in non-compliance
- History of hyperthyroidism
- Current pregnancy or breastfeeding
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 30 Jun 2023 | 5 |
 The Netherlands | Not Yet Recruiting | 30 Jun 2023 | — |
 Spain | Recruiting | 30 Jun 2023 | 20 |
| Netherlands | — | — | 5 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Etripamil | Test | NASAL SPRAY | INTRANASAL USE | 70 | 1 | PRD7711636 |