The NODE-202 Study (Study of Etripamil Nasal Spray in Pediatric Patients)

Last updated: August 8, 2024
Sponsor: Milestone Pharmaceuticals Inc.
Overall Status: Active - Recruiting

Phase

2

Condition

Cardiac Disease

Dysrhythmia

Heart Defect

Treatment

Etripamil NS

Clinical Study ID

NCT05763953
MSP-2017-1265
  • Ages 6-17
  • All Genders

Study Summary

NODE-202 is a Phase 2, multicenter, multinational, single dose, open-label, 2-part, sequential design study in pediatric patients with an established diagnosis of paroxysmal supraventricular tachycardia (PSVT) presenting with a symptomatic episode of PSVT.

In Part 1, at least 30 patients aged 12 to <18 years will be enrolled and treated with etripamil nasal spray (NS). Efficacy, safety, tolerability and PK (for at least 12 patients) will be assessed after administration of 70 mg etripamil NS (Part 1A). At least 18 subsequent patients will be enrolled and treated with the etripamil NS with the dose determined by the Pharmacokinetic (PK) analysis and will undergo efficacy and safety/tolerability assessments (Part 1B).

In Part 2, at least 30 patients aged 6 to <12 years will be enrolled and treated with etripamil NS at a dose selected based on appropriate body size-based modeling, as well as efficacy, safety/tolerability, and PK data collected in Part 1. Efficacy, safety, tolerability and PK (for at least 12 patients) will be assessed after administration of etripamil NS (Part 2A). At least 18 subsequent patients will be enrolled and treated with the etripamil NS with the dose determined by the PK analysis and will undergo efficacy and safety/tolerability assessments (Part 2B).

The study will include the following visits: A Screening Visit, A Treatment Visit, , and A Follow-Up/End of Study Visit.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Patients will be eligible for study participation if they meet all of the following criteria at screening:

  1. Male or female patients

  2. Part 1: patients 12 to <18 years of age

  3. Part 2: patients 6 to <12 years of age

  4. Body mass index (BMI) between the 5th and the 85th percentiles interpreted relativesex and age

  5. History of PSVT documented by ECG or other monitoring modality (e.g., Holtermonitor, event recorder) showing SVT involving the Atrioventricular (AV) node (i.e.,Atrioventricular nodal reentry tachycardia (AVNRT) or Atrioventricular reentranttachycardia (AVRT)). If patient had a prior ablation for PSVT, patient must havedocumented evidence of PSVT post-ablation

  6. Signed written informed consent/assent obtained

  7. Per Investigator's decision, females of childbearing potential (defined as any womanor adolescent who has begun menstruation) must additionally satisfy the followingcriteria:

  8. Negative pregnancy test at screening

  9. Adequate contraception, unless total abstinence is used

  10. Willing and able to comply with study procedures.

Exclusion

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

  1. History or presence of any of the following at the screening visit:

  2. Patients with a history of atrial arrhythmia that does not involve the AV nodeas part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter,atrial tachycardia) are not eligible

  3. Permanent junctional reciprocating tachycardia

  4. Ventricular pre-excitation (e.g., delta wave on ECG, Wolff Parkinson Whitesyndrome)

  5. Second- or third-degree AV block

  6. Sick sinus syndrome or clinically significant bradycardia (<50 bpm orequivalent in this patient population) on the resting ECG

  7. Ventricular tachycardia

  8. Long QT syndrome

  9. Major structural heart disease (e.g., Ebstein's anomaly, corrected congenitalheart disease) or symptoms of congestive heart failure (New York HeartAssociation class II to IV).

  10. Evidence of impaired liver function (alanine aminotransferase [ALT] and/or aspartateaminotransferase [AST] >3 x upper limit of normal for age and gender) at theScreening Visit

  11. Evidence of End-Stage Renal Disease as determined by an estimated glomerularfiltration rate assessed at the Screening Visit of <15 mL/min/1.73m2, or requiringhemodialysis;

  12. Treatment with any of the following that cannot or will not be discontinued duringstudy participation:

  13. Any investigational drug within 60 days prior to study drug administration

  14. IV beta-adrenergic blocking drugs (e.g., propranolol, esmolol), calcium channelblocking drugs (e.g., verapamil, diltiazem) or amiodarone within 24 hours priorto study drug administration

  15. Oral amiodarone within 30 days prior to study drug administration

  16. Class I or III antiarrhythmic agents (e.g., flecainide, propafenone, sotalol)within five half-lives prior to study drug administration

  17. Any other drug that has a contraindication with verapamil

  18. Known hypersensitivity to verapamil or to any of the excipients of the study drug

  19. Any other significant co-morbid condition that may have a negative impact on thepatient's participation in the study or likely to result in non-compliance

  20. History of hyperthyroidism

  21. Current pregnancy or breastfeeding

Study Design

Total Participants: 60
Treatment Group(s): 1
Primary Treatment: Etripamil NS
Phase: 2
Study Start date:
December 11, 2023
Estimated Completion Date:
June 30, 2027

Study Description

NODE-202 is a Phase 2, multicenter, multinational, single-dose, open-label, 2-part, sequential design study of pediatric patients with an established diagnosis of PSVT presenting with a sustained, symptomatic episode of PSVT.

At least 60 evaluable patients administered etripamil NS are estimated as an adequate population to inform on the efficacy and safety of etripamil NS in pediatric patients (aged 6 to <18 years) with PSVT. Patients will be enrolled according to the following sequential design:

Part 1: At least 30 patients aged 12 to <18 years will be treated with 70 mg etripamil NS for a PSVT episode. Efficacy, safety, tolerability and PK (at least for 12 patients) will be assessed after administration of etripamil.

Part 1A: at least 12 patients will undergo efficacy, safety/tolerability, and PK assessments. The data safety monitoring committee (DSMC) will complete an interim assessment of safety, tolerability; if the Sponsor decides to increase the dose above 70 mg for the remaining 18 patients, the Pediatric Committee (PDCO) and the Food and Drug Administration (FDA) will complete an interim assessment of efficacy, safety, tolerability, and PK data before additional patients in this age group can be treated with etripamil at the same or a modified dose level.

Part 1B: at least 18 subsequent patients will be treated with etripamil NS with the dose determined based on Part 1A data analysis and will undergo efficacy and safety/tolerability assessments.

Part 2: Clinical assessments in at least 30 patients aged 6 to <12 years will only be undertaken if, after a comprehensive review of safety, tolerability, efficacy, and PK data collected in patients aged 12 to <18 years, confirms a positive benefit-risk ratio in that age group, sufficient to permit administration of etripamil NS in the younger age group. The initial dose for Part 2 will be selected based on appropriate body size-based modelling, as well as safety/tolerability, and efficacy data collected in Part 1.

Part 2A: at least 12 patients will undergo efficacy, safety/tolerability, and PK assessments. The DSMC will complete an interim assessment of safety, tolerability; the PDCO and FDA will complete an interim assessment of safety, tolerability, and PK data before additional patients in this age group can be treated with etripamil at the same or a modified dose level.

Part 2B: at least 18 subsequent patients will be enrolled and treated with etripamil NS with the dose determined based on Part 2A data analysis and will undergo efficacy and safety/tolerability assessments.

The study will include:

A Screening Visit during which the Investigator will verify that the patient currently meets the eligibility criteria of the NODE-202 study, will obtain the Informed Consent/Assent, will evaluate the patient's medical status and concomitant medications, will perform a 12-Lead ECG using provided study-specific equipment, will take blood and urine for clinical laboratory evaluations (local laboratory) and will assess the patient's eligibility according to the inclusion/exclusion criteria. Also, qualified patients will be instructed that as soon as they have identified symptoms they consider being consistent with PSVT, they must attend the Study Medical Facility assigned by their Investigator for a treatment visit.

A Treatment Visit during which patients will arrive at the Study Medical Facility with symptoms consistent with PSVT, and the following actions will be performed: confirmation of eligibility, evaluation of vital signs and initiation of a 12-lead Electrocardiogram (ECG) using the provided ECG equipment. If after ECG assessment diagnosis of PSVT is not confirmed, the patient must not be administered etripamil NS and will receive standard of care treatment based on the diagnosis. If ECG assessment confirms the presence of PSVT, a vagal maneuver (VM) will be performed by the patient or physician, based on the Investigator's judgement. If the VM is not successful in terminating the confirmed PSVT episode, etripamil NS will then be administered intranasally by study site personnel, under medical supervision and ECG monitoring for 1 hour.

A Follow-Up/End of Study Visit (1 to 5 days after an episode) during which any Adverse Events (AEs) and ECG will be recorded, and vital signs will be measured.

Connect with a study center

  • The University of British Columbia

    Vancouver, V6H3V4
    Canada

    Site Not Available

  • Universitätsmedizin Göttingen, Klinik für Pädiatrische Kardiologie, Intensivmedizin und Neonatologie

    Göttingen, 37075
    Germany

    Active - Recruiting

  • Hospital Sant Joan de Déu

    Barcelona, 08950
    Spain

    Site Not Available

  • Hospital Infantil Universitario La Paz

    Madrid, 28046
    Spain

    Active - Recruiting

  • Phoenix Children's Hospital

    Phoenix, Arizona 85016
    United States

    Active - Recruiting

  • Advocate Children's Hospital

    Oak Lawn, Illinois 60453
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Site Not Available

  • Oregon Health and Science University

    Portland, Oregon 97239
    United States

    Active - Recruiting

  • Le Bonheur Children's Hospital

    Memphis, Tennessee 38103
    United States

    Active - Recruiting

  • Baylor College of Medicine

    Houston, Texas 77030
    United States

    Site Not Available

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