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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Milestone Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 May 2024 → ongoing

Decision date (initial)

2023-08-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Milestone Pharmaceuticals Inc.

External identifiers

EU CT number

2022-500319-38-00

ClinicalTrials.gov

NCT05763953

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To demonstrate the efficacy of a single intranasal (IN) dose of etripamil nasal spray (NS) in terminating a spontaneous episode of PSVT in
• Part 1: Patients aged 12 to <18 years, and
• Part 2: Patients aged 6 to <12 years.

Secondary objectives 1

1. To evaluate the safety and tolerability of etripamil nasal spray (NS) in Patients aged 12 to <18 years (Part 1) and Patients aged 6 to <12 years (Part 2)

Conditions and MedDRA coding

Paroxysmal supraventricular tachycardia (PSVT)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002303-PIP01-17

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female patients: a) Part 1: patients 12 to <18 years of age b) Part 2: patients 6 to <12 years of age
2. Body mass index (BMI) between the 5th and the 85th percentiles interpreted relative sex and age
3. 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
4. Signed written informed consent/assent obtained
5. 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.
6. Willing and able to comply with study procedures.

Exclusion criteria 8

1. 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).
2. 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
3. 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
4. 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.
5. Known hypersensitivity to verapamil or to any of the excipients of the study drug
6. 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
7. History of hyperthyroidism
8. Current pregnancy or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy: The percentage of patients converting to SR in the first 15 minutes after administration of etripamil NS. A successful conversion is defined as conversion of PSVT to SR that is maintained for at least 30 seconds.

Secondary endpoints 5

1. Time to termination of the PSVT episode and conversion to sinus rhythm (SR)
2. Percentage of patients requiring additional medical intervention treatment for the PSVT episode in the first 15 minutes after study drug administration
3. Frequency of AEs
4. Local (administration site) tolerability
5. Post-dose changes in vital signs (HR and BP)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Milestone Pharmaceuticals Inc.

Sponsor organisation

Milestone Pharmaceuticals Inc.

Address

420-1111 Dr.-Frederik-Philips Blvd

City

Saint-Laurent

Postcode

H4M 2X6

Country

Canada

Scientific contact point

Organisation

Milestone Pharmaceuticals Inc.

Contact name

Information Point

Public contact point

Organisation

Milestone Pharmaceuticals Inc.

Contact name

Information Point

Third parties 3

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications