NTC-801F, Selective IKACh Channel Blocker, in Patients with Hereditary Bradyarrhythmia due to KACh Channelopathy: An Investigator-Initiated Open-Label, Single-Arm, Phase II Clinical Trial

JRCT ID: jRCT2051200061

Registered date:05/10/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Patients with hereditary bradyarrhythmia due to KACh channelopathy
• Date of first enrollment: 06/01/2021
• Target sample size: 4
• Study type: Interventional
• Intervention(s): The study drug administration period will be 24 weeks. The dose regime of NTC-801F will be one NTC-801F tablet (containing 20 mg per tablet) administered 3 times per day.

Outcome(s)

Primary Outcome

<Efficacy>
1) In the case of patients without pacemaker implantation:
Reduction in the number of pauses of 2 seconds or more from baseline in 3-day Holter (72 hours) ECG at 24 weeks after administration of NTC-801F
2) In the case of patients with pacemaker implantation:
Decrease in pacing percentage from baseline in 3-day Holter ECG at 24 weeks after administration of NTC-801F (evaluate pacing percentage in atrium and/or ventricle based on the pacemaker setting mode)

Secondary Outcome

<Efficacy>
Changes from baseline are evaluated for the following parameters.
In all cases:
1) Improvement of Minnesota Heart Failure QOL Questionnaire at 24 weeks after administration
2) Rate of change in exercise tolerance indices* in cardiopulmonary exercise test (CPX) at 24 weeks after administration
*Exercise tolerance indices: maximum oxygen uptake: peak VO2, anaerobic threshold (AT), maximum load: peak work rate, carbon dioxide ventilation equivalent: VE/VCO2
3) Percentage change in the 6-minute walk test at 24 weeks after administration
4) Change trends in BNP value
5) Change trends in heart rate in a 12-lead ECG at rest
6) Increase in heart rate (total heart rate and average heart rate) on 3-day Holter ECG at 12 and 24 weeks after administration
7) Increase in maximum heart rate on 3-day Holter ECG at 12 and 24 weeks after administration
8) (In the case of atrial fibrillation) Increase in the number and total duration of sinus rhythms confirmed by 3-day Holter ECG at 12 and 24 weeks after administration
9) (In the case of sick sinus syndrome) Decrease in the number of atrial fibrillation episodes and in total duration of atrial fibrillation, and decrease in the number of episodes of supraventricular premature beats and atrioventricular block in 3-day Holter ECG at 12 and 24 weeks after administration

In the case of patients without pacemaker implantation:
10) Decrease in the number of pauses of 2 seconds or more in 3-day Holter ECG at 12 weeks after administration
11) Decrease in the number of pauses of 3 seconds or more in 3-day Holter ECG at 12 and 24 weeks after administration
12) Increase in minimum heart rate and decrease in maximum R-R interval on 3-day Holter ECG at 12 and 24 weeks after administration

In the case of patients with pacemaker implantation:
13) Decrease in pacing percentage in 3-day Holter ECG at 12 weeks after administration (evaluation of the pacing percentage of atrium and/or ventricle based on the pacemaker setting mode)
14) Decrease in the pacing percentage at the pacemaker check at 2, 4, 8, 12, 16, and 24 weeks after administration (evaluation of the pacing percentage in atrium and/or ventricle based on the pacemaker setting mode)

<Safety>
In all cases, the following parameters will be recorded.
1) Incidence of adverse events and side effects during the study period
2) Change trends in eGFR values at each visit
3) QT/QTc interval in 12-lead ECG at each visit
4) Frequency of ventricular arrhythmia on 3-day Holter ECG

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

Patients who meet all of the following conditions will be included.
1) Patients who have given written informed consent to participate in the trial.
2) Patients aged between 18 and 80 years old at the time of obtaining informed consent.
3) Patients diagnosed with KACh channelopathy according to screening and diagnostic procedures before obtaining informed consent.
4) Patients with preserved liver and renal functions at screening as follows:
(i) AST: <=3 times the upper limit of the normal institutional reference value
(ii) ALT: <=3 times the upper limit of the normal institutional reference value
(iii) Total bilirubin: less than twice the upper limit of the normal institutional reference value
(iv) Serum creatinine: less than twice the upper limit of the normal institutional reference value or eGFR: 30 mL/min/1.73 m2
5) In the case of women who may have the potential of becoming pregnant (including those who are pre-menopausal, not amenorrheic due to receiving medication, or not having undergone sterilization surgery), patients who agree to perform appropriate contraception during the study period. In the case of men, patients who agree to perform appropriate contraception during the study period.

Exclude criteria

Patients who meet any of the following conditions will be excluded.
1) Patients suffering from or who have a history of the following conditions:
(i) Moderate to severe aortic or mitral valve disease
(ii) Abnormal thyroid function
(iii) Ischemic heart disease (including myocardial infarction)
(iv) Cardiomyopathy and other myocardial diseases
(v) Malignant diseases within the past five years
2) Patients who have an implantable defibrillator.
3) Patients who received the following drugs within 3 months prior to the baseline examination.
(i) Amiodarone
(ii) Bepridil
4) Patients who underwent catheter ablation within 3 months prior to the baseline examination.
5) Patients with concomitant interstitial lung pneumonia.
6) Patients with an active infection requiring systemic treatment.
7) Patients who have participated in another clinical trial with administration of a study drug within 1 month prior to administration of this study drug, or who plan to simultaneously participate in another clinical trial.
8) Women who are pregnant (including patients with a positive pregnancy test at screening) or are lactating during the study period or who wish to become pregnant. This does not apply if breastfeeding is discontinued (from the date of obtaining consent to 30 days after the end of study drug administration). In women, a beta-HCG test will be performed to check for the presence of pregnancy. Men who do not agree to adequate contraception during the study period.
9) Patients with psychiatric disorders that can cause problems in terms of tracking and compliance with the study protocol.
10) Patients who are considered to be inappropriate for the study according to the discretion of the physicians.

Related Information

• Primary Sponsor: Asano Yoshihiro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development