A Phase 2a Trial to Investigate Safety, Tolerability and Exploratory Efficacy of AGP100 in Patients with Catecholaminergic Polymorphic Ventricular Tachycardia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Agiana Pharmaceuticals AS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Dec 2025 → ongoing

Decision date (initial)

2025-10-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

To assess safety and tolerability of increasing doses of AGP100 in patients with genetically confirmed CPVT and residual ventricular ectopy at exercise testing at stable doses of current standard of care.

Secondary objectives 2

1. To assess the effect of AGP100 treatment on the amount and complexity of exercise induced ectopy.
2. To assess the pharmacodynamics (blood and urine cGMP and cAMP levels) of multiple ascending doses of AGP100 in patients with CPVT.

Conditions and MedDRA coding

Catecholaminergic Polymorphic Ventricular Tachycardia

Regulatory references

Scientific advice from competent authorities

Norwegian Medical Products Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent prior to any study-related procedures
2. Male or female, aged between 18 and 75 years (inclusive)
3. Clinical diagnosis of CPVT based on proven RYR2 mutation AND reproducible premature ventricular contraction with exercise or polymorphic or bidirectional ventricular tachycardia with exercise
4. Able and willing to undergo exercise testing (bicycle test) AND exhibits exercise-induced ventricular ectopic beats at Screening (at least 1 point on the VA scale)
5. On stable, maximum tolerated, dose of non-selective β-blocker for at least 4 weeks before Visit 1. The dosage and choice of β-blocker are to be determined by the patients’ physician(s) before entry into the study and must remain unchanged throughout the conduct of the study. Participants taking a stable dose of flecainide for at least 4 weeks, in addition to β-blocker, are also eligible. If the patient is taking a daily dose of the non-selective β-blocker nadolol, this must be taken in the evening.
6. Clinical laboratory evaluations including clinical chemistry, haematology, urinalysis, thyroid function (including thyroid stimulating hormone [TSH], triiodothyronine [T3], thyroxine [T4], and free T4) and coagulation testing (activated partial thromboplastin time [aPTT], and international normalized ratio [INR]) within the reference range, unless deemed not clinically significant by the Investigator
7. Willing to refrain from strenuous or new exercise for 24 hours before each study visit
8. Women of childbearing potential (WOCBP 1) agree to implement accepted and highly effective means of contraception from study entry until at least 33 days after study drug discontinuation (as per the Clinical Trials Facilitation and Coordination Group [CTFG] guidelines). Highly effective methods of birth control are defined as those that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable); intrauterine devices (IUDs); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; sexual abstinence; vasectomised partner. 1 A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Procedures must have been completed at least 6 months prior to Baseline. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

Exclusion criteria 28

1. Diagnosis of structural heart disease, including coronary artery disease or heart failure with reduced ejection fraction (left ventricular ejection fraction < 45%)
2. Participants who have had arrhythmias causing hemodynamic instability at previous exercise tests (performed while on the current standard of care treatment)
3. Participants having a sustained VT (VA score of 5) during the exercise tests performed as part of the screening activities
4. Participation in another clinical study with an investigational product or device within 60 days of 5 half-lives prior to Baseline (whichever is longer)
5. Medical history of severe anaphylactic reactions to any component(s) of the IMP
6. Sensitivity to any of the study treatments, or components thereof, or any drug or other allergy that, in the opinion of the Investigator, precludes participation in the study
7. Hypersensitivity or contraindication to PDE2 inhibitor drugs
8. Use of PDE3, PDE4, or PDE5 inhibitor drugs. See Appendix B for Prohibited Medication
9. Participants taking any antiarrhythmic drug(s) except flecainide and non-selective β-blockers
10. Significant hypertension (defined as systolic blood pressure of >160 mmHg and/or diastolic blood pressure of >95 mmHg). If the blood pressure results are out of range at Screening, the measurements can be repeated on the same day more than once, or at another convenient visit
11. Prolonged PR and/or QTc interval at Screening, defined as PR >240 ms or QTc >480 ms
12. Positive pregnancy test at Screening or Baseline
13. Female participants who are nursing
14. WOCBP potential who do not fulfil the criteria as defined in inclusion criterion 8
15. Known active infection or major haematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction, as judged by the Investigator at Baseline
16. Severe renal impairment (e.g., estimated glomerular filtration rate <30 mL/min at Screening) or severe hepatic impairment (ASAT, ALAT, ALP or GGT > 2.5 times upper limit of normal (ULN) or bilirubin >1.5 times ULN at Screening)
17. Current or recent (within 3 months of Baseline) gastrointestinal disease
18. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the IMP
19. Regular use of anticoagulants or platelet inhibitors (including aspirin)
20. Use of any medications, or dietary or herbal supplements, prescription or available over the counter, which are known to chronically alter drug absorption or elimination processes, known to induce or inhibit CYP3A4 or CYP2B6 are contraindicated for treatment with PDE2 inhibitors within 30 days or 5 half-lives (whichever is longer) of Baseline. See Appendix B for Prohibited Medication.
21. Ingestion of grapefruit-containing foods or beverages in the 14 days prior to Baseline.
22. Plasma donation in the 28 days prior to Baseline or blood donation or equivalent blood loss in the 3 months prior to Baseline
23. Diagnosis of cancer in the 5 years prior to Baseline, with the exception of basal cell or squamous cell carcinoma of the skin that has been cured or cervical carcinoma in situ that has been cured
24. History of major psychiatric disorders (e.g., major depressive disorder, bipolar disorder, schizophrenia and schizoaffective disorder, personality disorder) within 12 months prior to Screening
25. History of drug abuse or excessive alcohol use within 12 months prior to Screening
26. Participants who, in the opinion of the investigator, are not suitable candidates for the study
27. Participants who are judged unable to comply with the requirements of the study as judged by the Investigator
28. Participants under judicial supervision, guardianship, or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety: Incidence of AEs from receipt of the first dose of IMP and changes in standard safety assessments (which include physical examinations, vital signs, body weight, 12-lead ECG, and safety laboratory assessments)
2. Tolerability (‘Tolerable Yes or No’): If any of following changes in IMP dosing is deemed necessary, the participant will be classified as ‘No’. • Dose adjustments prescribed by the Investigator • Dose interruptions prescribed by the Investigator • Discontinuation of treatment

Secondary endpoints 2

1. Change from Baseline in the amount and complexity of exercise-induced ventricular ectopic beats as assessed using the ventricular arrythmia (VA) score at Day 1, Day 14, Day 27, Day 39, and Day 68.
2. Change from Baseline in urine and plasma cGMP and cAMP levels at Day 1 (post-dose), Day 14, Day 27, Day 39, and Day 68.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Agiana Pharmaceuticals AS

Sponsor organisation

Agiana Pharmaceuticals AS

Address

Gaustadalleen 21

City

Oslo

Postcode

0349

Country

Norway

Scientific contact point

Organisation

Agiana Pharmaceuticals AS

Contact name

Ida Skrinde Leren

Public contact point

Organisation

Agiana Pharmaceuticals AS

Contact name

Rizwan Hussein

Third parties 4

Locations

1 EU/EEA country · 1 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 6 files

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

Application history

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