Outcome Research to Confirm the Anti-anginal Effect of T89 in Patients with Stable Angina (ORESA Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tasly Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

19 May 2025 → ongoing

Decision date (initial)

2024-11-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512313-41-00

ClinicalTrials.gov

NCT03789552

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To confirm the anti-anginal effect of T89 in patients with chronic stable angina pectoris.

Secondary objectives 1

1. To evaluate the long-term safety of T89 in patients with chronic stable angina pectoris.

Conditions and MedDRA coding

Stable Angina Pectoris

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Willing to participate and sign a written informed consent
2. Males and females ≥ 18 and ≤90 years old
3. Medical history of chronic stable angina triggered by physical effort and relieved by rest or sublingual nitroglycerin. Patients with grade II and III stable angina based on Canadian Cardiovascular Society angina grading.
4. Patients who agree and in the opinion of the investigator are able to withdraw all non-beta blocker and all non-calcium channel blocker anti-anginal medications. For those subjects who are on one beta blocker or one calcium channel blocker can keep their medication. And patients agree and are expected to be able to remain on this treatment regimen from Day -21 until the completion of the double-blind period in the opinion of the investigator. For patients who have to modify their anti-anginal treatment regimen to meet the above qualification criteria, health care provider who is responsible for the patient's cardiac care (if this is not the study doctor) must provide a form of agreement (verbal conversation, phone call, in writing or shown as referral) to the PI before the treatment modification. For patients who are not on beta blocker or calcium channel blocker or other antianginal medications, there is no requirement to start on antianginal medication.
5. Documented history of coronary artery disease with one or more of the following conditions: History of previous myocardial infarction (previous MI that occurred and was diagnosed at least 3 months prior to start of screening). Ischemic heart disease determined by stress myocardial imaging examination (including nuclear stress test, cardiac stress MRI and echocardiography stress test). Clinically significant coronary stenosis ≥50% in any vessel detected by coronary angiography (or coronary CT angiography).
6. Understand and be willing, able and likely to comply with all study procedures and restrictions and comprehends the Seattle Angina Questionnaire rating scales and diary cards.
7. Women of child bearing potential: Female patients of child-bearing potential or male patients with partners of child-bearing potential must use highly effective birth control methods from the start of screening, until 3 months after the last dose of study medication (for details please refer to Appendix III). Female patients of child bearing potential must have negative pregnancy tests at screening visit [Day -21, quantitative serum human chorionic gonadotropin (β-hCG test)] and randomization visit (Day 1, urine pregnancy test).
8. Patient must experience two or more angina episodes from Day-14 to Day 1, as the baseline frequency of angina. At least two of the angina episodes must be recorded by WCM (Other written forms of recording/reporting angina episodes may be acceptable only in situations and times that recording by WCM is impractical). In addition, patients are allowed to use short acting nitroglycerin for relief of angina.
9. To be qualified, patients must have two qualifying ETTs on standard Bruce protocol on Day- 7 and Day 1. The qualifying ETTs are: ETTs must meet the positive ETT criteria (refer to ETT explanation section 1.6 and 3.2.4); Total exercise duration (TED) of the positive ETT is between 3-12 minutes of exercise; The difference in TED between the two ETTs must not exceed 15% of the longer one.
10. Patients on antiplatelet drugs (except aspirin or clopidogrel), statins, ACE inhibitor, angiotensin II receptor blocker (ARB), warfarin or other direct acting oral anticoagulants (DOACs) need to be stable at current dose for at least 2 weeks prior to the start of screening.

Exclusion criteria 20

1. Patients with only non-cardiac chest pain or cardiac chest pain not related to angina.
2. Patient with uncontrolled hypertension characterized by seated systolic blood pressure >180mm Hg or diastolic blood pressure >100mm Hg, within 2 months prior to, or during, the Single Blind Qualifying Period. Or patients with severe congenital cardiac defects, severe valvular disease, suspected or known dissecting aortic aneurysm and hypertrophic cardiomyopathy should be excluded.
3. Patients with hemoglobin (HGB) <10 g/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2×upper limit of normal (ULN), hemoglobin A1C (HbA1C) >10%, or glomerular filtration rate (GFR) <30cc/min, in any of the single blind qualifying lab tests.
4. Patient with history of bleeding diathesis or cerebral hemorrhage or seizure disorder that need anticonvulsant.
5. Patients who have to be on ranolazine, ivabradine and patients who have to be on both beta blocker and calcium channel blocker, more than one beta blockers or calcium channel blockers, or other anti-anginal agent other than only sublingual nitroglycerin for on-demand angina relief.
6. Patients who have to be on digoxin, digitalis, or other herbal products containing Danshen (Radix Salviae Miltiorrhizae, RSM), Sanqi (Radix Notoginseng, RN) or Ginkgo biloba during the single-blind screening and/or double-blind treatment period.
7. Clinical trials/experimental medication: participation in any other clinical trial or receipt of an investigational drug or device within 30 days prior to the start of screening.
8. Female patients with known, suspected or planned pregnancy, or lactation.
9. Patients with a recent (within the last 2 years) history of substance abuse (alcohol, marijuana, or known drug dependence). Or patients who have a positive urine substance screening test at the Day -21 initial visit.
10. Any family member or relative of the study site staff, sponsor or CRO.
11. Patients with contraindication to, unable to, or with other co-morbidities that may prevent or interfere with the ability to perform ETT, in the opinion of investigator, including but not limited to: hospitalization for acute exacerbation of chronic lung disease within 4 weeks prior to the start of screening, current home oxygen use, needs for cardiac glycoside therapy, functionally limiting peripheral arterial disease, physical disability or other intercurrent illness such as acute respiratory infection/illness that, in the opinion of the Investigator or Sub-investigator, may interfere with the ability to perform ETT.
12. Patients with any other severe or serious condition that, in the opinion of the investigator is likely to prevent compliance with the study protocol or pose a safety concern if the patient participates in the study.
13. Patients whose QTcF (Fridericia’s method corrected QT interval) is >460 ms in male and >470 ms in female during supine 12-lead ECG at rest at screening or any time prior to randomization from Day -21.
14. Patients with presence of electrographic or other abnormalities/factors that could interfere with exercise ECG interpretation or may lead to a false positive stress test (including but not limited to, Lown-Ganong-Levine Syndrome (LGL), Wolff-Parkinson-White Syndrome (WPW), left bundle branch block, ≥1 mm ST segment depression at rest, pacemaker rhythm etc.).
15. Patients with history of any coronary revascularization procedure (e.g. PCI or CABG) within 2 months prior to the start of screening.
16. Patients who had unstable angina, or myocardial infarction within the recent 3 months prior to the start of screening.
17. Patients with ongoing NYHA Classes III-IV congestive heart failure.
18. Patients with angina pectoris at rest at screening.
19. Patients with rapid atrial fibrillation at screening (rest heart rate >120/min) or any time prior to randomization from Day -21.
20. Patients with ongoing myocarditis, pericarditis, thrombophlebitis or pulmonary embolism or who have recovered from these conditions <1 month prior to screening. Note: Patients who are on anticoagulant prophylaxis just for a pulmonary embolism or thrombophlebitis will not be subject to the one-month restriction.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Efficacy endpoint: Change in symptom-limited total exercise duration (TED) at trough drug levels on standard Bruce protocol from baseline to Day 57.
2. Safety endpoints: Frequency and severity of adverse events and serious adverse events
3. Safety endpoints: Notable laboratory abnormalities which are treatment-emergent

Secondary endpoints 7

1. Efficacy endpoints: The trend of TED changes over time (Slope) from Day 1 to Day 57.
2. Percent change in the average frequency of angina episodes (average over 14 days) from baseline [Day -14 to 1] to the end of double-blind treatment period [Day 43 to 57].
3. Percent change in the average on-demand consumption of short-acting nitroglycerin (average over 14 days) from baseline [Day -14 to 1] to end of double-blind treatment period [Day 43 to 57].
4. Change in symptom-limited total exercise duration (TED) at trough drug levels on standard Bruce protocol from baseline to Day 43;
5. Percent change in the average frequency of angina episodes (average over 14 days) from baseline [Day -14 to 1] to the end of double-blind treatment period [Day 29 to 43].
6. Change in time to the onset of angina during ETT from baseline to Day 57
7. Change in time to the onset of 1 mm ST depression during ETT from baseline to Day 57

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tasly Pharmaceuticals Inc.

Sponsor organisation

Tasly Pharmaceuticals Inc.

Address

9400 Key West Avenue

City

Rockville

Postcode

20850-3322

Country

United States

Scientific contact point

Organisation

Tasly Pharmaceuticals Inc.

Contact name

Xuefeng Su

Public contact point

Organisation

Tasly Pharmaceuticals Inc.

Contact name

Henry Sun

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

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

Documents 59 files

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

Application history

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