A 24-Week Study of TX000045 in Patients With Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction (PH-HFpEF) (the APEX Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tectonic Therapeutic 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 Dec 2024 → ongoing

Decision date (initial)

2025-12-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the effect of TX000045 vs placebo on mean PVR in participants with baseline PVR ≥3 Wood units.
To evaluate the safety of TX000045 in participants with PH-HFpEF

Secondary objectives 1

1. To evaluate the effect of TX000045 on pulmonary capillary wedge pressure (PCWP) in all participants with PH-HFpEF

Conditions and MedDRA coding

Pulmonary Hypertension

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Is a male or female of non–childbearing potential between the ages of 18 and 83 years.
2. 2. Has a diagnosis of PH-HFpEF based on ALL the following criteria: a) The baseline echocardiogram, performed during screening, demonstrates the following: left ventricular ejection fraction (LVEF) >40%, tricuspid regurgitation gradient peak >36 mm Hg, and SPAP >41 mm Hg.
3. 3. Has NYHA functional class II-III heart failure
4. 4. Has 6MWT distance ≥100 m and ≤450 m, repeated during screening.
5. 5. If the participant is receiving chronic medication for the treatment of heart failure, including diuretics, or any other cardiovascular condition (including systemic hypertension), the dose must be stable for ≥30 days before start of screening.

Exclusion criteria 22

1. 1. Has a confirmed diagnosis of PH in WHO Group 1 (pulmonary arterial hypertension), WHO Group 3 (PH associated with significant lung disease), WHO Group 4 (PH associated with chronic thromboembolic disease), or WHO Group 5
2. Has documented significant lung disease
3. 11. Has cardiovascular comorbidities
4. Has chronic liver disease (other than congestive hepatopathy), active hepatitis B infection (positive hepatitis B surface antigen and positive hepatitis B core antibodies), or hepatitis C infection (positive hepatitis C antibodies) at the screening visit. In patients with isolated positive hepatitis B core antibodies, a hepatitis B DNA test will be performed. If positive, the participant will be excluded from the study due to active hepatitis B.
5. 14. Has HIV infection or HIV seropositivity at the screening visit
6. 15. Has an active tuberculosis infection
7. 16. Has any of the following clinical laboratory values during screening: a) Serum alanine aminotransferase or aspartate aminotransferase levels >3× the upper limit of normal (ULN) or total bilirubin >3× ULN b) Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 (CKD EPI [Chronic Kidney Disease Epidemiology Collaboration] equation) or required renal replacement therapy (eg, ultrafiltration or dialysis) within 90 days before the start of screening c) HbA1c (glycosylated hemoglobin) >9% d) Platelet count <50,000/mm3 e) Hemoglobin <10.0g/dL
8. 17. Has a history of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
9. 18. Had major surgery within 60 days before the start of screening.
10. 2. Was hospitalized for any indication within 7 days before the start of screening
11. 20. Is pregnant or breastfeeding
12. 22. Has a history of active malignancy within 5 years before the start of screening, except for fully excised or treated basal cell carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin
13. 23. Has a history of drug or alcohol abuse
14. 24. Was dosed in any clinical research study evaluating another investigational drug (including biologics) or therapy
15. 25. Has significant orthopedic or arthritic disease that limits the ability to complete a 6MWT
16. 26. Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of significant psychiatric disorders at the discretion of the investigator
17. 27. Has a history of any illness that, in the opinion of the investigator, poses additional risk to the participant
18. 3. Received IV vasoactive therapies inotropes
19. 5. Initiated a new exercise program within 90 days before the start of screening or plans to initiate such a program during the study (patients who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
20. 6. Has a body mass index (BMI) <18 kg/m2 or >50 kg/m2
21. 7. Was previously administered TX000045, relaxin, or a relaxin fusion protein
22. 8. Received a small molecule RXFP1 agonist within 30 days before the start of screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Mean change from baseline to Week 24 in PVR as measured by right heart catheterization (RHC) in participants with baseline PVR ≥3 Wood units who received TX000045 compared with those who received placebo
2. In participants who received TX000045 compared with placebo, describe: • Incidence of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) • Incidence of clinically significant changes from baseline in laboratory assessments, 12-lead electrocardiogram (ECG), vital sign assessments, and physical examinations

Secondary endpoints 1

1. Mean change from baseline to Week 24 in PVR as measured by right heart catheterization (RHC) in participants with baseline PVR ≥3 Wood units who received TX000045 compared with those who received placebo

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tectonic Therapeutic Inc.

Sponsor organisation

Tectonic Therapeutic Inc.

Address

490 Arsenal Way

City

Watertown

Postcode

02472-2988

Country

United States

Scientific contact point

Organisation

Tectonic Therapeutic Inc.

Contact name

Anthony Muslin

Public contact point

Organisation

Tectonic Therapeutic Inc.

Contact name

Mary Carioto-Moreta

Third parties 11

Locations

9 EU/EEA countries · 31 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 173 files

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

Application history

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