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

Phase 2

Recruiting

• Conditions: Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction
• Interventions: Drug: Placebo; Drug: TX000045- Dose A; Drug: TX000045- Dose B

• Registration Number: NCT06616974
• Lead Sponsor: Tectonic Therapeutic

Brief Summary

TX000045-003 is a double-blind, randomized, parallel group, placebo-controlled, proof- of-concept (POC) study, evaluating 2 dose regimens of TX000045 over the course of a 24-week treatment period (the APEX study).

Detailed Description

This study will enroll approximately 180 participants and eligible patients will be randomized to one of 3 treatment arms:

* Arm 1: Treatment Group 1: Placebo delivered subcutaneously (SC) every 2 weeks (Q2W) for 24 weeks

* Arm 2: Treatment Group 2: TX000045 SC at Dose A Q2W for 24 weeks

* Arm 3: Treatment Group 3: TX000045 SC at Dose B Q2W alternating with Placebo Q2W for 24 weeks

Study Timeline

• Study First Submitted: 2024-09-19
• Study First Submitted QC: 2024-09-25
• Study First Posted: 2024-09-27
• Study Start: 2024-10-08
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-15
• Primary Completion: 2026-10-09
• Study Completion: 2026-11-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Is a male or female of non-childbearing potential between the ages of 18 and 83 years.
2. Has a diagnosis of PH-HFpEF based on baseline echocardiogram and right heart catheterization (RHC).
3. Has NYHA functional class II- III heart failure.
4. Has 6MWT distance from 100 to 450m.
5. Chronic medication for heart failure or cardiovascular disease is at a stable dose prior to screening.
6. Is able to understand and provide documented consent for participation.

Exclusion Criteria

1. Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5.

2. Current or recent hospitalization prior to screening.

3. Recently received vasoactive drugs, pulmonary arterial hypertension-specific therapies, or a relaxin receptor agonist.

4. Initiated a new exercise program for cardiopulmonary rehabilitation or plans to initiate such a program during the study.

5. Has a body mass index <18 kg/meter square or >45 kg/ meter square.

6. Was previously administered TX000045, relaxin, or a relaxin fusion protein.

7. Historical or current evidence of a clinically significant disease or disorder such as significant lung disease, cardiovascular comorbitiies, liver disease, infectious disease, or malignancy.

8. Has any of the following clinical laboratory values during screening:

   1. Serum alanine aminotransferase or aspartate aminotransferase levels > 3 x the upper limit of normal (ULN) or total bilirubin > 3 x ULN;
   2. eGFR <30 mL/min/1.73 m2;
   3. HbA1c (glycosylated hemoglobin) >9%;
   4. Platelet count <50,000/millimeter cube;
   5. Hemoglobin <10.0g/dL;

9. History of hypersensitivity or reactions to drugs with a similar chemical structure or class to TX000045.

10. Is pregnant or breastfeeding.

11. Has a history of cancer within 5 years of screening other than basal cell carcinoma, cervical carcinoma, or squamous cell carcinomas of the skin.

12. Has a history of drug or alcohol abuse.

13. Was recently dosed in any clinical research study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive a single placebo dose SC for 24 weeks from Day 1 to Day 155
TX000045 Dose A	TX000045- Dose A	Participants will receive a single dose of TX000045 Dose A subcutaneously every 2 weeks for 24 weeks from Day 1 to Day 155.
TX000045 Dose B	TX000045- Dose B	Participants will receive alternating single doses of TX000045 Dose B and placebo subcutaneously every 2 weeks for 24 weeks from Day 1 to Day 155.

Primary Outcome Measures

Name	Time	Method
Assess safety of TX000045 by the incidence of adverse events, adverse events of special interest and SAEs.	Baseline up to Week 30 post first dose
Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.	Baseline up to Week 30 post first dose
Number of participants with treatment-related adverse events.	Baseline up to Week 30 post first dose
Number of participants with changes in the physical examination findings.	Baseline to Week 30 post first dose
Mean change from baseline in Pulmonary Vascular Resistance (PVR) in participants with a combined pre- and post-capillary pulmonary hypertension (CpcPH).	Baseline up to Week 24 post first dose	Measured by right heart catheterization (RHC) between those who received TX000045 and those with placebo.

Secondary Outcome Measures

Name	Time	Method
Mean change from baseline in pulmonary capillary wedge pressure (PCWP).	Baseline to Week 24 post first dose	Measured by RHC between those who received TX000045 and those with placebo.
Mean change from baseline in PVR for all participants.	Baseline to Week 24 post first dose	Measured by RHC between those who received TX000045 and those with placebo.
Mean change from baseline in cardiac output (CO) for all participants and in participants with CpcPH.	Baseline to Week 24 post first dose	This is measured by RHC between those who received TX000045 and those with placebo.
Mean change from baseline in total pulmonary resistance (TPR) for all participants and in participants with CpcPH.	Baseline to Week 24 post first dose	This is measured by RHC between those who received TX000045 and those with placebo.
Mean change from baseline in mean pulmonary arterial pressure (mPAP) for all participants and in participants with CpcPH.	Baseline to Week 24 post first dose	This is measured by RHC between those who received TX000045 and those with placebo.
Mean change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) for all participants and in participants with CpcPH between those who received TX000045 and those with placebo.	Baseline to Week 30 post first dose
Number of participants with change in antibody titers following treatment with TX000045 (Immunogenicity).	Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose
Mean change from baseline in exercise capacity in all participants and in participants with CpcPH.	Baseline to Week 30 post first dose	This is measured by mean change from baseline in 6-minute walk test (6MWT) distance between those who received TX000045 and those with placebo.
Mean change from baseline responses on the Kansas City Cardiomyopathy Questionnaire (KCCQ) for all participants and in participants with CpcPH.	Baseline to Week 24 post first dose	To evaluate the effect of TX000045 vs. Placebo on KCCQ scores. KCCQ-12 is a validated tool to assess quality of life in patients with heart failure. It contains 4 subdomains: physical limitation, symptom frequency, QOL, and social limitations. Each subdomain provides an individual score from 0 to 100, with 0 denoting the worst and 100 the best possible health status.
Evaluate the serum concentrations of TX000045.	Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose

Trial Locations

Locations (56)

Santiago de Compostela ( Coruña ); 🇪🇸 Santiago De Compostela, Spain

Valencia; 🇪🇸 Valencia, Spain

Madrid; 🇪🇸 Madrid, Spain

Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

San Francisco; 🇺🇸 San Francisco, California, United States

Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Tampa; 🇺🇸 Tampa, Florida, United States

Augusta; 🇺🇸 Augusta, Georgia, United States

McDonough; 🇺🇸 McDonough, Georgia, United States

Chicago; 🇺🇸 Chicago, Illinois, United States

Baltimore; 🇺🇸 Baltimore, Maryland, United States

Omaha; 🇺🇸 Omaha, Nebraska, United States

Rock Hill; 🇺🇸 Rock Hill, South Carolina, United States

Waco; 🇺🇸 Waco, Texas, United States

Salt Lake City; 🇺🇸 Salt Lake City, Utah, United States

Macquarie; 🇦🇺 Macquarie, New South Wales, Australia

Sydney; 🇦🇺 Sydney, New South Wales, Australia

Malvern; 🇦🇺 Malvern, Victoria, Australia

Brussel; 🇧🇪 Brussel, Belgium

Genk; 🇧🇪 Genk, Belgium

Riga; 🇱🇻 Riga, Latvia

Dunedin; 🇳🇿 Dunedin, New Zealand

Warsaw; 🇵🇱 Warsaw, Poland

Craiova; 🇷🇴 Craiova, Romania

Targu Mures; 🇷🇴 Târgu-Mureş, Romania

Birmingham; 🇺🇸 Birmingham, Alabama, United States

Aurora; 🇺🇸 Aurora, Colorado, United States

Covington; 🇺🇸 Covington, Louisiana, United States

St Louis; 🇺🇸 Saint Louis, Missouri, United States

Toledo; 🇺🇸 Toledo, Ohio, United States

Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Boston; 🇺🇸 Boston, Massachusetts, United States

Jackson; 🇺🇸 Jackson, Mississippi, United States

New York; 🇺🇸 New York, New York, United States

Durham; 🇺🇸 Durham, North Carolina, United States

Hobart; 🇦🇺 Hobart, Tasmania, Australia

Pleven; 🇧🇬 Pleven, Bulgaria

Plovdiv; 🇧🇬 Plovdiv, Bulgaria

Sofia; 🇧🇬 Sofia, Bulgaria

Tbilisi; 🇬🇪 Tbilisi, Georgia

Hamburg; 🇩🇪 Hamburg, Germany

York; 🇺🇸 York, Pennsylvania, United States

Beaumont; 🇺🇸 Beaumont, Texas, United States

Yerevan; 🇦🇲 Yerevan, Armenia

Wollongong; 🇦🇺 Wollongong, New South Wales, Australia

Auchenflower; 🇦🇺 Auchenflower, Queensland, Australia

Chermside; 🇦🇺 Chermside, Queensland, Australia

Port Arthur; 🇺🇸 Port Arthur, Texas, United States

Mainz; 🇩🇪 Mainz, Germany

Chisinau; 🇲🇩 Chisinau, Moldova, Republic of

Christchurch; 🇳🇿 Christchurch, New Zealand

Białystok; 🇵🇱 Białystok, Poland

Krakow; 🇵🇱 Kraków, Poland

Lublin; 🇵🇱 Lublin, Poland

Łodź; 🇵🇱 Łódź, Poland

Barcelona; 🇪🇸 Barcelona, Spain