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

A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of TX000045 After 24 Weeks of Treatment in Patients With Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction (PH-HFpEF)

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).

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: TX000045- Dose A; Drug: TX000045- Dose B; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials; Phone Number: +1 339 337 4053; Email: ClinicalTrials@tectonictx.com

Study Locations

• Armenia
  • Yerevan, Armenia, 0006
    • Recruiting
    • Yerevan
  • Yerevan, Armenia, 0025
    • Recruiting
    • Yerevan
  • Yerevan, Armenia, 0087
    • Recruiting
    • Yerevan
• Australia
  • Camperdown, Australia, 2050
    • Recruiting
    • Camperdown
  • New Lambton, Australia, 2305
    • Recruiting
    • New Lambton
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Camperdown
    • Macquarie, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie
    • New Lambton, New South Wales, Australia, 2305
      • Recruiting
      • New Lambton
    • Sydney, New South Wales, Australia, 2010
      • Recruiting
      • Sydney
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Wollongong
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Recruiting
      • Auchenflower
    • Chermside, Queensland, Australia, 4032
      • Recruiting
      • Chermside
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Recruiting
      • Hobart
  • Victoria
    • Malvern, Victoria, Australia, 3145
      • Recruiting
      • Malvern
• Austria
  • Vienna, Austria, 1100
    • Recruiting
    • Austria
• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • Brussel
  • Genk, Belgium, 3600
    • Completed
    • Genk
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Recruiting
    • Pleven
  • Plovdiv, Bulgaria, 4001
    • Recruiting
    • Plovdiv
  • Sofia, Bulgaria, 1700
    • Recruiting
    • Sofia
  • Sofia, Bulgaria, 1750
    • Recruiting
    • Sofia
• Georgia
  • Tbilisi, Georgia, 0167
    • Recruiting
    • Tbilisi
  • Tbilisi, Georgia, 0159
    • Recruiting
    • Tbilisi
  • Tbilisi, Georgia, 0191
    • Recruiting
    • Tbilisi
  • Tb
    • Tbilisi, Tb, Georgia, 0186
      • Recruiting
      • Tbilisi
• Germany
  • Mainz, Germany, 55131
    • Recruiting
    • Mainz
• Latvia
  • Riga, Latvia, LV10002
    • Recruiting
    • Riga
• Moldova
  • Chisinau, Moldova
    • Recruiting
    • Chisinau
• New Zealand
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Christchurch
  • Dunedin, New Zealand, 9016
    • Recruiting
    • Dunedin
• Poland
  • Bialystok, Poland, 15-276
    • Recruiting
    • Białystok
  • Krakow, Poland, 31-202
    • Recruiting
    • Krakow
  • Lodz, Poland, 91-347
    • Recruiting
    • Łodź
  • Lublin, Poland, 20-090
    • Recruiting
    • Lublin
  • Warsaw, Poland, 04-628
    • Recruiting
    • Warsaw
  • Wroclaw, Poland, 50-556
    • Recruiting
    • Wrocław
• Portugal
  • Almada, Portugal, 2805-267
    • Recruiting
    • Almada
  • Lisbon, Portugal, 1649-028
    • Recruiting
    • Lisboa
  • Porto, Portugal, 4099-001
    • Recruiting
    • Porto
• Romania
  • Bucharest, Romania, 022328
    • Recruiting
    • Bucuresti
  • Craiova, Romania, 200642
    • Recruiting
    • Craiova
  • Târgu Mureş, Romania, 540136
    • Recruiting
    • Targu Mures
• Serbia
  • Belgrade, Serbia, 11000
    • Recruiting
    • Belgrade
  • Belgrade, Serbia, 11040
    • Recruiting
    • Serbia
  • Kamenitz, Serbia, 21204
    • Recruiting
    • Sremska Kamenica
  • Kragujevac, Serbia, 34000
    • Recruiting
    • Kragujevac
  • Nis
    • Belgrade, Nis, Serbia, 18108
      • Recruiting
      • Nis, Belgrade
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Barcelona
  • Madrid, Spain, 28034
    • Recruiting
    • Madrid
  • Madrid, Spain, 28041
    • Recruiting
    • Madrid
  • Santiago de Compostela, Spain, 15706
    • Recruiting
    • Santiago de Compostela ( Coruña )
  • Toledo, Spain, 45007
    • Recruiting
    • Toledo
  • Valencia, Spain, 46010
    • Recruiting
    • Valencia
  • Valencia, Spain, 46015
    • Recruiting
    • Valencia
• Ukraine
  • Kyiv, Ukraine, 01135
    • Recruiting
    • Ukraine
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85283
      • Recruiting
      • Phoenix
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Scottsdale
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • San Francisco
    • Santa Rosa, California, United States, 95405
      • Recruiting
      • Santa Rosa
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Aurora
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Recruiting
      • Jacksonville
    • Tampa, Florida, United States, 33613
      • Recruiting
      • Tampa
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta
    • McDonough, Georgia, United States, 30253
      • Recruiting
      • McDonough
  • Idaho
    • Boise, Idaho, United States, 83706
      • Recruiting
      • Boise
  • Illinois
    • Chicago, Illinois, United States, 60453
      • Recruiting
      • Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Recruiting
      • Indianapolis
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • USA
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02180
      • Recruiting
      • Boston
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • Minneapolis
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • St Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • Omaha
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • New York
    • New York, New York, United States, 10075
      • Recruiting
      • New York
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Durham
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Recruiting
      • Toledo
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Pittsburgh
    • York, Pennsylvania, United States, 17403
      • Recruiting
      • York
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Recruiting
      • Rock Hill
  • Texas
    • Port Arthur, Texas, United States, 77642
      • Recruiting
      • Port Arthur
    • Waco, Texas, United States, 76712
      • Recruiting
      • Waco
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Salt Lake City
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • United States
    • Richmond, Virginia, United States, 23230
      • Recruiting
      • Richmond

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: TX000045- Dose A; The participants will receive a subcutaneous injection of Dose A of TX000045 every 2 weeks for 24 weeks.
Experimental: 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.	Drug: TX000045- Dose B; The participants will receive subcutaneous injection of Dose B of TX000045 every 4 weeks for 24 weeks where they will alternate between TX000045 and placebo every 2 weeks.
Placebo Comparator: Placebo; Participants will receive a single placebo dose SC for 24 weeks from Day 1 to Day 155	Drug: Placebo; The participants will receive a subcutaneous injection of placebo every 2 weeks for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Mean change from baseline in Pulmonary Vascular Resistance (PVR) in participants with a combined pre- and post-capillary pulmonary hypertension (CpcPH).	Measured by right heart catheterization (RHC) between those who received TX000045 and those with placebo.	Baseline up to Week 24 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in pulmonary capillary wedge pressure (PCWP).	Measured by RHC between those who received TX000045 and those with placebo.	Baseline to Week 24 post first dose
Mean change from baseline in PVR for all participants.	Measured by RHC between those who received TX000045 and those with placebo.	Baseline to Week 24 post first dose
Mean change from baseline in cardiac output (CO) for all participants and in participants with CpcPH.	This is measured by RHC between those who received TX000045 and those with placebo.	Baseline to Week 24 post first dose
Mean change from baseline in exercise capacity in all participants and in participants with CpcPH.	This is measured by mean change from baseline in 6-minute walk test (6MWT) distance between those who received TX000045 and those with placebo.	Baseline to Week 30 post first dose
Mean change from baseline in total pulmonary resistance (TPR) for all participants and in participants with CpcPH.	This is measured by RHC between those who received TX000045 and those with placebo.	Baseline to Week 24 post first dose
Mean change from baseline in mean pulmonary arterial pressure (mPAP) for all participants and in participants with CpcPH.	This is measured by RHC between those who received TX000045 and those with placebo.	Baseline to Week 24 post first dose
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 responses on the Kansas City Cardiomyopathy Questionnaire (KCCQ) for all participants and in participants with CpcPH.	To evaluate the effect of TX000045 vs. Placebo on Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Kansas City Cardiomyopathy Questionnaire (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.	Baseline to Week 24 post first dose
Evaluate the incidence of immunogenicity of TX000045 by the number of participants with detectable anti-drug antibody titers.		Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose

Collaborators and Investigators

• Sponsor: Tectonic Therapeutic
• Investigators: Study Director: Robert Rogers, MD, Tectonic Therapeutic

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2024
• Primary Completion (Estimated): October 9, 2026
• Study Completion (Estimated): November 20, 2026

Study Registration Dates

• First Submitted: September 19, 2024
• First Submitted That Met QC Criteria: September 25, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: TX000045-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No