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

NCT06616974 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TX000045-003
• Study Type: interventional
• Target: 191
• Locations: 16 countries
• Sites: 71

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).

Conditions

Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (5)

• 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

• 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

Secondary Outcomes (10)

• Mean change from baseline in pulmonary capillary wedge pressure (PCWP).

  Baseline to Week 24 post first dose

• Mean change from baseline in PVR for all participants.

  Baseline to Week 24 post first dose

• Mean change from baseline in cardiac output (CO) for all participants and in participants with CpcPH.

  Baseline to Week 24 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

• Mean change from baseline in total pulmonary resistance (TPR) for all participants and in participants with CpcPH.

  Baseline to Week 24 post first dose

Study Arms (3)

TX000045 Dose A

EXPERIMENTAL

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

TX000045 Dose B

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants will receive a single placebo dose SC for 24 weeks from Day 1 to Day 155

Drug: Placebo

Interventions

TX000045- Dose A DRUG

The participants will receive a subcutaneous injection of Dose A of TX000045 every 2 weeks for 24 weeks.

TX000045 Dose A

TX000045- Dose B DRUG

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.

TX000045 Dose B

Placebo DRUG

The participants will receive a subcutaneous injection of placebo every 2 weeks for 24 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 83 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5.
• Current or recent hospitalization prior to screening.
• Recently received vasoactive drugs, pulmonary arterial hypertension-specific therapies, or a relaxin receptor agonist.
• Initiated a new exercise program for cardiopulmonary rehabilitation or plans to initiate such a program during the study.
• Has a body mass index \<18 kg/meter square or \>45 kg/ meter square.
• Was previously administered TX000045, relaxin, or a relaxin fusion protein.
• Historical or current evidence of a clinically significant disease or disorder such as significant lung disease, cardiovascular comorbitiies, liver disease, infectious disease, or malignancy.
• Has any of the following clinical laboratory values during screening:
• Serum alanine aminotransferase or aspartate aminotransferase levels \> 3 x the upper limit of normal (ULN) or total bilirubin \> 3 x ULN;
• eGFR \<30 mL/min/1.73 m2;
• HbA1c (glycosylated hemoglobin) \>9%;
• Platelet count \<50,000/millimeter cube;
• Hemoglobin \<10.0g/dL;
• History of hypersensitivity or reactions to drugs with a similar chemical structure or class to TX000045.
• Is pregnant or breastfeeding.

Sponsors & Collaborators

• Tectonic Therapeutic: lead

Study Sites (72)

Phoenix

Phoenix, Arizona, 85283, United States

Location

Scottsdale

Scottsdale, Arizona, 85258, United States

Location

San Francisco

San Francisco, California, 94143, United States

Location

Santa Rosa

Santa Rosa, California, 95405, United States

Location

Aurora

Aurora, Colorado, 80045, United States

Location

Jacksonville

Jacksonville, Florida, 32216, United States

Location

Augusta

Augusta, Georgia, 30912, United States

Location

McDonough

McDonough, Georgia, 30253, United States

Location

Boise

Boise, Idaho, 83706, United States

Location

USA

Louisville, Kentucky, 40202, United States

Location

Baltimore

Baltimore, Maryland, 21201, United States

Location

Boston

Boston, Massachusetts, 02180, United States

Location

Minneapolis

Minneapolis, Minnesota, 55414, United States

Location

St Louis

St Louis, Missouri, 63110, United States

Location

Omaha

Omaha, Nebraska, 68198, United States

Location

New York

New York, New York, 10029, United States

Location

New York

New York, New York, 10075, United States

Location

Durham

Durham, North Carolina, 27710, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19107, United States

Location

Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

York

York, Pennsylvania, 17403, United States

Location

Port Arthur

Port Arthur, Texas, 77642, United States

Location

Waco

Waco, Texas, 76712, United States

Location

Salt Lake City

Salt Lake City, Utah, 84112, United States

Location

United States

Norfolk, Virginia, 23507, United States

Location

Yerevan

Yerevan, 0006, Armenia

Location

Yerevan

Yerevan, 0025, Armenia

Location

Yerevan

Yerevan, 0087, Armenia

Location

Camperdown

Camperdown, New South Wales, 2050, Australia

Location

Macquarie

Macquarie, New South Wales, 2109, Australia

Location

New Lambton

New Lambton, New South Wales, 2305, Australia

Location

Sydney

Sydney, New South Wales, 2010, Australia

Location

Wollongong

Wollongong, New South Wales, 2500, Australia

Location

Chermside

Chermside, Queensland, 4032, Australia

Location

Hobart

Hobart, Tasmania, 7000, Australia

Location

Malvern

Malvern, Victoria, 3145, Australia

Location

Camperdown

Camperdown, 2050, Australia

Location

New Lambton

New Lambton, 2305, Australia

Location

Austria

Vienna, 1100, Austria

Location

Brussel

Brussels, 1070, Belgium

Location

Pleven

Pleven, 5800, Bulgaria

Location

Plovdiv

Plovdiv, 4001, Bulgaria

Location

Tbilisi

Tbilisi, Tb, 0186, Georgia

Location

Tbilisi

Tbilisi, 0159, Georgia

Location

Tbilisi

Tbilisi, 0167, Georgia

Location

Tbilisi

Tbilisi, 0191, Georgia

Location

Mainz

Mainz, 55131, Germany

Location

Riga

Riga, LV10002, Latvia

Location

Chisinau

Chisinau, Moldova

Location

Christchurch

Christchurch, 8011, New Zealand

Location

Białystok

Bialystok, 15-276, Poland

Location

Krakow

Krakow, 31-202, Poland

Location

Łodź

Lodz, 91-347, Poland

Location

Lublin

Lublin, 20-090, Poland

Location

Warsaw

Warsaw, 04-628, Poland

Location

Wrocław

Wroclaw, 50-556, Poland

Location

Almada

Almada, 2805-267, Portugal

Location

Lisboa

Lisbon, 1649-028, Portugal

Location

Porto

Porto, 4099-001, Portugal

Location

Bucuresti

Bucharest, 022328, Romania

Location

Craiova

Craiova, 200642, Romania

Location

Targu Mures

Târgu Mureş, 540136, Romania

Location

Nis, Belgrade

Belgrade, Nis, 18108, Serbia

Location

Serbia

Belgrade, 11040, Serbia

Location

Sremska Kamenica

Kamenitz, 21204, Serbia

Location

Kragujevac

Kragujevac, 34000, Serbia

Location

Barcelona

Barcelona, 08035, Spain

Location

Madrid

Madrid, 28034, Spain

Location

Madrid

Madrid, 28041, Spain

Location

Santiago de Compostela ( Coruña )

Santiago de Compostela, 15706, Spain

Location

Valencia

Valencia, 46010, Spain

Location

Ukraine

Kyiv, 01135, Ukraine

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Robert Rogers, MD

  Tectonic Therapeutic

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: September 27, 2024
• Study Start: September 4, 2024
• Primary Completion (Estimated): November 24, 2026
• Study Completion (Estimated): January 5, 2027
• Last Updated: July 7, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

LA (1); BU (2); PT (3); ES (5); GE (4); UA (1); AU (10); RO (3); BE (1); DE (1); US (25); AR (3); SE (4); NZ (1); PL (6); MO (1)