Clinical trial NCT06616974: A Study of TX000045 in Patients With Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction (the APEX Study)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Hypertension
Heart Failure With Preserved Ejection Fraction
Lead sponsor: Tectonic Therapeutic
Sponsor class: INDUSTRY
First posted: 2024-09-27
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 83
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Mean change from baseline in Pulmonary Vascular Resistance (PVR) in participants with a combined pre- and post-capillary pulmonary hypertension (CpcPH).
timeFrame: Baseline up to Week 24 post first dose
measure: Assess safety of TX000045 by the incidence of adverse events, adverse events of special interest and SAEs.
timeFrame: Baseline up to Week 30 post first dose
measure: Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.
timeFrame: Baseline up to Week 30 post first dose
measure: Number of participants with treatment-related adverse events.
timeFrame: Baseline up to Week 30 post first dose
measure: Number of participants with changes in the physical examination findings.
timeFrame: Baseline to Week 30 post first dose
Secondary outcomes:
measure: Mean change from baseline in pulmonary capillary wedge pressure (PCWP).
timeFrame: Baseline to Week 24 post first dose
measure: Mean change from baseline in PVR for all participants.
timeFrame: Baseline to Week 24 post first dose
measure: Mean change from baseline in cardiac output (CO) for all participants and in participants with CpcPH.
timeFrame: Baseline to Week 24 post first dose
measure: Mean change from baseline in exercise capacity in all participants and in participants with CpcPH.
timeFrame: Baseline to Week 30 post first dose
measure: Mean change from baseline in total pulmonary resistance (TPR) for all participants and in participants with CpcPH.
timeFrame: Baseline to Week 24 post first dose
measure: Mean change from baseline in mean pulmonary arterial pressure (mPAP) for all participants and in participants with CpcPH.
timeFrame: Baseline to Week 24 post first dose
measure: 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.
timeFrame: Baseline to Week 30 post first dose
measure: Mean change from baseline responses on the Kansas City Cardiomyopathy Questionnaire (KCCQ) for all participants and in participants with CpcPH.
timeFrame: Baseline to Week 24 post first dose
measure: Evaluate the serum concentrations of TX000045.
timeFrame: Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose
measure: Number of participants with change in antibody titers following treatment with TX000045 (Immunogenicity).
timeFrame: Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale
state: Arizona
city: San Francisco
country: United States
facility: San Francisco
state: California
city: Aurora
country: United States
facility: Aurora
state: Colorado
city: Jacksonville
country: United States
facility: Jacksonville
state: Florida
city: Tampa
country: United States
facility: Tampa
state: Florida
city: Augusta
country: United States
facility: Augusta
state: Georgia
city: McDonough
country: United States
facility: McDonough
state: Georgia
city: Chicago
country: United States
facility: Chicago
state: Illinois
city: Covington
country: United States
facility: Covington
state: Louisiana
city: Baltimore
country: United States
facility: Baltimore
state: Maryland
city: Boston
country: United States
facility: Boston
state: Massachusetts
city: Jackson
country: United States
facility: Jackson
state: Mississippi
city: Saint Louis
country: United States
facility: St Louis
state: Missouri
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: New York
country: United States
facility: New York
state: New York
city: New York
country: United States
facility: New York
state: New York
city: Durham
country: United States
facility: Durham
state: North Carolina
city: Toledo
country: United States
facility: Toledo
state: Ohio
city: Pittsburgh
country: United States
facility: Pittsburgh
state: Pennsylvania
city: York
country: United States
facility: York
state: Pennsylvania
city: Rock Hill
country: United States
facility: Rock Hill
state: South Carolina
city: Beaumont
country: United States
facility: Beaumont
state: Texas
city: Port Arthur
country: United States
facility: Port Arthur
state: Texas
city: Waco
country: United States
facility: Waco
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
city: Yerevan
country: Armenia
facility: Yerevan
city: Yerevan
country: Armenia
facility: Yerevan
city: Yerevan
country: Armenia
facility: Yerevan
city: Macquarie
country: Australia
facility: Macquarie
state: New South Wales
city: Sydney
country: Australia
facility: Sydney
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong
state: New South Wales
city: Auchenflower
country: Australia
facility: Auchenflower
state: Queensland
city: Chermside
country: Australia
facility: Chermside
state: Queensland
city: Hobart
country: Australia
facility: Hobart
state: Tasmania
city: Malvern
country: Australia
facility: Malvern
state: Victoria
city: Brussel
country: Belgium
facility: Brussel
city: Genk
country: Belgium
facility: Genk
city: Pleven
country: Bulgaria
facility: Pleven
city: Plovdiv
country: Bulgaria
facility: Plovdiv
city: Sofia
country: Bulgaria
facility: Sofia
city: Sofia
country: Bulgaria
facility: Sofia
city: Tbilisi
country: Georgia
facility: Tbilisi
state: Tb
city: Tbilisi
country: Georgia
facility: Tbilisi
city: Hamburg
country: Germany
facility: Hamburg
city: Mainz
country: Germany
facility: Mainz
city: Riga
country: Latvia
facility: Riga
city: Chisinau
country: Moldova, Republic of
facility: Chisinau
city: Christchurch
country: New Zealand
facility: Christchurch
city: Dunedin
country: New Zealand
facility: Dunedin
city: Białystok
country: Poland
facility: Białystok
city: Kraków
country: Poland
facility: Krakow
city: Lublin
country: Poland
facility: Lublin
city: Warsaw
country: Poland
facility: Warsaw
city: Łódź
country: Poland
facility: Łodź
city: Craiova
country: Romania
facility: Craiova
city: Târgu-Mureş
country: Romania
facility: Targu Mures
city: Barcelona
country: Spain
facility: Barcelona
city: Madrid
country: Spain
facility: Madrid
city: Madrid
country: Spain
facility: Madrid
city: Santiago De Compostela
country: Spain
facility: Santiago de Compostela ( Coruña )
city: Valencia
country: Spain
facility: Valencia
city: Valencia
country: Spain
facility: Valencia
Study officials:
affiliation: Tectonic Therapeutic
name: Robert Rogers, MD
role: STUDY_DIRECTOR
References: