Heart Failure With Preserved Ejection Fraction, Pulmonary Hypertension
Conditions
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 191 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
Interventions
DRUGTX000045- Dose A
The participants will receive a subcutaneous injection of Dose A of TX000045 every 2 weeks for 24 weeks.
DRUGTX000045- 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.
DRUGPlacebo
The participants will receive a subcutaneous injection of placebo every 2 weeks for 24 weeks.
Sponsors
Tectonic Therapeutic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 83 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 | — |
| 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 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. |
| 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 | — |
| 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 | — |
Countries
Armenia, Australia, Austria, Belgium, Bulgaria, Georgia, Germany, Latvia, Moldova, New Zealand, Poland, Portugal, Romania, Serbia, Spain, Ukraine, United States
Contacts
STUDY_DIRECTORRobert Rogers, MD
Tectonic Therapeutic
Outcome results
None listed