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)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 191
- 试验地点
- 116
- 主要终点
- Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.
研究概览
简要总结
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).
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 83 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group
- •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 TX
- •Is pregnant or breastfeeding.
- •Has a history of cancer within 5 years of screening other than basal cell carcinoma, cervical carcinoma, or squamous cell carcinomas of the skin.
- •Has a history of drug or alcohol abuse.
- •Was recently dosed in any clinical research study.
研究组 & 干预措施
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.
干预措施: TX000045- Dose A (Drug)
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.
干预措施: TX000045- Dose B (Drug)
Placebo
Participants will receive a single placebo dose SC for 24 weeks from Day 1 to Day 155
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.
时间窗: Baseline up to Week 30 post first dose
Assess safety of TX000045 by the incidence of adverse events, adverse events of special interest and SAEs.
时间窗: Baseline up to Week 30 post first dose
Number of participants with treatment-related adverse events.
时间窗: Baseline up to Week 30 post first dose
Number of participants with changes in the physical examination findings.
时间窗: 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).
时间窗: Baseline up to Week 24 post first dose
Measured by right heart catheterization (RHC) between those who received TX000045 and those with placebo.
次要结局
- 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 mean pulmonary arterial pressure (mPAP) for all participants and in participants with CpcPH.(Baseline to Week 24 post first dose)
- 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 responses on the Kansas City Cardiomyopathy Questionnaire (KCCQ) for all participants and in participants with CpcPH.(Baseline to Week 24 post first dose)
- Mean change from baseline in pulmonary capillary wedge pressure (PCWP).(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 PVR for all participants.(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 mean pulmonary arterial pressure (mPAP) for all participants and in participants with CpcPH.(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)
- Mean change from baseline in total pulmonary resistance (TPR) for all participants and in participants with CpcPH.(Baseline to Week 24 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)
- 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)