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

Tectonic Therapeutic

Status and phase: Enrolling; Phase 2

Conditions: Heart Failure With Preserved Ejection Fraction; Pulmonary Hypertension

Treatments: Drug: TX000045- Dose A; Drug: TX000045- Dose B; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06616974

TX000045-003

Details and patient eligibility

About

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).

Full 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

Enrollment: 180 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Is a male or female of non-childbearing potential between the ages of 18 and 80 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 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 metersquare;
   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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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180 participants in 3 patient groups, including a placebo group

TX000045 Dose A

Experimental group

Description:

Participants will receive a single dose of TX000045 Dose A subcutaneously every 2 weeks for 24 weeks from Day 1 to Day 155.

Treatment:

Drug: TX000045- Dose A

TX000045 Dose B

Experimental group

Description:

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.

Treatment:

Drug: TX000045- Dose B

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo