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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06616974




Registration number
NCT06616974
Ethics application status
Date submitted
19/09/2024
Date registered
27/09/2024
Date last updated
27/09/2024

Titles & IDs
Public title
A Study of TX000045 in Patients With Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction (the APEX Study)
Scientific 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)
Secondary ID [1] 0 0
TX000045-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Hypertension 0 0
Heart Failure With Preserved Ejection Fraction 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TX000045- Dose A
Treatment: Drugs - TX000045- Dose B
Treatment: Drugs - Placebo

Experimental: 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.

Experimental: 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.

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


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

Treatment: Drugs: TX000045- 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.

Treatment: Drugs: Placebo
The participants will receive a subcutaneous injection of placebo every 2 weeks for 24 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline on mean Pulmonary Vascular Resistance (PVR) in participants with pulmonary hypertension secondary to heart failure with preserved ejection fraction (PH-HFpEF)
Timepoint [1] 0 0
Baseline up to Week 24 post first dose
Primary outcome [2] 0 0
Assess safety of TX000045 by the incidence of adverse events, adverse events of special interest and SAEs.
Timepoint [2] 0 0
Baseline up to Week 30 post first dose
Primary outcome [3] 0 0
Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.
Timepoint [3] 0 0
Baseline up to Week 30 post first dose
Primary outcome [4] 0 0
Number of participants with treatment-related adverse events
Timepoint [4] 0 0
Baseline up to Week 24 post first dose
Primary outcome [5] 0 0
Number of participants with changes in the physical examination findings
Timepoint [5] 0 0
Baseline to Week 30 post first dose
Secondary outcome [1] 0 0
Effect of TX000045 on mean PVR in participants with PVR greater than or equal to 3 wood units.
Timepoint [1] 0 0
Baseline to Week 24 post first dose
Secondary outcome [2] 0 0
Mean change from baseline in 6-minute walk test (6MWT) distance.
Timepoint [2] 0 0
Baseline to Week 24 post first dose
Secondary outcome [3] 0 0
Mean change from baseline in 6-minute walk test (6MWT) distance in participants with PVR greater than or equal to 3 wood units.
Timepoint [3] 0 0
Baseline to Week 30 post first dose
Secondary outcome [4] 0 0
Change from baseline in Pulmonary capillary wedge pressure (PCWP) in patients who received TX000045 vs Placebo.
Timepoint [4] 0 0
Baseline to Week 24 post first dose
Secondary outcome [5] 0 0
Change from baseline in mean pulmonary arterial pressure (mPAP) in participants who received TX000045 vs Placebo.
Timepoint [5] 0 0
Baseline to Week 24 post first dose
Secondary outcome [6] 0 0
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) in participants with PH-HFpEF.
Timepoint [6] 0 0
Baseline to Week 30 post first dose
Secondary outcome [7] 0 0
Change from baseline responses on the Kansas City Cardiomyopathy Questionnaire (KCCQ) in participants with PH-HFpEF.
Timepoint [7] 0 0
Baseline to Week 24 post first dose
Secondary outcome [8] 0 0
Evaluate the serum concentrations of TX000045
Timepoint [8] 0 0
Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose
Secondary outcome [9] 0 0
Evaluate immunogenicity of TX000045 by antibody titers
Timepoint [9] 0 0
Day 1, Week 2, Week 4, Week 8, Week 16, Week 24 and Week 30 post first dose

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
30/09/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
20/11/2026
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS
Recruitment hospital [1] 0 0
Westmead Hospital - Macquarie
Recruitment hospital [2] 0 0
Wollongong - Wollongong
Recruitment hospital [3] 0 0
Auchenflower - Auchenflower
Recruitment hospital [4] 0 0
Chermside - Chermside
Recruitment hospital [5] 0 0
Hobart - Hobart
Recruitment postcode(s) [1] 0 0
2109 - Macquarie
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4066 - Auchenflower
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Mississippi
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Armenia
State/province [13] 0 0
Yerevan
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Pleven
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Plovdiv
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
Country [17] 0 0
Georgia
State/province [17] 0 0
Tb
Country [18] 0 0
Georgia
State/province [18] 0 0
Tbilisi
Country [19] 0 0
Germany
State/province [19] 0 0
Hamburg
Country [20] 0 0
Germany
State/province [20] 0 0
Mainz
Country [21] 0 0
Germany
State/province [21] 0 0
Remscheid
Country [22] 0 0
Moldova, Republic of
State/province [22] 0 0
Chisinau
Country [23] 0 0
New Zealand
State/province [23] 0 0
Christchurch
Country [24] 0 0
Poland
State/province [24] 0 0
Bialystok
Country [25] 0 0
Poland
State/province [25] 0 0
Kraków
Country [26] 0 0
Poland
State/province [26] 0 0
Lublin
Country [27] 0 0
Poland
State/province [27] 0 0
Lódz
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Spain
State/province [30] 0 0
Santiago De Compostela
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia
Country [32] 0 0
Turkey
State/province [32] 0 0
Gaziantep
Country [33] 0 0
Turkey
State/province [33] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Tectonic Therapeutic
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT06616974
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marcie Ruddy, MD
Address 0 0
Tectonic Therapeutic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
+1 339 337 4053
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06616974