Tiprelestat Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH) (ATHENA)

May 15, 2026 updated by: Roham T. Zamanian, Stanford University

A Phase II, Randomized, Double-Blind, Safety and Efficacy Study of Tiprelestat Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)

The primary objective of this study is to compare the efficacy, safety, and tolerability of tiprelestat plus Standard of Care (SOC) compared with placebo plus SOC in patients with World Health Organization (WHO) functional class II-IV pulmonary arterial hypertension (PAH).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • The University of Arizona / Banner University Medical Center
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
      • Stanford, California, United States, 94305
        • Stanford University
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado (UCD) Anschutz
    • Massachusetts
      • Boston, Massachusetts, United States, 02138
        • Harvard University / Brigham and Women's Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Rhode Island
      • Providence, Rhode Island, United States, 02904
        • Brown University/Rhode Island Hospital
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults age 18 to 75 years.
  2. Willingness to give written informed consent prior to any study-related procedures being performed and to be able to adhere to the study restrictions and examination schedule.
  3. Diagnosis of WHO Group I PAH.
  4. WHO functional class II - IV despite optimized treatment SOC, with 1 or more modalities including phosphodiesterase 5 (PDE5) inhibitor, soluble guanylate cyclase stimulator (sGCS), endothelin receptor antagonist (ERA), and/or a prostacyclin analogue or receptor agonist (SC/inhaled/PO) (see #5), as well as Sotatercept (see #6).
  5. On stable doses of PDE5 inhibitor, ERA, sGCS, or prostacyclin analogue/receptor agonist for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of baseline dose during the duration of the study is allowed per medical practice.
  6. On stable doses of Sotatercept therapy for at least 6 months prior to screening, and intended to be continued during the duration of the study.
  7. Screening right heart catheterization mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest; pulmonary wedge pressure (PAWP) ≤ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg; AND pulmonary vascular resistance (PVR) ≥ 400 dynes•sec/cm5 (5 Wood Units).
  8. If participant is of childbearing potential, willing to use adequate methods of contraception throughout the course of the study. If participant is of childbearing potential (a participant < 55 years of age who has not been postmenopausal for ≥ 5 years or who has not had a bilateral salpingectomy, hysterectomy and/or oophorectomy), need to employ two reliable means of contraception which may include surgical sterilization, barrier methods, spermicidals, intrauterine devices, and/or hormonal contraception, unless the participant chooses abstinence (to avoid heterosexual intercourse completely). If a participant chooses abstinence, then a second reliable means of contraception is not needed.
  9. 6MWD ≥100 and ≤500 meters at screening.
  10. Willing to adhere to study restrictions and examination schedule.

Exclusion Criteria:

  1. Diagnosis of WHO Group 2 - 5 Pulmonary Hypertension.
  2. Participation in another clinical trial, or experimental use, involving a PAH investigational drug or device within the last 3 months.
  3. Total lung capacity (TLC) < 60% predicted; if TLC is ≥ 60% and < 70% predicted, high resolution computed tomography (HRCT) must be available to exclude significant interstitial lung disease.
  4. FEV1 / FVC < 70% predicted and FEV1 < 60% predicted.

  5. Significant left-sided heart disease (based on screening Echocardiogram):

    1. Moderate or severe aortic or mitral valve disease
    2. Diastolic dysfunction ≥ Grade II
    3. LV systolic function < 45%
    4. Pericardial constriction
    5. Restrictive cardiomyopathy
    6. Significant coronary disease with demonstrable ischemia
  6. Chronic renal insufficiency defined as an estimated creatinine clearance < 30 ml/min.
  7. Current atrial arrhythmias not under optimal control.
  8. Uncontrolled systemic hypertension: SBP > 160 mmHg or DBP > 100mmHg.
  9. Severe hypotension: SBP < 80 mmHg.
  10. Pregnant or breast-feeding.
  11. Psychiatric, addictive, or other disorders that compromise the patient's ability to provide informed consent, to follow study protocol, and adhere to treatment instructions.
  12. Known allergy or hypersensitivity to tiprelestat.
  13. Moderate to severe hepatic dysfunction with a Child Pugh score >10.
  14. Hyperkalemia defined as Potassium > 5.1 mEq/L at screening.
  15. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to screening or planned during the study. Subjects who are already stable in the maintenance phase of an exercise program which will continue for the duration of the study are eligible.
  16. Known active infection requiring antibiotic, antifungal, or antiviral therapies. Patients may be rescreened at physician discretion after the resolution of infection and discontinuation of antibiotic, antifungal, or antiviral therapies.
  17. Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems, other comorbidities expected to alter the patient's clinical course (i.e. active cancer; >3 comorbidities e.g., obesity, systemic HTN, diabetes).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tiprelestat (5 mg)
Participants receive tiprelestat injection daily for 168 days.
Drug: Tiprelestat (5 mg)
5 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days.
Other Names:
  • Elafin
Experimental: Tiprelestat (10 mg)
Participants receive tiprelestat injection daily for 168 days.
Drug: Tiprelestat (10 mg)
10 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days.
Other Names:
  • Elafin
Placebo Comparator: Placebo (1 mL 0.9% saline solution)
Participants receive placebo injection (matching tiprelestat) daily for 168 days.
Drug: Placebo (1 mL 0.9% saline solution)
Matching 1 mL 0.9% saline solution administered as a daily subcutaneous injection for 168 days.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Pulmonary Vascular Resistance (PVR)
Time Frame: Baseline to week 24
PVR is calculated based on direct measurements during the right heart catheterization (RHC) procedure. PVR = (mPAP - PAWP) / CO, where mPAP is the mean pulmonary artery pressure, PAWP is the pulmonary wedge arterial pressure, and CO is the cardiac output. These cardiac measures are also obtained from right heart catheterization. PVR is measured in Wood units (WU) or dynes (dynes*sec/cm5), and higher values are associated with more severe disease. Normal range for PVR is 1-3 WU (80-240 dynes*sec/cm5) and can be as high as 30 WU (2,400 80-240 dynes*sec/cm5) in disease.
Baseline to week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
University of Michigan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Roham T Zamanian, MD, Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 15, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 22, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 84755
  • UG3HL180990 (U.S. NIH Grant/Contract)
  • U24HL180994 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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