Pulmonary Arterial Hypertension (PAH)Phase 2ATHENANCT07601295
Tiprelestat Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)
A Phase 2 study testing Tiprelestat (5 mg) and Tiprelestat (10 mg) in people with Pulmonary Arterial Hypertension (PAH), run by Stanford University at 10 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Arterial Hypertension (PAH)
- What is being tested?
- Tiprelestat (5 mg) and Tiprelestat (10 mg)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 10 sitesUnited States
- Study dates
- Jul 2026to Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults age 18 to 75 years.
- 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.
- Diagnosis of WHO Group I PAH.
- 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).
- 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.
- 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.
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- 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).
- 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.
- 6MWD ≥100 and ≤500 meters at screening.
- Willing to adhere to study restrictions and examination schedule.
Who cannot join
- Diagnosis of WHO Group 2 - 5 Pulmonary Hypertension.
- Participation in another clinical trial, or experimental use, involving a PAH investigational drug or device within the last 3 months.
- 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.
- FEV1 / FVC < 70% predicted and FEV1 < 60% predicted.
- Significant left-sided heart disease (based on screening Echocardiogram):
- Moderate or severe aortic or mitral valve disease
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- Diastolic dysfunction ≥ Grade II
- LV systolic function < 45%
- Pericardial constriction
- Restrictive cardiomyopathy
- Significant coronary disease with demonstrable ischemia
- Chronic renal insufficiency defined as an estimated creatinine clearance < 30 ml/min.
- Current atrial arrhythmias not under optimal control.
- Uncontrolled systemic hypertension: SBP > 160 mmHg or DBP > 100mmHg.
- Severe hypotension: SBP < 80 mmHg.
- Pregnant or breast-feeding.
- Psychiatric, addictive, or other disorders that compromise the patient's ability to provide informed consent, to follow study protocol, and adhere to treatment instructions.
- Known allergy or hypersensitivity to tiprelestat.
- Moderate to severe hepatic dysfunction with a Child Pugh score >10.
- Hyperkalemia defined as Potassium > 5.1 mEq/L at screening.
- 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.
- 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.
- 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).
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites
University of Colorado (UCD) Anschutz
Aurora, Colorado, 80045
Harvard University / Brigham and Women's Hospital
Boston, Massachusetts, 02138
University of Texas Southwestern
Dallas, Texas, 75390
Duke University
Durham, North Carolina, 27710
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brown University/Rhode Island Hospital
Providence, Rhode Island, 02904
University of California, San Francisco
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
Stanford University
Stanford, California, 94305
The University of Arizona / Banner University Medical Center
Tucson, Arizona, 85719
About this study
Official title: 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).
- Conditions
- Pulmonary Arterial Hypertension (PAH)
- Being tested
- Tiprelestat (5 mg), Placebo (1 mL 0.9% saline solution), Tiprelestat (10 mg)
- Keywords
- tiprelestat, elafin, pulmonary arterial hypertension, PAH
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tiprelestat (5 mg)Drug
Also called Elafin
5 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days.
Placebo (1 mL 0.9% saline solution)Drug
Matching 1 mL 0.9% saline solution administered as a daily subcutaneous injection for 168 days.
Tiprelestat (10 mg)Drug
Also called Elafin
10 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days.
| Study group | Role | What they receive |
|---|---|---|
| Tiprelestat (5 mg) | Experimental | Participants receive tiprelestat injection daily for 168 days. Receives: Drug: Tiprelestat (5 mg) |
| Tiprelestat (10 mg) | Experimental | Participants receive tiprelestat injection daily for 168 days. Receives: Drug: Tiprelestat (10 mg) |
| Placebo (1 mL 0.9% saline solution) | Placebo comparator | Participants receive placebo injection (matching tiprelestat) daily for 168 days. Receives: Drug: Placebo (1 mL 0.9% saline solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary Vascular Resistance (PVR)
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.
Measured: Baseline to week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2026
- Study startJul 2026 (estimated)
- Primary completionFeb 2030 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial Hypertension (PAH)Studies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roham T. Zamanian, Stanford University
- Investigators
- Roham T Zamanian, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07601295
- Sponsor's protocol ID
- 84755
- Other IDs
- UG3HL180990, U24HL180994
- Acronym
- ATHENA
- Status last verified
- May 2026
- First submitted
- 15 May 2026
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07601295
- Acronym / sponsor ID
- ATHENA / 84755
- Conditions
- Pulmonary Arterial Hypertension (PAH)
- Keywords
- tiprelestat, elafin, pulmonary arterial hypertension, PAH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), University of Michigan
- Study start
- Jul 2026 (estimated)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Mar 2030 (estimated)
- First posted
- 22 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tiprelestat (5 mg) | Experimental | Drug: Tiprelestat (5 mg)Participants receive tiprelestat injection daily for 168 days. |
| Tiprelestat (10 mg) | Experimental | Drug: Tiprelestat (10 mg)Participants receive tiprelestat injection daily for 168 days. |
| Placebo (1 mL 0.9% saline solution) | Placebo comparator | Drug: Placebo (1 mL 0.9% saline solution)Participants receive placebo injection (matching tiprelestat) daily for 168 days. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults age 18 to 75 years.
- 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.
- Diagnosis of WHO Group I PAH.
- 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).
- 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.
Key exclusion criteria (23 listed)
- Diagnosis of WHO Group 2 - 5 Pulmonary Hypertension.
- Participation in another clinical trial, or experimental use, involving a PAH investigational drug or device within the last 3 months.
- 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.
- FEV1 / FVC < 70% predicted and FEV1 < 60% predicted.
- Significant left-sided heart disease (based on screening Echocardiogram):
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tiprelestat (5 mg)Also: Elafin5 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days. | Drug | Tiprelestat (5 mg) |
| Placebo (1 mL 0.9% saline solution)Matching 1 mL 0.9% saline solution administered as a daily subcutaneous injection for 168 days. | Drug | Placebo (1 mL 0.9% saline solution) |
| Tiprelestat (10 mg)Also: Elafin10 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days. | Drug | Tiprelestat (10 mg) |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roham T Zamanian, MD principal investigator
Stanford University
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tiprelestat (5 mg) and Tiprelestat (10 mg) in people with Pulmonary Arterial Hypertension (PAH), run by Stanford University at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pulmonary Vascular Resistance (PVR) (time frame: Baseline to week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.