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

NCT07601295 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 84755UG3HL180990U24HL180994
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 10

Brief 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).

Conditions

Pulmonary Arterial Hypertension (PAH)

Keywords

tiprelestat; elafin; pulmonary arterial hypertension; PAH

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to week 24

Study Arms (3)

Tiprelestat (5 mg)

EXPERIMENTAL

Participants receive tiprelestat injection daily for 168 days.

Drug: Tiprelestat (5 mg)

Tiprelestat (10 mg)

EXPERIMENTAL

Participants receive tiprelestat injection daily for 168 days.

Drug: Tiprelestat (10 mg)

Placebo (1 mL 0.9% saline solution)

PLACEBO COMPARATOR

Participants receive placebo injection (matching tiprelestat) daily for 168 days.

Drug: Placebo (1 mL 0.9% saline solution)

Interventions

Tiprelestat (5 mg) DRUG

5 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days.

Also known as: Elafin

Tiprelestat (5 mg)

Placebo (1 mL 0.9% saline solution) DRUG

Matching 1 mL 0.9% saline solution administered as a daily subcutaneous injection for 168 days.

Placebo (1 mL 0.9% saline solution)

Tiprelestat (10 mg) DRUG

10 mg of tiprelestat in 1 mL saline administered as a daily subcutaneous injection for 168 days.

Also known as: Elafin

Tiprelestat (10 mg)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• MWD ≥100 and ≤500 meters at screening.
• Willing to adhere to study restrictions and examination schedule.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Michigan: collaborator

Study Sites (10)

The University of Arizona / Banner University Medical Center

Tucson, Arizona, 85719, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Colorado (UCD) Anschutz

Aurora, Colorado, 80045, United States

Location

Harvard University / Brigham and Women's Hospital

Boston, Massachusetts, 02138, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University/Rhode Island Hospital

Providence, Rhode Island, 02904, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Elafin; Saline Solution

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Proteinase Inhibitory Proteins, Secretory; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Roham T Zamanian, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The James & Yvonne Wood Professor of Pulmonary Vascular Medicine; Director, Adult Pulmonary Hypertension Program; Associate Director, Vera Moulton Wall Center for Pulmonary Vascular Disease

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)