TEPH: Telaglenastat Efficacy in Pulmonary Hypertension

NCT07223528 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY24070041
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The research study is being conducted to evaluate the effectiveness of a drug called Telaglenastat in adults diagnosed with Pulmonary Hypertension (PH). PH is a progressive condition that affects the arteries in the lungs, specifically the pulmonary arteries, which carry blood from the right side of the heart to the lungs. Telaglenastat is not currently approved by the Food and Drug Administration for the treatment of PH. However, the study investigators believe that Telaglenastat may help lower blood pressure in the lungs and improve both heart and lung function. It is important to note that the drug will not be available to participants once the study concludes.

Conditions

Pulmonary Hypertension

Keywords

pulmonary hypertension; lung disease; telaglenastat

Outcome Measures

Primary Outcomes (1)

• Pulmonary Vascular Resistance (PVR) measured via Right Hearth Catheterization (RHC)

  We will use PVR to measure the effect of treatment on PH

  Visit 2 at week 1 and Visit 7 at week 12

Secondary Outcomes (4)

• Functional class (FC)

  The functional class will be determined at week 1 and 12

• 6 minute walk test

  6MWT will be at week 1 and 12

• NT-proBNP

  Will be measure at week 1 and 12

• Glutamine and glutamate plasma levels

  Will be done on screening visit, on week 1 and week 12

Study Arms (1)

Open-Label Telaglenastat Arm

EXPERIMENTAL

Drug: Telaglenastat

Interventions

Telaglenastat DRUG

The participant will need to come in for a screening visit prior prescribing the medication to confirm eligibility. The visit will include physical exams, labs, right heart cath, and maybe pulmonary function test and chest imaging. Eligible participants will be taking 800 mg Telaglenastat (CB-839) by mouth with food twice a day for a total of 12 weeks. Participants will need to come in for study related visits during this time. At the end of 12 months period, we will need to repeat same activities we did prior to prescribing to medication. Pending FDA approval, eligible participants may continue Telaglenastat for an additional 12 weeks.

Open-Label Telaglenastat Arm

Eligibility Criteria

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

You may qualify if:

• Male or female age 18-75 years old.
• Able to provide written informed consent.
• Able to comply with study procedures, able to undergo cardiac catheterization and exercise testing.
• Patients will be identified with PH Group 1-4 PH by an expert clinician in the UPMC Comprehensive Care Center for Pulmonary Hypertension.
• For Group 1, 3, and 4 PH, prior right heart catheterization (RHC) should show documented diagnosis of precapillary PH at mean pulmonary arterial pressure (mPAP \> 20 mm Hg, PCWP \< 15 mm Hg, and PVR \> 4 WU) within 1 year of randomization. If patient doesn't have RHC within 1 year, we will repeat RHC at baseline visit. For Group 2 PH, prior right heart catheterization (RHC) should show mean pulmonary arterial pressure mPAP \> 20 mm Hg and PVR \> 4 WU within one year of randomization. If patient don't have RHC within 1 year we will repeat RHC at baseline visit.
• Minimum pulmonary vascular resistance (PVR) of \> 4 Wood units by RHC at screening within last 6 months on at least one month of stable medical therapy.
• Symptomatic PH classified as WHO functional class II or III.
• Body mass index (BMI) 18 to 40 kg/m² at Screening. If BMI is \> 35 kg/m², subject chest circumference should be \< 65 inches (165 cm).
• minute walk distance (6MWD) ≥ 100 meters (m) and \< 550 m at screening.
• For Group 1 PH, patients on SOC medical treatment for PH with vasodilators or Sotatercept are required to have been receiving a stable dose for at least 3 months before undergoing randomization.
• For Group 2 PH-HFpEF: Documented transthoracic echocardiogram or cardiac MRI with LV ejection fraction \> 50% within 6 months of enrollment, along with meeting at least one of the three criteria by echocardiographic/MRI: (1) Diastolic dysfunction, (2) Left atrial enlargement (LA diameter \> 3.6 cm), or (3) Prior right heart catheterization data indicating PCWP \> 15 mm Hg. Stable heart failure therapy for at least 30 days.
• For Group 3 PH-ILD, documented diagnosis of interstitial lung disease (diffuse parenchymal lung disease) by high resolution lung CT scan within 6 months of randomization. Patients with Group 3 PH with connective tissue disease should have confirmed baseline FVC \< 70% within 6 months of randomization. For subjects with a history of lobectomy or pneumonectomy, and for whom there are no population-based normalization methods, assessment based on residual lung volume will be permitted to assess eligibility. Patients receiving drug treatment (i.e., pirfenidone or nintedanib) for their underlying lung disease or pulmonary hypertension (i.e., inhaled Treprostinil) should receive a stable dose for at least 30 days before undergoing randomization.
• For Group 4 PH (CTEPH) eligible patients will have V/Q scan or CT scan with contrast demonstrating chronic thromboembolic disease in the pulmonary vasculature at least 6 months after most recent pulmonary embolus and with right heart catheterization within one year of enrollment. If patient doesn't have RHC within 1 year, we will repeat RHC at baseline visit. Eligible patients will include those with inoperable CTEPH or at least 6 months post-surgery with persistent thromboembolic disease. Patients receiving approved therapies for pulmonary hypertension are required to have been receiving a stable dose for at least 30 days before undergoing randomization.
• Women of childbearing potential must be willing and able to practice medically acceptable effective contraception during the study and continuing contraception for 30 days after their last dose of study drug. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile must also agree to use contraception.

You may not qualify if:

• For Group 2 PH-HFpEF patients:
• With clinically decompensated heart failure
• Uncontrolled hypertension (SBP \> 160 mm Hg, DBP \> 90)
• Echocardiographic/MRI
• Evidence of moderate-severe mitral regurgitation or mitral stenosis within 6 months of enrollment
• Group 3 PH-ILD, patients receiving approved therapies other than inhaled Treprostinil for PAH within 60 days before randomization are not eligible for enrollment.
• Group 1 PH, patients naïve to medical treatment for PH are not eligible for enrollment.
• History of lung reduction surgery or likely to undergo lung transplantation within the next 6 months.
• Enrolled in, or planned participation in, device or other interventional clinical studies or cardio-pulmonary rehabilitation programs, based upon exercise within 90 days of Screening or during study participation.
• Patients with other secondary causes of PH including, but not limited to, left or right heart failure, valvular heart disease, chronic obstructive lung disease, atrial septal defect with left to right shunt, and sleep apnea will be excluded if it was the primary cause of PAH.
• Diagnosed with significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
• Uncontrolled hypertension (SBP \> 160 mm Hg, DBP \> 90)
• Left ventricular ejection fraction (LVEF) \< 45%
• Adult congenital heart disease (ACHD)
• Sustained systolic blood pressure (SBP) \< 95 mmHg and/or diastolic blood pressure (DBP) \< 50 mmHg (confirmed by duplicate seated readings) on at least 3 consecutive occasions (self-monitored or office) prior to or at Screening, or overt symptomatic hypotension

Sponsors & Collaborators

• Chan, Stephen, MD, PhD: lead
• Synhale Theraputics: collaborator

Study Sites (1)

UPMC Presybeterian

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Lung Diseases

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Michael Risbano, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yassmin A Al Aaraj, MPH

CONTACT

14122668980; yaa29@pitt.edu

Michael Risbano, MD

CONTACT

14126922210; risbanomg@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 21, 2025
• First Posted: November 3, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 25, 2028
• Study Completion (Estimated): September 25, 2028
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will available starting 6 months after publication
• Access Criteria: The Comprehensive Pulmonary Hypertension Program and Comprehensive lung center shall require secondary investigators to obtain regulatory approval prior its provision of de-identified information to the secondary investigators

Locations

US (1)