Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Nick Kim

Description

Summary

The purpose of this study is to assess the safety and efficacy of Rodatristat Ethyl in pulmonary arterial hypertension (PAH) patients.

Official Title

A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension

Details

Rodatristat Ethyl is a peripherally restricted TPH inhibitor being studied as a potential treatment for PAH. This dose-ranging, randomized, double-blind, placebo-controlled, multicenter study will evaluate the effect of Rodatristat Ethyl from baseline on pulmonary vascular resistance as measured at right heart catheterization. Patients will be enrolled into a main study with an option to enroll into an open label extension. The study is expected to enroll patients in the USA, Canada and Europe.

Keywords

Pulmonary Arterial Hypertension, PAH, Familial Primary Pulmonary Hypertension, Hypertension, rodatristat ethyl 300 mg tablet BID, rodatristat ethyl 600 mg BID, Rodatristat Ethyl 300 mg BID

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Male and female 18 years or older 2. Body Mass Index (BMI) >18kg/m2 to <=40kg/m2 3.

Symptomatic PAH belonging to one of the following 2018 WHO Clinical Group 1 subtypes:

  1. Idiopathic PAH b. Heritable PAH c. Drug- or toxin-induced d. PAH associated with:
  2. Connective tissue disease
  3. Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening
  4. Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows:
  5. stable treatment with HIV medications for at least 8 weeks prior to Screening
  6. no active opportunistic infection during the Screening Period
  7. no hospitalizations due to HIV for at least 4 weeks prior to Screening
  8. WHO FC II or III
  9. Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization:
  10. mPAP of >20 mmHg
  11. PVR ≥ 350 dyne•sec/cm5
  12. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 350 and < 500 dyne•sec/cm5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dyne•sec/cm5
  13. 6MWD of 100 to 550 meters at Screening
  14. Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for ≥ 12 weeks prior to the screening RHC and at a stable dose level for each for ≥ 8 weeks prior to the screening RHC (see Protocol Section 6.6.2 for approved PAH medications). Any instances where doses of a medication have been missed prior to RHC must be discussed with the Medical Monitor prior to performing the RHC.
  15. Meet all of the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to Screening (performed with or without bronchodilation):
  16. Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal, and
  17. Total lung capacity (TLC) ≥ 70% of predicted normal or FVC ≥ 70% predicted if TLC is not available; For subjects with CTD associated PAH, if TLC is ≥ 60% of predicted but < 70% of predicted of if FVC ≥ 60% or predicted but < 70% of predicted, high resolution computed tomography [HRCT] obtained within 6 months of screening may be utilized to demonstrate limited interstitial lung disease
  18. If participating in an exercise program for pulmonary rehabilitation, the program must have been initiated ≥ 12 weeks prior to Screening, and patient must agree to maintain the current level of rehabilitation for the first 24 weeks of receiving IP. If not participating in an exercise training program for pulmonary rehabilitation, patient must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of receiving IP.

You CAN'T join if...

  1. Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception
  2. WHO pulmonary hypertension (PH) Group 1 PAH associated with portal hypertension or schistosomiasis; PH due to left heart disease (WHO PH Group 2), lung diseases and/or hypoxia (WHO PH Group 3), chronic thromboembolic PH (WHO PH Group 4), or PH with unclear multifactorial mechanisms (WHO PH Group 5)
  3. PH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD)
  4. Three or more of the following risk factors for left ventricular disease:
  5. BMI > 30 kg/m2
  6. Diagnosis of essential hypertension that is actively treated
  7. Diabetes mellitus
  8. History of significant coronary artery disease (e.g., chronic stable angina, history of coronary intervention within the last 3 months, or a stenosis > 70% at coronary angiography)
  9. Atrial fibrillation
  10. Left atrial volume index > 41 mL/m2 [or left atrial diameter (LA) > 4 cm if LAVi unavailable]
  11. Known genetic hypertrophic cardiomyopathy
  12. Known cardiac sarcoidosis or amyloidosis
  13. The patient has a history of, or currently has, a constrictive cardiomyopathy.
  14. Known history of any left ventricular ejection fraction (LVEF) < 40% by echocardiogram within 3 years of randomization (Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition [e.g., atrial fibrillation] is allowed).
  15. Hemodynamically significant valvular heart disease as determined by the Investigator, including:
  16. greater than mild aortic and/or mitral stenosis and/or
  17. severe mitral and/or aortic regurgitation (> Grade 3)
  18. . Severe arthritis, musculoskeletal problems, or morbid obesity that, in the opinion of the Investigator, is the cause of the patient's functional limitation and would affect the patient's ability to perform or complete the 6MWT.

Locations

  • University of California San Diego Health Sciences accepting new patients
    La Jolla California 92093 United States
  • VA Greater LA Healthcare System/UCLA accepting new patients
    Los Angeles California 90073 United States
  • Ronald Reagan UCLA Medical Center not yet accepting patients
    Los Angeles California 90095 United States

Lead Scientist at UCSD

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Altavant Sciences GmbH
ID
NCT04712669
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 90 study participants
Last Updated