A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (Core OLE)

NCT ID: NCT04712669

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-15
• Study Completion Date: 2023-08-28

Brief Summary

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

Detailed Description

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.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rodatristat Ethyl 300 mg BID

MAIN study: Rodatristat ethyl 300 mg and placebo tablet BID + standard of care medication(s) taken for 24 weeks

Group Type: EXPERIMENTAL

rodatristat ethyl 300 mg tablet BID

Intervention Type: DRUG

rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care

Rodatristat Ethyl 600 mg BID

MAIN study:Rodatristat ethyl two 300 mg tablets BID + standard of care medication(s) taken for 24 weeks

Group Type: EXPERIMENTAL

rodatristat ethyl 600 mg BID

Intervention Type: DRUG

2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care

Placebo

MAIN study: Matching two placebo tablets BID+ standard of care medication(s) taken for 24 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2 matching placebo tablets on top of standard of care

Placebo-Rodatristat Ethyl 300 mg

Subjects whose actual treatment group is Placebo in the double-blind phase (Main Study) and received Rodatristat ethyl two 300 mg tablets BID in the open-label phase

Group Type: EXPERIMENTAL

rodatristat ethyl 300 mg tablet BID

Intervention Type: DRUG

rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care

Placebo-Rodatristat Ethyl 600 mg

Subjects whose actual treatment group is Placebo in the double-blind phase (Main Study) and received Rodatristat ethyl two 600 mg tablets BID in the open-label phase

Group Type: EXPERIMENTAL

rodatristat ethyl 600 mg BID

Intervention Type: DRUG

2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care

Rodatristat Ethyl 300 mg-Rodatristat Ethyl 300 mg

Subjects whose actual treatment group is Rodatristat ethyl two 300 mg in the double-blind phase (Main Study) and received Rodatristat ethyl two 300 mg tablets BID in the open-label phase

Group Type: EXPERIMENTAL

rodatristat ethyl 300 mg tablet BID

Intervention Type: DRUG

rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care

Rodatristat Ethyl 300 mg-Rodatristat Ethyl 600 mg

Subjects whose actual treatment group is Rodatristat ethyl two 300 mg in the double-blind phase (Main Study) and received Rodatristat ethyl two 600 mg tablets BID in the open-label phase

Group Type: EXPERIMENTAL

rodatristat ethyl 600 mg BID

Intervention Type: DRUG

2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care

Rodatristat Ethyl 600 mg-Rodatristat Ethyl 600 mg

Subjects whose actual treatment group is Rodatristat ethyl two 600 mg in the double-blind phase (Main Study) and received Rodatristat ethyl two 600 mg tablets BID in the open-label phase

Group Type: EXPERIMENTAL

rodatristat ethyl 600 mg BID

Intervention Type: DRUG

2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care

Interventions

rodatristat ethyl 300 mg tablet BID

rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care

Intervention Type: DRUG

rodatristat ethyl 600 mg BID

2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care

Intervention Type: DRUG

Placebo

2 matching placebo tablets on top of standard of care

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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:

a. Idiopathic PAH b. Heritable PAH c. Drug- or toxin-induced d. PAH associated with:

1. Connective tissue disease

2. Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening

3. Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows:

1. stable treatment with HIV medications for at least 8 weeks prior to Screening

2. no active opportunistic infection during the Screening Period

3. no hospitalizations due to HIV for at least 4 weeks prior to Screening

4. WHO FC II or III

5. Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization:

1. mPAP of >20 mmHg

2. PVR ≥ 350 dyne•sec/cm5

3. 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

6. 6MWD of 100 to 550 meters at Screening

7. 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.

8. 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):

1. Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal, and

2. 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

9. 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.

Exclusion Criteria

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:

1. BMI > 30 kg/m2

2. Diagnosis of essential hypertension that is actively treated

3. Diabetes mellitus

4. 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)

5. Atrial fibrillation

6. Left atrial volume index > 41 mL/m2 [or left atrial diameter (LA) > 4 cm if LAVi unavailable]

5. Known genetic hypertrophic cardiomyopathy

6. Known cardiac sarcoidosis or amyloidosis

7. The patient has a history of, or currently has, a constrictive cardiomyopathy.

8. 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).

9. Hemodynamically significant valvular heart disease as determined by the Investigator, including:

1. greater than mild aortic and/or mitral stenosis and/or

2. severe mitral and/or aortic regurgitation (> Grade 3)

10. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Altavant Sciences GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Howard M Lazarus, MD, FCCP

Role: STUDY_DIRECTOR

Altavant Sciences GmbH

Locations

Arizona Pulmonary Specialists

Phoenix, Arizona, United States

University of California San Diego Health Sciences

La Jolla, California, United States

VA Greater LA Healthcare System/UCLA

Los Angeles, California, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

Jeffrey S. Sager, MD Medical Corporation

Santa Barbara, California, United States

University of Colorado

Aurora, Colorado, United States

George Washington University Medical Center

Washington D.C., District of Columbia, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

The University of Kansas Medical Center

Kansas City, Kansas, United States

Norton Pulmonary Specialists

Louisville, Kentucky, United States

Tufts Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital (BWH), Harvard Medical School

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of New Mexico Heath Science Center

Albuquerque, New Mexico, United States

NYU Langone Health

New York, New York, United States

University of Rochester

Rochester, New York, United States

University of North Carolina Medical Center - Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati Physicians

Cincinnati, Ohio, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Brown University - Rhode Island Hospital

Providence, Rhode Island, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

UT Southwestern

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, Austria

AKH- Wien, Medizinische Univsersität Wien

Vienna, , Austria

Hôpital Erasme

Brussels, Brussels Capital, Belgium

UZ Leuven - Campus Gasthuisberg - Pneumologie

Leuven, Vlaams Brabant, Belgium

University Clinical Centre of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

University Clinical Hospital Mostar

Mostar, , Bosnia and Herzegovina

University MHAT "Sv. Anna"

Sofia, Sofia-Grad, Bulgaria

Peter Lougheed Centre

Calgary, Alberta, Canada

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, Canada

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Centre Hospitalier Universitaire (CHU) de Caen - Hopital Cote de Nacre

Caen, Calvados, France

Groupement Hospitalier Est

Lyon, Rhône, France

Chu De Bicetre

Le Kremlin-Bicêtre, Val-de-Marne, France

CHU de Saint-Etienne - Hopital Nord

Saint-Etienne, , France

Universitätsklinikum Giessen und Marburg

Giessen, , Germany

Umberto I Policlinico di Roma, Università La Sapienza

Rome, Roma, Italy

AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can

Genova, , Italy

IRCCS Policlinico San Matteo, Università degli studi di Pavi

Pavia, , Italy

P.Stradina Clinical University Hospital

Riga, , Latvia

Spitalul Clinic Republican

Chisinau, , Moldova

Wojewodzki Specjalistyczny Szpital im. dr Wl. Bieganskiego

Lodz, Lódzkie, Poland

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, , Poland

Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina

Otwock, , Poland

Institute for Cardiovascular diseases of Vojvodina

Kamenitz, Vojvodina, Serbia

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, Vojvodina, Serbia

Clinical Center of Serbia

Belgrade, , Serbia

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Dnipropetrovsk Regional Clinical Diagnostic Center

Dnipro, Dnipropetrovsk Oblast, Ukraine

Nats Naukovyi Tsentr Amn Ukrainy

Kyiv, , Ukraine

Royal Free London NHS Foundation Trust

London, , United Kingdom

Royal Brompton Hospital

London, , United Kingdom

Countries

United States; Austria; Belgium; Bosnia and Herzegovina; Bulgaria; Canada; Czechia; France; Germany; Italy; Latvia; Moldova; Poland; Serbia; Spain; Ukraine; United Kingdom

References

Sitbon O, Skride A, Feldman J, Sahay S, Shlobin OA, McLaughlin V, Ghofrani HA, Langleben D, Parsley E, D'Souza G, Marmon T, Kamau-Kelley W, Jones R, Grewal R, Wring S, Palacios M, Naik H, Denning J, Lazarus HM, Humbert M. Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial. Lancet Respir Med. 2024 Nov;12(11):865-876. doi: 10.1016/S2213-2600(24)00226-1. Epub 2024 Sep 19.

Reference Type: DERIVED

PMID: 39307144 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RVT-1201-2002 / ELEVATE 2

Identifier Type: -

Identifier Source: org_study_id