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

NCT04712669 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: RVT-1201-2002 / ELEVATE 2
• Study Type: interventional
• Target: 108
• Locations: 17 countries
• Sites: 64

Brief Summary

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

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline of Pulmonary Vascular Resistance (PVR) at Week 24

  Pulmonary vascular resistance (PVR) was measured by right heart catheterization (RHC)

  24 Weeks

Secondary Outcomes (3)

• Change From Baseline in World Health Organization (WHO) Functional Class (FC)

  24 Weeks

• Change From Baseline in Six-minute Walk Distance (6MWD)

  24 Weeks

• Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Levels

  24 Weeks

Study Arms (8)

Rodatristat Ethyl 300 mg BID

EXPERIMENTAL

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

Drug: rodatristat ethyl 300 mg tablet BID

Rodatristat Ethyl 600 mg BID

EXPERIMENTAL

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

Drug: rodatristat ethyl 600 mg BID

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Placebo-Rodatristat Ethyl 300 mg

EXPERIMENTAL

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

Drug: rodatristat ethyl 300 mg tablet BID

Placebo-Rodatristat Ethyl 600 mg

EXPERIMENTAL

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

Drug: rodatristat ethyl 600 mg BID

Rodatristat Ethyl 300 mg-Rodatristat Ethyl 300 mg

EXPERIMENTAL

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

Drug: rodatristat ethyl 300 mg tablet BID

Rodatristat Ethyl 300 mg-Rodatristat Ethyl 600 mg

EXPERIMENTAL

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

Drug: rodatristat ethyl 600 mg BID

Rodatristat Ethyl 600 mg-Rodatristat Ethyl 600 mg

EXPERIMENTAL

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

Drug: rodatristat ethyl 600 mg BID

Interventions

rodatristat ethyl 300 mg tablet BID DRUG

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

Placebo-Rodatristat Ethyl 300 mg; Rodatristat Ethyl 300 mg BID; Rodatristat Ethyl 300 mg-Rodatristat Ethyl 300 mg

rodatristat ethyl 600 mg BID DRUG

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

Placebo-Rodatristat Ethyl 600 mg; Rodatristat Ethyl 300 mg-Rodatristat Ethyl 600 mg; Rodatristat Ethyl 600 mg BID; Rodatristat Ethyl 600 mg-Rodatristat Ethyl 600 mg

Placebo DRUG

2 matching placebo tablets on top of standard of care

Placebo

Eligibility Criteria

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

You may qualify if:

• \. 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:
• Connective tissue disease
• Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening
• Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows:
• stable treatment with HIV medications for at least 8 weeks prior to Screening
• no active opportunistic infection during the Screening Period
• no hospitalizations due to HIV for at least 4 weeks prior to Screening
• WHO FC II or III
• Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization:
• mPAP of \>20 mmHg
• PVR ≥ 350 dyne•sec/cm5
• 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
• MWD of 100 to 550 meters at Screening
• 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.

You may not qualify if:

• Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception
• 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)
• PH associated with significant venous or capillary involvement (PCWP \> 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD)
• Three or more of the following risk factors for left ventricular disease:
• BMI \> 30 kg/m2
• Diagnosis of essential hypertension that is actively treated
• Diabetes mellitus
• 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)
• Atrial fibrillation
• Left atrial volume index \> 41 mL/m2 \[or left atrial diameter (LA) \> 4 cm if LAVi unavailable\]
• Known genetic hypertrophic cardiomyopathy
• Known cardiac sarcoidosis or amyloidosis
• The patient has a history of, or currently has, a constrictive cardiomyopathy.
• 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).
• Hemodynamically significant valvular heart disease as determined by the Investigator, including:

Sponsors & Collaborators

• Altavant Sciences GmbH: lead

Study Sites (64)

Arizona Pulmonary Specialists

Phoenix, Arizona, 85012, United States

Location

University of California San Diego Health Sciences

La Jolla, California, 92093, United States

Location

VA Greater LA Healthcare System/UCLA

Los Angeles, California, 90073, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95816, United States

Location

Jeffrey S. Sager, MD Medical Corporation

Santa Barbara, California, 93105, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

George Washington University Medical Center

Washington D.C., District of Columbia, 20037, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Norton Pulmonary Specialists

Louisville, Kentucky, 40202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of New Mexico Heath Science Center

Albuquerque, New Mexico, 87106, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

University of Rochester

Rochester, New York, 14623, United States

Location

University of North Carolina Medical Center - Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Physicians

Cincinnati, Ohio, 45219, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Brown University - Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042-3307, United States

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, 4020, Austria

Location

AKH- Wien, Medizinische Univsersität Wien

Vienna, 1090, Austria

Location

Hôpital Erasme

Brussels, Brussels Capital, 1070, Belgium

Location

UZ Leuven - Campus Gasthuisberg - Pneumologie

Leuven, Vlaams Brabant, 3000, Belgium

Location

University Clinical Centre of the Republic of Srpska

Banja Luka, 78 000, Bosnia and Herzegovina

Location

University Clinical Hospital Mostar

Mostar, 88000, Bosnia and Herzegovina

Location

University MHAT "Sv. Anna"

Sofia, Sofia-Grad, 1750, Bulgaria

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y6J4, Canada

Location

London Health Sciences Centre - Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Fakultni nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

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

Caen, Calvados, 14033, France

Location

Groupement Hospitalier Est

Lyon, Rhône, 69677, France

Location

Chu De Bicetre

Le Kremlin-Bicêtre, Val-de-Marne, 94275, France

Location

CHU de Saint-Etienne - Hopital Nord

Saint-Etienne, 42270, France

Location

Universitätsklinikum Giessen und Marburg

Giessen, 35392, Germany

Location

Umberto I Policlinico di Roma, Università La Sapienza

Rome, Roma, 00161, Italy

Location

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

Genova, 16132, Italy

Location

IRCCS Policlinico San Matteo, Università degli studi di Pavi

Pavia, 27100, Italy

Location

P.Stradina Clinical University Hospital

Riga, LV-1002, Latvia

Location

Spitalul Clinic Republican

Chisinau, MD2025, Moldova

Location

Wojewodzki Specjalistyczny Szpital im. dr Wl. Bieganskiego

Lodz, Lódzkie, 91-347, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15-276, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, 20-954, Poland

Location

Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina

Otwock, 05-400, Poland

Location

Institute for Cardiovascular diseases of Vojvodina

Kamenitz, Vojvodina, 21204, Serbia

Location

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, Vojvodina, 21204, Serbia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Dnipropetrovsk Regional Clinical Diagnostic Center

Dnipro, Dnipropetrovsk Oblast, 49070, Ukraine

Location

Nats Naukovyi Tsentr Amn Ukrainy

Kyiv, 03680, Ukraine

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39307144 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

rodatristat; BID protein, human

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Ravi Grewal
• Organization: Sumitomo Pharma America

ravi.grewal@us.sumitomo-pharma.com

+1 (508) 481-6700

Study Officials

• Howard M Lazarus, MD, FCCP

  Altavant Sciences GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Following screening assessments, Patients will be enrolled into 1 of 3 treatment arms in a core double blind phase in 1:1:1 randomization. Subjects are allowed to participant into open label extension phase upon completion of double blind phase.

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 15, 2021
• Study Start: March 15, 2021
• Primary Completion: June 5, 2023
• Study Completion: August 28, 2023
• Last Updated: June 4, 2025
• Results First Posted: June 4, 2025

Record last verified: 2025-06

Locations

FR (4); CA (4); GB (2); US (28); AU (2); ES (2); LA (1); IT (3); PL (4); BE (2); BU (1); CZ (2); DE (1); SE (3); UA (2); BO (2); MO (1)