Pulmonary HypertensionPhase 3RANGERNCT03068130

Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension RANGER

A Phase 3 study testing Bardoxolone methyl in people with Pulmonary Hypertension, run by Biogen at 96 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This extended access study will assess the long-term safety and tolerability of bardoxolone methyl in qualified patients with pulmonary hypertension (PH) who previously participated in controlled clinical studies with bardoxolone methyl. Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Pulmonary Hypertension
What is being tested?: Bardoxolone methyl
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 261 participants
Where: 96 sitesin 15 countries
Study dates: 18 Apr 2017to 30 Sep 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Treatment-compliant patients who are participating in qualifying ongoing studies and have completed required End-of-Treatment and/or Follow-up visits in a prior clinical study with bardoxolone methyl

Who cannot join

Participation in other investigational clinical studies involving interventional products being tested or used in a way different from the approved form or when used for an unapproved indication;
Patients who have an ongoing SAE from a clinical study that is assessed by the investigator as related to bardoxolone methyl;
Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) while taking study drug;
Women who are pregnant or breastfeeding;
Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason;
Known hypersensitivity to any component of the study drug

Trial locations and contacts

96 sites in 15 countries.

Country

City, postcode or hospital

96 sites in 15 countries

United States46 sites

University of New Mexico Health Sciences Center
Albuquerque, New Mexico, 87131
University of Michigan
Ann Arbor, Michigan, 48109
Augusta University
Augusta, Georgia, 30912
University of Colorado Denver - Division of Pulmonary Sciences
Aurora, Colorado, 80045
Piedmont-Georgia Lung
Austell, Georgia, 30106
Cedars Sinai Medical Center
Beverly Hills, California, 90211
Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Boston University School of Medicine
Boston, Massachusetts, 02118
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Illinois at Chicago
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
The Lindner Clinical Trial Center
Cincinnati, Ohio, 45219
University of Cincinnati - Department of Internal Medicine Pulmonary, Critical Care & Sleep Medicine
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27710
The Methodist Hospital Research Institute
Houston, Texas, 77030
The University of Texas - Health Science Center & Medical School at Houston
Houston, Texas, 77030
University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics
Houston, Texas, 77030
University of California San Diego
La Jolla, California, 92093
VA Healthcare System of Greater Los Angeles
Los Angeles, California, 90073
David Geffen School of Medicine UCLA
Los Angeles, California, 90095
Kentuckiana Pulmonary Associates
Louisville, Kentucky, 40202
University of Miami Miller School of Medicine
Miami, Florida, 33136
Aurora Health Care
Milwaukee, Wisconsin, 53215
Winthrop University Hospital
Mineola, New York, 11501
NYU Langone Medical Center
New York, New York, 10016
Oklahoma Heart Hospital
Oklahoma City, Oklahoma, 73120
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Banner University Medical Center, Phoenix Advanced Lung Disease Institute
Phoenix, Arizona, 85004
Arizona Pulmonary Specialists
Phoenix, Arizona, 85012
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Maine Medical Center - Division of Pulmonary and Critical Care Medicine
Portland, Maine, 04102
Oregon Health & Science University
Portland, Oregon, 97239
University of Rochester - University of Rochester Medical Center
Rochester, New York, 14642
University of California Davis Medical Center - Division of Pulmonary and Critical Care
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84132
Washington University School of Medicine
St Louis, Missouri, 63110
Harbor - UCLA Medical Center
Torrance, California, 90502
Georgetown University Medical Center - Department of Rheumatology
Washington D.C., District of Columbia, 20007
Cleveland Clinic of Florida
Weston, Florida, 33331

Other trials in United States

Japan9 sites

Chiba University Hospital
Chiba, 260-8677
Kobe University Hospital
Kobe, Hyōgo, 6500017
National Hospital Organization Okayama Medical Center
Okayama, Okayama-ken, 701-1192
Kitasato University Hospital
Sagamihara, Kanagawa, 252-0375
Hokkaido University Hospital
Sapporo, 0608648
Kurume University Medical Center
Sendai, 980-8574
National Cerebral and Cardiovascular Center
Suita, 5658565
Nippon Medical School Hospital
Tokyo, Bunkyo-ku, 113-8603
Kyorin University Hospital
Tokyo, Mitaka-shi, 181-8611

Other trials in Japan

Argentina6 sites

Centro Médico Dra de Salvo
Buenos Aires, Ciudad Autónoma de BuenosAires, C1426ABP
Instituto de Investigaciones Clínicas Mar Del Plata
Buenos Aires, Mar Del Plata, B7600FZN
Hospital Privado Centro Médico de Córdoba
Córdoba, X5016KEH
Instituto de Cardiologia de Corrientes Juana Francisca Cabral
Corrientes, W3400AMZ
Instituto Cardiovascular de Rosario
Rosario, S2000DSR
Hospital Provincial Dr Jose Maria Cullen
Santa Fe, S3000EPV

Other trials in Argentina

Spain5 sites

Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro
Majadahonda
Hospital Universitario Marques de Valdecilla
Santander, Cantabria
Hospital Virgen de La Salud
Toledo, 45004

Other trials in Spain

Australia4 sites

Princess Alexandra Hospital
Brisbane, Queensland, 4102
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
Royal Hobart Hospital
Hobart, Tasmania, 7000
John Hunter Hospital
New Lambton, New South Wales, 2305

Other trials in Australia

Canada4 sites

Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
London Health Sciences Centre
London, Ontario, N6A 5W9
Centre Hospitalier de l'Université Laval
Sainte-Foy, Quebec, G1V 4G5
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Mexico4 sites

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, Mexico City, 14000
Instituto Nacional de Cardiologia Dr. Ignacio Chavez
Mexico City, Mexico City, 14080
Unidad de Investigación Clínica En Medicina SC
Monterrey, Nuevo León, 64718
Hospital Universitario Dr. Jose Eleuterio Gonzalez
Nuevo León, Monterrey, 64460

Other trials in Mexico

Brazil3 sites

Hospital Dia do Pulmão
Blumenau, Santa Catarina, 89010-000
Irmandade Da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-074
Instituto do Coração - HCFMUSP
São Paulo, 05403-900

Other trials in Brazil

Germany3 sites

Universitatsklinkum Carl Gustav Carus an der Tu
Dresden, 01307
Universitatsklinikum Hamburg Eppendorf
Hamburg, 20246
Thorax Klinik
Heidelberg, 69126

Other trials in Germany

Philippines3 sites

Makati Medical Center
Makati, 1229
Philippine General Hospital (PGH)
Manila
Philippine Heart Center
Quezon City, National Capital Region, 1100

Other trials in Philippines

Belgium2 sites

Hospital Erasme
Brussels, 1070
UZ Leuven
Leuven, Vlaams Brabant, 3000

Other trials in Belgium

Czechia2 sites

Vseobecna fakultni nemocnice v Praze
Prague, 128 00
Institut klinicke a experimentalni mediciny
Prague, 140 00

Other trials in Czechia

Israel2 sites

Hadassah University Hospital Ein Kerem
Jerusalem, 91120
Rabin Medical Center
Petah Tikva, 49100

Other trials in Israel

United Kingdom2 sites

Golden Jubilee National Hospital
Glasgow, G81 4HX
Royal Free Hospital
London, NW3 2QG

Other trials in United Kingdom

Netherlands1 site

Vrije Universiteit Amsterdam
Amsterdam, North Holland, 1007 MB

Other trials in Netherlands

About this study

Official title: An Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension

Read the detailed description

Qualified patients will receive 10 mg of bardoxolone methyl once daily until the drug is available through commercial channels or until patient withdrawal, whichever is sooner. Dose de-escalation (down to 5 mg) is permitted during the study, if indicated clinically.

Conditions: Pulmonary Hypertension
Being tested: Bardoxolone methyl
Keywords: Pulmonary Arterial Hypertension, Pulmonary Hypertension, PH, PAH, Bardoxolone methyl, 6-minute walk distance, CDDO-ME, RTA 402, LARIAT, CATALYST, RANGER
Medical subject headings: Hypertension, Pulmonary, Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bardoxolone methylDrug
Also called RTA 402
Capsules of Bardoxolone methyl

Study groups in NCT03068130
Study group	Role	What they receive
Bardoxolone methyl 10 mg	Experimental	Bardoxolone methyl will be administered orally once daily at 10 mg until it becomes commercially available. Dose de-escalation (down to 5 mg) is permitted during the study, if indicated clinically. Receives: Drug: Bardoxolone methyl

What is being measured

The primary outcome is the main question the study is designed to answer.

Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study
Severity was defined using the following definitions: Mild: Symptoms causing no or minimal interference with usual social and functional activities; Moderate: Symptoms causing greater than minimal interference with usual social and functional activities; Severe: Symptoms causing inability to perform usual social and functional activities.
Measured: From time of first dose until the final visit, up to 172 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Apr 201730 Sep 2020

First posted1 Mar 2017
Study start18 Apr 2017
Primary completion30 Sep 2020
Study completion30 Sep 2020

Why it stopped: The company determined that continued exposure of these high-risk PH patients to clinic or in-person visits during the COVID pandemic presented an unacceptable risk.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 261 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03068130
Sponsor's protocol ID: RTA 402-C-1602
Acronym: RANGER
Status last verified: May 2025
First submitted: 22 Feb 2017
Last updated: 11 Jun 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Publications

Chaturvedi G, Dubey N, Panchbhai P, Singh S, Singh R, Baitha U, Parakh N, Narang R, Yadav HN. Mitochondrial-ER crosstalk: An emerging mechanism in the pathophysiology of pulmonary arterial hypertension. Mitochondrion. 2026 Jan;86:102094. doi: 10.1016/j.mito.2025.102094. Epub 2025 Nov 10.
PubMed 41223909

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

All Pulmonary Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension
ClinicalTrials.gov ID: NCT03068130
Acronym / sponsor ID: RANGER / RTA 402-C-1602
Conditions: Pulmonary Hypertension
Keywords: Pulmonary Arterial Hypertension, Pulmonary Hypertension, PH, PAH, Bardoxolone methyl, 6-minute walk distance, CDDO-ME, RTA 402
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: The company determined that continued exposure of these high-risk PH patients to clinic or in-person visits during the COVID pandemic presented an unacceptable risk.
Enrolment: 261 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: 18 Apr 2017 (actual)
Primary completion: 30 Sep 2020 (actual)
Study completion: 30 Sep 2020 (actual)
First posted: 1 Mar 2017 (actual)
Results: Posted 12 Oct 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Bardoxolone methyl 10 mg	Experimental	Drug: Bardoxolone methylBardoxolone methyl will be administered orally once daily at 10 mg until it becomes commercially available. Dose de-escalation (down to 5 mg) is permitted during the study, if indicated clinically.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Treatment-compliant patients who are participating in qualifying ongoing studies and have completed required End-of-Treatment and/or Follow-up visits in a prior clinical study with bardoxolone methyl

Key exclusion criteria (6 listed)

Participation in other investigational clinical studies involving interventional products being tested or used in a way different from the approved form or when used for an unapproved indication;
Patients who have an ongoing SAE from a clinical study that is assessed by the investigator as related to bardoxolone methyl;
Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) while taking study drug;
Women who are pregnant or breastfeeding;
Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bardoxolone methylAlso: RTA 402Capsules of Bardoxolone methyl	Drug	Bardoxolone methyl 10 mg

Primary outcome

Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study
Time frame: From time of first dose until the final visit, up to 172 weeks
Severity was defined using the following definitions: Mild: Symptoms causing no or minimal interference with usual social and functional activities; Moderate: Symptoms causing greater than minimal interference with usual social and functional activities; Severe: Symptoms causing inability to perform usual social and functional activities.

Results and safety

Results posted to the registry on 12 Oct 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bardoxolone Methyl	261	0

Primary outcome: Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study

Time frame: From time of first dose until the final visit, up to 172 weeks. Count of participants. Unit: Participants

Measure	Bardoxolone Methyl n = 261
Number and percent of participants with at least one adverse event	232
Number and percent of participants with a related adverse event	89
Number and percent of participants with a serious adverse event	106
Number and percent of participants with worst adverse event severity of mild	42
Number and percent of participants with worst adverse event severity of moderate	96
Number and percent of participants with worst adverse event severity of severe	94

Population analysed: Safety population (all patients who received at least 1 dose of bardoxolone methyl)

Adverse events

Time frame: The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bardoxolone Methyl	106 of 261 (40.6%)	198 of 261 (75.9%)	17 of 261

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41223909Chaturvedi G, Dubey N, Panchbhai P, Singh S, Singh R, Baitha U, Parakh N, Narang R, Yadav HN. Mitochondrial-ER crosstalk: An emerging mechanism in the pathophysiology of pulmonary arterial hypertension. Mitochondrion. 2026 Jan;86:102094. doi: 10.1016/j.mito.2025.102094. Epub 2025 Nov 10.
Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Related trials for Pulmonary Hypertension

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

96 sites in 15 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bardoxolone methyl in people with Pulmonary Hypertension, run by Biogen at 96 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 96 sites in United States, Japan, Argentina, Spain, Australia and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study (time frame: From time of first dose until the final visit, up to 172 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03068130, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2025.