Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

• Register: ClinicalTrials.gov
• Last refreshed on: 12 February 2024
• Main ID: NCT02036970
• Date of registration: 13/01/2014
• Prospective Registration: Yes
• Primary sponsor: Reata, a wholly owned subsidiary of Biogen
• Public title: Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT
• Scientific title: A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension
• Date of first enrolment: May 31, 2014
• Target sample size: 166
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02036970
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Germany, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adult male and female patients = 18 to = 75 years of age upon study consent;

2. BMI > 18.5 kg/m²

3. Symptomatic pulmonary hypertension WHO class II and III;

4. WHO Group I, III, or V PH according to the following criteria:

1. If diagnosed with WHO Group I PAH, then on of the following subtypes:

- Idiopathic or heritable PAH;

- PAH associated with connective tissue disease;

- PAH associated with simple, congenital systemic-to-pulmonary shunts at least
1 year following shunt repair;

- PAH associated with anorexigen or drug-induced toxicity;

- PAH associated with human immunodeficiency virus (HIV); or

2. If WHO Group III PH then primary diagnosis must be one of the following subtypes:

- Connective tissue disease associated ILD (CTD-ILD);

- Idiopathic pulmonary fibrosis (IPF);

- Nonspecific interstitial pneumonia (NSIP); or

3. If WHO Group V PH then patient must be diagnosed with sarcoidosis;

5. Had a diagnostic right heart catheterization performed and documented within 36 months
prior to Day 1 that confirmed a diagnosis of PH

6. If WHO Group I, has been receiving no more than three (3) FDA-approved
disease-specific PAH therapies except for intravenous (iv) prostacyclin/prostacyclin
analogues. PAH therapy must be at a stable dose for at least 90 days prior to Day 1;

7. Has adequate kidney function defined as an estimated glomerular filtration rate (eGFR)
= 45 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) 4-variable
formula;

Exclusion Criteria:

1. Participation in other interventional clinical studies involving pharmaceutical
products being tested or used in a way different from the approved form or when used
for an unapproved indication within 30 days prior to Day 1;

2. Initiation of an exercise program for cardio-pulmonary rehabilitation within 3 months
(90 days) prior to Day 1 or planned initiation during Part 1 of the study;

3. Stopped receiving any PH chronic therapy within 60 days prior to Day 1;

4. Requirement for receipt of intravenous inotropes within 30 days prior to Day 1;

5. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure
(BP) > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during Screening
after a period of rest;

6. Has systolic BP < 90 mm Hg during Screening after a period of rest;

7. WHO Group III or V patients who at rest require supplemental oxygen at a rate of >4
L/min and have peripheral capillary oxygen saturation levels <92%;

8. Has a history of clinically significant left-sided heart disease and/or clinically
significant cardiac disease,including but not limited to any of the following:

1. Congenital or acquired valvular disease if clinically significant apart from
tricuspid valvular insufficiency due to pulmonary hypertension;

2. Pericardial constriction;

3. Restrictive or congestive cardiomyopathy;

4. Left ventricular ejection fraction < 40% per echocardiogram (ECHO) within 60 days
of Day 1;

5. Any current or prior history of symptomatic coronary disease (prior myocardial
infarction, percutaneous coronary intervention, coronary artery bypass graft
surgery, or anginal chest pain);

9. Acutely decompensated heart failure within 30 days prior to Day 1, as per Investigator
assessment;

10. History of atrial septostomy within 180 days prior to Day 1;

11. History of obstructive sleep apnea that is untreated;

12. Has a history of portal hypertension or chronic liver disease, including hepatitis B
and/or hepatitis C (with evidence of recent infection and/or active virus replication)
defined as mild to severe hepatic impairment (Child-Pugh Class A-C);

13. Serum aminotransferase (ALT or AST) levels > the upper limit of normal (ULN) at
Screening;

14. For patients with HIV-associated PAH, any of the following:

1. Concomitant active opportunistic infections within 180 days prior to Screening;

2. Detectable viral load within 90 days prior to Screening;

3. Cluster designation (CD+) T-cell count < 200 mm3 within 90 days prior to
Screening;

4. Changes in antiretroviral regimen within 90 days prior to Screening;

5. Using inhaled pentamidine



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Desquamative Interstitial Pneumonia

Idiopathic Lymphoid Interstitial Pneumonia

Pulmonary Arterial Hypertension

Sarcoidosis

Idiopathic Pleuroparenchymal Fibroelastosis

Interstitial Lung Disease

Respiratory Bronchiolitis Associated Interstitial Lung Disease

Acute Interstitial Pneumonitis

Cryptogenic Organizing Pneumonia

Idiopathic Interstitial Pneumonia

Idiopathic Pulmonary Fibrosis

Pulmonary Hypertension

Intervention(s)

Drug: Bardoxolone methyl

Drug: Placebo

Primary Outcome(s)

Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo [Time Frame: Baseline through Week 16]

Secondary ID(s)

RTA 402-C-1302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 23/07/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02036970