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PRIMEx - A Study of 2 Doses of Oral CXA-10 in Pulmonary Arterial Hypertension (PAH)

Phase 2
Terminated
Conditions
PAH
Interventions
Registration Number
NCT03449524
Lead Sponsor
Complexa, Inc.
Brief Summary

This is a multicenter double-blind, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of 2 doses of CXA-10 on stable background therapy in 96 subjects 18 to 80 years of age with PAH.

Detailed Description

This is a multicenter double-blind, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of 2 doses of CXA-10 on stable background therapy in 96 subjects 18 to 80 years of age with PAH.

The study will be performed in approximately 50 study centers across the United States of America and Europe. The recruitment period is anticipated to be approximately 24 months. Approximately 115 subjects will be enrolled to ensure at least 96 subjects complete the study.

Study participation for each subject will last approximately 8 months. The study will consist of a screening period (within 30 days prior to dosing), 180 days (approximately 6 months) treatment period and approximately 14 days follow-up period after the end of treatment visit.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
69
Inclusion Criteria
  • Males and females between 18 to 80 years of age inclusive at Screening
  • Weight ≥40 kg
  • Must have a diagnosis of WHO Group 1 PH
  • Have a World Health Organization (WHO) Classification of Functional Status Class II or III of patients with PH
  • Must meet hemodynamic criteria by means of a right heart catheterization
  • Meet pulmonary function test parameters
  • A 6 MWD test of ≥125m and ≤550m at the visit
  • Subjects must have a resting arterial oxygen saturation (SaO2) ≥90%, with or without supplemental oxygen, as measured by pulse oximetry at Screening
  • Subjects enrolled in a prescribed exercise program for pulmonary rehabilitation must be in a stable program for 3 months prior to Screening (Visit 1) and must agree to maintain their current level of rehabilitation throughout the study. If subjects are not enrolled in a prescribed exercise training program for pulmonary rehabilitation, they cannot enroll during the Screening/Baseline Period or throughout the study
  • If receiving simvastatin-containing products: dose should not exceed 20 mg/day
  • Subjects must be receiving no more than three of the following previously approved PAH therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonist (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor agonists and must be on stable doses (≥3 months) at Screening (Visit 1)
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Exclusion Criteria
  • Contraindications for CMRI imaging
  • WHO Groups 2, 3, 4 and 5 Pulmonary Hypertension
  • Unrepaired congenital heart defects and significant congenital heart defects (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired less than 1 year prior to Screening (Visit 1) (Group 1 classification of Pulmonary Hypertension)
  • QTcF > 500 msec
  • Acute myocardial infarction or acute coronary syndrome within the last 90 days
  • Cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days
  • Hospitalization for left heart failure within the last 90 days
  • Clinically significant aortic or mitral valve disease defined as greater than mild regurgitation or mild stenosis; pericardial constriction; restrictive or constrictive cardiomyopathy; left ventricular dysfunction (LVEF < 50%); left ventricular outflow obstruction; symptomatic coronary artery disease; autonomic hypotension; or fluid depletion
  • Chronic atrial fibrillation and life-threatening cardiac arrhythmias
  • Personal or family history of congenital prolonged QTc syndrome or sudden or sudden unexpected death due to a cardiac reason
  • Clinically significant anemia
  • Severe hepatic impairment or active chronic hepatitis
  • Receiving intravenous inotropes within 2 weeks prior to Screening
  • History of angina pectoris or other condition that was treated with long or short acting nitrates <12 weeks of Screening
  • Received prednisone doses >15mg/day or changes in immunosuppressive medications < 12 weeks prior to Screening (Visit 1)
  • Recent (within 1 year) history of abusing alcohol or illicit drugs.
  • History of any primary malignancy, with no evidence of disease for at least 5 years
  • Treatment with any investigational drug or device within 30 days or 5 half-lives
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
75mg CXA-1075mg CXA-10Once daily dosing of 75mg CXA-10 in the morning
PlaceboPlaceboOnce daily dosing in the morning
150mg CXA-10150mg CXA-10Once daily dosing of 150mg CXA-10 in the morning
Primary Outcome Measures
NameTimeMethod
Right Ventricular Ejection Fraction (RVEF)6 months

• To determine the efficacy of oral doses of CXA-10 on stable background therapy administered for 6 months in subjects with PAH assessed by right ventricular ejection fraction (RVEF) as measured by Cardiac MRI

Pulmonary Vascular Resistance (PVR)6 months

• To determine the efficacy of oral doses of CXA-10 on stable background therapy administered for 6 months in subjects with PAH assessed by pulmonary vascular resistance (PVR) as measured by right heart catheterization (RHC)

Secondary Outcome Measures
NameTimeMethod
6 Minute Walk Distance (6MWD)6 months

To determine the efficacy of oral doses of CXA-10 on stable background therapy administered for 6 months in subjects with PAH assessed by 6 minute walk distance (6MWD)

Trial Locations

Locations (46)

University of Arizona

🇺🇸

Tucson, Arizona, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

Washington Hospital (Medstar)

🇺🇸

Washington, District of Columbia, United States

George Washington Medical Faculty Associates

🇺🇸

Washington, District of Columbia, United States

AdventHealth

🇺🇸

Orlando, Florida, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

University of Florida Health

🇺🇸

Gainesville, Florida, United States

Royal Free

🇬🇧

London, United Kingdom

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Royal Brompton

🇬🇧

London, United Kingdom

Golden Jubilee National Hospital

🇬🇧

Glasgow, United Kingdom

Freeman Hospital

🇬🇧

Newcastle Upon Tyne, United Kingdom

Hammersmith Hospital

🇬🇧

London, United Kingdom

Royal Hallamshire Hospital

🇬🇧

Sheffield, United Kingdom

NYU Langone Medical Center

🇺🇸

New York, New York, United States

Loyola University

🇺🇸

Maywood, Illinois, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

University of New Mexico Health Sciences Center

🇺🇸

Albuquerque, New Mexico, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Penn State M.S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

UT Southwestern

🇺🇸

Dallas, Texas, United States

Texas Tech

🇺🇸

El Paso, Texas, United States

Inova Medical Campus

🇺🇸

Falls Church, Virginia, United States

Sentara Medical Group

🇺🇸

Norfolk, Virginia, United States

The Ohio State University

🇺🇸

Columbus, Ohio, United States

University of Kansas

🇺🇸

Kansas City, Kansas, United States

Washington University and Barnes Jewish Hospital

🇺🇸

Saint Louis, Missouri, United States

University of Virginia School of Medicine

🇺🇸

Charlottesville, Virginia, United States

University of Alabama

🇺🇸

Birmingham, Alabama, United States

Arizona Pulmonary Specialists

🇺🇸

Phoenix, Arizona, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

University of Colorado Health

🇺🇸

Aurora, Colorado, United States

National Jewish Health

🇺🇸

Denver, Colorado, United States

University of Miami

🇺🇸

Miami, Florida, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

University of Minnesotta

🇺🇸

Minneapolis, Minnesota, United States

Duke University

🇺🇸

Durham, North Carolina, United States

Christ Hospital-Lindner Research Center

🇺🇸

Cincinnati, Ohio, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

INTEGRIS Baptist Medical Center

🇺🇸

Oklahoma City, Oklahoma, United States

Vanderbuilt University

🇺🇸

Nashville, Tennessee, United States

Houston Methodist

🇺🇸

Houston, Texas, United States

Froedert Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

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