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

NCT03449524 | Terminated Phase 2 FDA Drug

• 1 other identifier: CXA-10-301
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 46

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.

Conditions

PAH

Keywords

Pulmonary Arterial Hypertension; Pulmonary Hypertension; PAH; Connective Tissue Disease-Associated; 6 Minute Walk Test; 6 Minute Walk Distance; Pulmonary Vascular Resistance; Cardiac MRI; Right Ventricular Function; Hypertension; Familial Primary Pulmonary Hypertension; Connective Tissue Diseases; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases

Outcome Measures

Primary Outcomes (2)

• Right Ventricular Ejection Fraction (RVEF)

  • 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

  6 months

• Pulmonary Vascular Resistance (PVR)

  • 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)

  6 months

Secondary Outcomes (1)

• 6 Minute Walk Distance (6MWD)

  6 months

Study Arms (3)

75mg CXA-10

ACTIVE COMPARATOR

Once daily dosing of 75mg CXA-10 in the morning

Drug: 75mg CXA-10

150mg CXA-10

ACTIVE COMPARATOR

Once daily dosing of 150mg CXA-10 in the morning

Drug: 150mg CXA-10

Placebo

PLACEBO COMPARATOR

Once daily dosing in the morning

Other: Placebo

Interventions

75mg CXA-10 DRUG

CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)

75mg CXA-10

150mg CXA-10 DRUG

CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)

150mg CXA-10

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Complexa, Inc.: lead
• Medpace, Inc.: collaborator
• Philips Healthcare: collaborator
• Cardiovascular Clinical Sciences Inc: collaborator
• MicroConstants: collaborator
• Innovative Analytics: collaborator
• Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute): collaborator

Study Sites (46)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Arizona Pulmonary Specialists

Phoenix, Arizona, 85012, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of California San Francisco

San Francisco, California, 94143-2202, United States

Location

University of Colorado Health

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Washington Hospital (Medstar)

Washington D.C., District of Columbia, 20010, United States

Location

George Washington Medical Faculty Associates

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

Location

University of Florida Health

Gainesville, Florida, 32608, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

AdventHealth

Orlando, Florida, 32803, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Loyola University

Maywood, Illinois, 60153-3328, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115-6110, United States

Location

University of Minnesotta

Minneapolis, Minnesota, 55455, United States

Location

Washington University and Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

NYU Langone Medical Center

New York, New York, 10279, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Christ Hospital-Lindner Research Center

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

INTEGRIS Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

Penn State M.S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Vanderbuilt University

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

Texas Tech

El Paso, Texas, 79905, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22908, United States

Location

Inova Medical Campus

Falls Church, Virginia, 22042, United States

Location

Sentara Medical Group

Norfolk, Virginia, 23507, United States

Location

Froedert Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

Location

Royal Free

London, NW3 2QG, United Kingdom

Location

Royal Brompton

London, SW3 6HP, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension; Familial Primary Pulmonary Hypertension; Connective Tissue Diseases; Vascular Diseases; Cardiovascular Diseases; Lung Diseases

Interventions

CXA-10

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Skin and Connective Tissue Diseases

Study Officials

• Theo Danoff, MD

  Complexa, Inc.

  STUDY DIRECTOR

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: CXA-10

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 28, 2018
• Study Start: August 1, 2018
• Primary Completion: August 5, 2020
• Study Completion: August 5, 2020
• Last Updated: August 10, 2020

Record last verified: 2020-08

Locations

GB (6); US (40)