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

Phase 2 Multicenter, Double-Blind, Placebo Controlled, Efficacy, Safety, and Pharmacokinetic Study of 2 Doses of CXA-10 on Stable Background Therapy in Subjects With Pulmonary Arterial Hypertension

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.

Study Overview

• Status: Terminated
• Conditions: PAH
• Intervention / Treatment: Other: Placebo; Drug: 75mg CXA-10; Drug: 150mg CXA-10

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G81 4DY
    • Golden Jubilee National Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free
  • London, United Kingdom, SW3 6HP
    • Royal Brompton
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • San Francisco, California, United States, 94143-2202
      • University of California San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital (Medstar)
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Health
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32803
      • AdventHealth
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Maywood, Illinois, United States, 60153-3328
      • Loyola University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02115-6110
      • Brigham and Women's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesotta
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University and Barnes Jewish Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Sciences Center
  • New York
    • New York, New York, United States, 10279
      • NYU Langone Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital-Lindner Research Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State M.S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbuilt University
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • El Paso, Texas, United States, 79905
      • Texas Tech
    • Houston, Texas, United States, 77030
      • Houston Methodist
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia School of Medicine
    • Falls Church, Virginia, United States, 22042
      • Inova Medical Campus
    • Norfolk, Virginia, United States, 23507
      • Sentara Medical Group
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedert Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 75mg CXA-10; Once daily dosing of 75mg CXA-10 in the morning	Drug: 75mg CXA-10; CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)
Active Comparator: 150mg CXA-10; Once daily dosing of 150mg CXA-10 in the morning	Drug: 150mg CXA-10; CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)
Placebo Comparator: Placebo; Once daily dosing in the morning	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute Walk Distance (6MWD)	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)	6 months

Collaborators and Investigators

• Sponsor: Complexa, Inc.
• Collaborators: Philips Healthcare; Medpace, Inc.; Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute); Cardiovascular Clinical Science Foundation; MicroConstants; Innovative Analytics
• Investigators: Study Director: Theo Danoff, MD, Complexa, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): August 5, 2020
• Study Completion (Actual): August 5, 2020

Study Registration Dates

• First Submitted: February 14, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 28, 2018

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Vascular Diseases; Cardiovascular Diseases; Hypertension; Pulmonary Hypertension; Connective Tissue Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Cardiac MRI; PAH; 6 Minute Walk Test; Hypertension, Pulmonary; Connective Tissue Disease-Associated; 6 Minute Walk Distance; Pulmonary Vascular Resistance; Right Ventricular Function; Familial Primary Pulmonary Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Anti-Inflammatory Agents; CXA-10
• Other Study ID Numbers: CXA-10-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No