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

PAH Clinical Trial

— PAH  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03449524
• Other study ID #: CXA-10-301
• Status: Terminated
• Phase: Phase 2
• Start date: August 1, 2018
• Est. completion date: August 5, 2020

Study information

• Verified date: August 2020
• Source: Complexa, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 69
• Est. completion date: August 5, 2020
• Est. primary completion date: August 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• PAH

Intervention

Drug:
• 75mg CXA-10
CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)
• 150mg CXA-10
CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United Kingdom	Golden Jubilee National Hospital	Glasgow
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Brompton	London
United Kingdom	Royal Free	London
United Kingdom	Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico
United States	University of Colorado Health	Aurora	Colorado
United States	University of Alabama	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Virginia School of Medicine	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Christ Hospital-Lindner Research Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	UT Southwestern	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Duke University	Durham	North Carolina
United States	Texas Tech	El Paso	Texas
United States	Inova Medical Campus	Falls Church	Virginia
United States	University of Florida Health	Gainesville	Florida
United States	Penn State M.S. Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas	Kansas City	Kansas
United States	Loyola University	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	Froedert Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesotta	Minneapolis	Minnesota
United States	Vanderbuilt University	Nashville	Tennessee
United States	NYU Langone Medical Center	New York	New York
United States	Sentara Medical Group	Norfolk	Virginia
United States	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma
United States	AdventHealth	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Washington University and Barnes Jewish Hospital	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	University of Arizona	Tucson	Arizona
United States	George Washington Medical Faculty Associates	Washington	District of Columbia
United States	Washington Hospital (Medstar)	Washington	District of Columbia

Sponsors (7)

Lead Sponsor	Collaborator
Complexa, Inc.	Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute), Cardiovascular Clinical Science Foundation, Innovative Analytics, Medpace, Inc., MicroConstants, Philips Healthcare

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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