Clinical trial NCT03449524: PRIMEx - A Study of 2 Doses of Oral CXA-10 in Pulmonary Arterial Hypertension (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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Complexa, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
name: Philips Healthcare
name: Cardiovascular Clinical Sciences Inc
name: MicroConstants
name: Innovative Analytics
name: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
First posted: 2018-02-28
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: CXA-10
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Right Ventricular Ejection Fraction (RVEF)
timeFrame: 6 months
measure: Pulmonary Vascular Resistance (PVR)
timeFrame: 6 months
Secondary outcomes:
measure: 6 Minute Walk Distance (6MWD)
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Health
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Washington
country: United States
facility: Washington Hospital (Medstar)
state: District of Columbia
city: Washington
country: United States
facility: George Washington Medical Faculty Associates
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesotta
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University and Barnes Jewish Hospital
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Christ Hospital-Lindner Research Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State M.S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbuilt University
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: El Paso
country: United States
facility: Texas Tech
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia School of Medicine
state: Virginia
city: Falls Church
country: United States
facility: Inova Medical Campus
state: Virginia
city: Norfolk
country: United States
facility: Sentara Medical Group
state: Virginia
city: Milwaukee
country: United States
facility: Froedert Medical College of Wisconsin
state: Wisconsin
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: Royal Free
city: London
country: United Kingdom
facility: Royal Brompton
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Complexa, Inc.
name: Theo Danoff, MD
role: STUDY_DIRECTOR
References: