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

Sponsor

Complexa, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT03449524

Collaborator

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

Enrollment

Locations

Arms

24.1

Actual Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
PAH	Drug: 75mg CXA-10 Drug: 150mg CXA-10 Other: Placebo	Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

69 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

CXA-10CXA-10

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 1, 2018

Actual Primary Completion Date :

Aug 5, 2020

Actual Study Completion Date :

Aug 5, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	Arizona Pulmonary Specialists	Phoenix	Arizona	United States	85012
3	University of Arizona	Tucson	Arizona	United States	85724
4	University of California San Francisco	San Francisco	California	United States	94143-2202
5	University of Colorado Health	Aurora	Colorado	United States	80045
6	National Jewish Health	Denver	Colorado	United States	80206
7	Washington Hospital (Medstar)	Washington	District of Columbia	United States	20010
8	George Washington Medical Faculty Associates	Washington	District of Columbia	United States	20037
9	University of Florida Health	Gainesville	Florida	United States	32608
10	Mayo Clinic	Jacksonville	Florida	United States	32224
11	University of Miami	Miami	Florida	United States	33136
12	AdventHealth	Orlando	Florida	United States	32803
13	University of Chicago	Chicago	Illinois	United States	60637
14	Loyola University	Maywood	Illinois	United States	60153-3328
15	Indiana University	Indianapolis	Indiana	United States	46202
16	University of Iowa	Iowa City	Iowa	United States	52242
17	University of Kansas	Kansas City	Kansas	United States	66160
18	Tufts Medical Center	Boston	Massachusetts	United States	02111
19	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115-6110
20	University of Minnesotta	Minneapolis	Minnesota	United States	55455
21	Washington University and Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
22	University of New Mexico Health Sciences Center	Albuquerque	New Mexico	United States	87131
23	NYU Langone Medical Center	New York	New York	United States	10279
24	Duke University	Durham	North Carolina	United States	27710
25	Christ Hospital-Lindner Research Center	Cincinnati	Ohio	United States	45219
26	University of Cincinnati	Cincinnati	Ohio	United States	45267
27	Cleveland Clinic	Cleveland	Ohio	United States	44195
28	The Ohio State University	Columbus	Ohio	United States	43210
29	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma	United States	73112
30	Penn State M.S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
31	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
32	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
33	Vanderbuilt University	Nashville	Tennessee	United States	37232
34	UT Southwestern	Dallas	Texas	United States	75390
35	Texas Tech	El Paso	Texas	United States	79905
36	Houston Methodist	Houston	Texas	United States	77030
37	University of Virginia School of Medicine	Charlottesville	Virginia	United States	22908
38	Inova Medical Campus	Falls Church	Virginia	United States	22042
39	Sentara Medical Group	Norfolk	Virginia	United States	23507
40	Froedert Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
41	Golden Jubilee National Hospital	Glasgow		United Kingdom	G81 4DY
42	Royal Free	London		United Kingdom	NW3 2QG
43	Royal Brompton	London		United Kingdom	SW3 6HP
44	Hammersmith Hospital	London		United Kingdom	W12 0HS
45	Freeman Hospital	Newcastle Upon Tyne		United Kingdom	NE7 7DN
46	Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

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