CXA-10 Study in Subjects With Pulmonary Arterial Hypertension

Sponsor

Complexa, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT04053543

Collaborator

Medpace, Inc. (Industry), Innovative Analytics (Other), Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) (Other)

Enrollment

Locations

Arm

12.1

Actual Duration (Months)

0.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2, multicenter, open-label extension (OLE) of study CXA-10-301, to evaluate the long term safety and efficacy of daily dosing of CXA-10.

Condition or Disease	Intervention/Treatment	Phase
PAH	Drug: CXA-10	Phase 2

Detailed Description

This is a Phase 2, multicenter, open-label extension (OLE) of study CXA-10-301, to evaluate the long term safety and efficacy of daily dosing of CXA-10.

The study will be performed in approximately 50 study centers across the United States and the United Kingdom, which participated in CXA-10-301. Approximately 96 subjects who completed treatment in CXA-10-301 will be eligible to participate in this OLE study, after completing all Visit 9 (Day 1 and Day 2) assessments in CXA-10-301.

Study participation for each subject will last up to approximately 6.5 months. The study will consist of a 6 month open-label treatment period and require 5 clinic visits and 1 telephone visit, including the Baseline Visit completed simultaneously with Visit 9 CXA-10-301, plus a follow-up visit approximately 2 weeks following the last dose of CXA-10.

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

CXA-10CXA-10

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Multi-Center, Open-Label Study to Evaluate Long-term Safety and Efficacy of CXA-10 in Subjects With Pulmonary Arterial Hypertension on Stable Background Therapy: Extension to Study CXA-10-301

Actual Study Start Date :

Aug 9, 2019

Actual Primary Completion Date :

Aug 12, 2020

Actual Study Completion Date :

Aug 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 150mg CXA-10 Once daily dosing of 150mg CXA-10 in the morning	Drug: CXA-10 (10-nitro-9(E)-octadec-9enoic acid)

Arm

Intervention/Treatment

Experimental: 150mg CXA-10

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

Drug: CXA-10

(10-nitro-9(E)-octadec-9enoic acid)

Outcome Measures

Primary Outcome Measures

Incidence of AEs [6 months]
Adverse events occurring during the treatment period
Changes in respiration [6 months]
Change from baseline values at each post-baseline time point
Changes in heart rate [6 months]
Change from baseline values at each post-baseline time point
Changes in blood pressure [6 months]
Change from baseline values at each post-baseline time point

Secondary Outcome Measures

PAH-specific medication changes [6 months]
Addition or removal of PAH-specific medications, including any dose changes
6 Minute Walk Distance [6 months]
Change from baseline in 6-minute walk distance (6MWD)
Who Classification of Functional Status [6 months]
Change from baseline in WHO Classification of Functional Status of Patients with PH
Clinical worsening [6 months]
Death from any cause, hospitalization for worsening PAH, Disease progression, unsatisfactory long-term clinical response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Evidence of a personally signed and dated informed consent document indicating subject has been informed of all pertinent aspects of the study prior to initiation of any study-required procedures.
Is willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Has completed the CXA-10-301 study and demonstrated compliance with study medication administration and study requirements.
If receiving simvastatin-containing products: simvastatin (Zocor), Vytorin, or any other combination therapy containing simvastatin, simvastatin dose does not exceed 20 mg/day.
Currently receiving no more than three of the following previously approved PAH therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonists (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor agonists.
Women of childbearing potential and males with partners of childbearing potential must agree to use a reliable method of contraception while taking study medication.

Exclusion Criteria:

Severe hypotension defined by systolic blood pressure <90 mmHg from sitting blood pressure measurement at Baseline.
Hypertensive defined by >160 mmHg systolic or >110 mmHg diastolic from sitting blood pressure measurement at Baseline.
QTcF on supine ECGs at Baseline (Visit 1) of >500 msec.
Acute myocardial infarction or acute coronary syndrome (ST-Elevation Myocardial Infarction [STEMI], Non STEMI [NSTEMI] and or unstable angina) within the last 90 days prior to Baseline.
Recent cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days prior to Baseline.
Recent hospitalization for left heart failure within the last 90 days prior to Baseline.
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, in the opinion of the investigator.
Chronic atrial fibrillation and life-threatening cardiac arrhythmias.
Personal or family history of congenital prolonged QTc syndrome or sudden unexpected death due to a cardiac reason.
Clinically significant anemia in the opinion of the investigator that precludes enrollment into this study, or Hb <9 gm/dl.
Severe hepatic impairment (Child-Pugh class C with or without cirrhosis) at Baseline or active chronic hepatitis.
Received intravenous inotropes within 2 weeks prior to Baseline (e.g. dopamine, dobutamine).
History of angina pectoris or other condition that was treated with long or short acting nitrates <12 weeks of Baseline.
History of herbal or natural medication use (including fish oil) within 2 weeks or 5 half-lives, whichever is longer, prior to Baseline.
Received prednisone at doses > 15 mg/ day or changes in immunosuppressive medications <12 weeks prior to Baseline.
Currently taking a drug that may affect the assay measurement of serum creatinine (e.g. cimetidine, Bactrim, Pyridium). A list is provided in Appendix H.
Newly prescribed drug or increased dose of an existing drug that is known to prolong the QTc interval and has been associated with Torsades de Pointes (TdP) identified in the CredibleMeds.org website list as known risk (KR) of TdP.

Note: Stable doses of drugs classified as conditional risk (CR) of TdP or possible risk (PR) of TdP are permitted (i.e., subject has received the same dose and regimen for at least 30 days prior to Baseline with no anticipated changes to the dose or regimen during the course of the study).

Currently taking dimethyl fumarate (Tecfidera™).
Any of the following laboratories abnormal and unresolved in CXA-10-301:
Absolute lymphocyte counts < 0.5 x 109 cells/L.
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3.0X upper limit of normal (ULN), alkaline phosphatase (AP) > 2X ULN of liver origin, and total bilirubin >2X ULN. If all liver function tests (LFTs) are within normal limits (WNL) and total bilirubin is elevated, examination of direct and indirect bilirubin may be conducted to evaluate for Rotor's/Gilbert's Syndrome. Subjects with Rotor's/Gilbert's Syndrome may be enrolled.
eGFR < 30 mL/min/1.73 m2 (estimated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] Creatinine/Cystatin C 2012 algorithm) at Baseline.
Females who are pregnant or breastfeeding, or who are trying to conceive. 25. Recent (within 1 year) history of abusing alcohol or illicit drugs. 26. History of any primary malignancy, including a history of melanoma or suspicious undiagnosed skin lesions, or other malignancies (such as thyroid or testicular) that have been curatively treated and with no evidence of disease for at least 3 years or prostate cancer who is not currently or expected, during the study, to undergo radiation therapy, chemotherapy, and/or surgical intervention, or to initiate hormonal treatment.

Exception: subjects with history of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ are eligible for enrollment.

Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, central nervous system or psychiatric disease that, in the opinion of the investigator, may adversely affect the safety of the subject and/or efficacy of the investigational product or severely limit the lifespan of the subject other than the condition being studied.
Clinically significant hyperthyroidism or hypothyroidism not adequately treated.
Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study (e.g., due to expected study medication non- compliance, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures).
Known hypersensitivity to CXA-10, the metabolites, or formulation excipients.
Treatment with any investigational drug (other than CXA-10) or device within 30 days or 5 half-lives (whichever is longer) prior to Baseline (this includes investigational formulations of marketed products, inhaled and topical drugs), or plans to participate in an investigational drug or device study at any time during this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	University of Arizona	Tucson	Arizona	United States	85724
3	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801
4	University of California San Diego	La Jolla	California	United States	92037
5	University of California San Francisco	San Francisco	California	United States	94143-2202
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	University of Chicago	Chicago	Illinois	United States	60637
13	Indiana University	Indianapolis	Indiana	United States	46202
14	University of Kansas	Kansas City	Kansas	United States	66160
15	University of Minnesotta	Minneapolis	Minnesota	United States	55455
16	Washington University and Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
17	NYU Langone Medical Center	New York	New York	United States	10279
18	Duke University	Durham	North Carolina	United States	27710
19	Christ Hospital-Lindner Research Center	Cincinnati	Ohio	United States	45219
20	Cleveland Clinic	Cleveland	Ohio	United States	44195
21	The Ohio State University	Columbus	Ohio	United States	43210
22	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
23	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
24	Vanderbuilt University	Nashville	Tennessee	United States	37232
25	UT Southwestern	Dallas	Texas	United States	75390
26	Texas Tech	El Paso	Texas	United States	79905
27	Houston Methodist	Houston	Texas	United States	77030
28	University of Virginia School of Medicine	Charlottesville	Virginia	United States	22908
29	Inova Medical Campus	Falls Church	Virginia	United States	22042
30	Sentara Medical Group	Norfolk	Virginia	United States	23507
31	Froedert Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
32	Golden Jubilee National Hospital	Glasgow		United Kingdom	G81 4DY
33	Royal Free	London		United Kingdom	NW3 2QG
34	Royal Brompton	London		United Kingdom	SW3 6HP
35	Hammersmith Hospital	London		United Kingdom	W12 0HS
36	Freeman Hospital	Newcastle Upon Tyne		United Kingdom	NE7 7DN
37	Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF