Clinical trial NCT04053543: CXA-10 Study in Subjects With Pulmonary Arterial Hypertension
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
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
Hypertension, Pulmonary
Lung Diseases
Cardiovascular Diseases
Lead sponsor: Complexa, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
name: Innovative Analytics
name: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
First posted: 2019-08-12
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: CXA-10
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
3. Has completed the CXA-10-301 study and demonstrated compliance with study medication administration and study requirements.
4. If receiving simvastatin-containing products: simvastatin (Zocor), Vytorin, or any other combination therapy containing simvastatin, simvastatin dose does not exceed 20 mg/day.
5. 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.
6. 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:

1. Severe hypotension defined by systolic blood pressure \<90 mmHg from sitting blood pressure measurement at Baseline.
2. Hypertensive defined by \>160 mmHg systolic or \>110 mmHg diastolic from sitting blood pressure measurement at Baseline.
3. QTcF on supine ECGs at Baseline (Visit 1) of \>500 msec.
4. 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.
5. Recent cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days prior to Baseline.
6. Recent hospitalization for left heart failure within the last 90 days prior to Baseline.
7. 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.
8. Chronic atrial fibrillation and life-threatening cardiac arrhythmias.
9. Personal or family history of congenital prolonged QTc syndrome or sudden unexpected death due to a cardiac reason.
10. Clinically significant anemia in the opinion of the investigator that precludes enrollment into this study, or Hb \<9 gm/dl.
11. Severe hepatic impairment (Child-Pugh class C with or without cirrhosis) at Baseline or active chronic hepatitis.
12. Received intravenous inotropes within 2 weeks prior to Baseline (e.g. dopamine, dobutamine).
13. History of angina pectoris or other condition that was treated with long or short acting nitrates \<12 weeks of Baseline.
14. History of herbal or natural medication use (including fish oil) within 2 weeks or 5 half-lives, whichever is longer, prior to Baseline.
15. Received prednisone at doses \> 15 mg/ day or changes in immunosuppressive medications \<12 weeks prior to Baseline.
16. 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.

21. 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).

22. Currently taking dimethyl fumarate (Tecfidera™).

23. Any of the following laboratories abnormal and unresolved in CXA-10-301:

1. Absolute lymphocyte counts \< 0.5 x 109 cells/L.
2. 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.
3. eGFR \< 30 mL/min/1.73 m2 (estimated by Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] Creatinine/Cystatin C 2012 algorithm) at Baseline.

   24. 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.

   27. 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.

   28. Clinically significant hyperthyroidism or hypothyroidism not adequately treated.

   29. 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).

   30. Known hypersensitivity to CXA-10, the metabolites, or formulation excipients.

   31. 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.

Primary outcomes:
measure: Incidence of AEs
timeFrame: 6 months
measure: Changes in respiration
timeFrame: 6 months
measure: Changes in heart rate
timeFrame: 6 months
measure: Changes in blood pressure
timeFrame: 6 months
Secondary outcomes:
measure: PAH-specific medication changes
timeFrame: 6 months
measure: 6 Minute Walk Distance
timeFrame: 6 months
measure: Who Classification of Functional Status
timeFrame: 6 months
measure: Clinical worsening
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
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: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
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: 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: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
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: