Oral CXA-10 in Pulmonary Arterial Hypertension

NCT04125745 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY19010004P01HL103455
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to evaluate the safety and tolerability of 12-week oral CXA-10 therapy in subjects with pulmonary arterial hypertension, with additional evaluation on the clinical efficacy of oral CXA-10 on changes in hemodynamics, exercise capacity, cardiovascular function and patient reported outcomes.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.0 in 12 Weeks

  Numbers of treatment-related adverse events is assessed by CTCAE v4.0

  Baseline to 12 Weeks

Secondary Outcomes (7)

• Change From Baseline in Pulmonary Vascular Resistance is Measured at Baseline and 12 Weeks by Right Heart Catheterization

  Baseline and 12 Weeks

• Change From Baseline in Mean Pulmonary Artery Pressure is Measured at Baseline and 12 Weeks by Right Heart Catheterization

  Baseline and 12 Weeks

• Change From Baseline in RV Function as Measured by Tricuspid Annular Plane Systolic Excursion (TAPSE) as Assessed by Echocardiograms at 12 Weeks

  at baseline and 12 weeks

• Changes From Baseline in Functional Exercise Capacity by Assessing 6 Minute Walk Distance Test

  at baseline and 12 weeks

• Change From Baseline in Levels of Serum N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at 12 Weeks

  at Baseline and 12 Weeks

Study Arms (1)

CXA-10

EXPERIMENTAL

Oral CXA-10 300 mg once daily for 12 weeks

Drug: CXA-10

Interventions

CXA-10 DRUG

Each subject will receive oral CXA-10 at the dose of 300 mg once daily for 12 weeks

Also known as: 10-nitro-9(E)-octadec-9-enoic acid

CXA-10

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following criteria will be required on ALL subjects:
• Male or female between 18-80 years of age inclusive at Screening
• Weight ≥ 40 kg or 88 lbs
• Have a WHO Classification of Functional Status Class II or III
• Must meet all of the following hemodynamic criteria by means of a right heart catheterization: mPAP of ≥ 25 mmHg, PVR ≥ 3 wood units, PAWP of ≤ 15 mmHg. A clinical RHC done within 2 months is acceptable to determine eligibility
• Meet all of the following pulmonary function test parameters, completed no more than 12 months before Screening or at screening: forced expiratory volume in one second (FEV1) \> 60% of predicted normal and forced vital capacity (FVC) ≥ 60%
• A 6 MWD test of ≥ 100 m and ≤ 600 m at Screening
• Participants enrolled in an exercise program for pulmonary rehabilitation must be in a stable program 1 month prior to Screening and must agree to maintain their current level of rehabilitation throughout the study. If subjects are not enrolled in an exercise training program for pulmonary rehabilitation they cannot enroll during the Screening/Baseline Period or throughout the study
• If receiving 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) subjects must not have changed their dose \< 4 weeks prior to Screening
• If receiving simvastatin-containing products: simvastatin (Zocor), Vytorin, or any other combination therapy containing simvastatin, the subject's simvastatin dose should not exceed 20 mg/day Note: Subjects using a simvastatin product at dose \> 20 mg/day may be rescreened if their dose has been adjusted to ≤ 20 mg/day, at least 4 weeks prior to Screening with no dose or regimen changes within 4 weeks prior to Baseline
• Subjects must be receiving one or more of the following previously approved PAH therapies: phosphodiesterase type 5 inhibitors (PDE5), endothelin receptor antagonist (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor agonists and must be on stable doses ≥ 3 months) with no dose adjustment within 1 month of Screening
• Ability to provide written informed consent

You may not qualify if:

• Portopulmonary hypertension and pulmonary veno-occlusive diseases
• Congenital heart defects (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired \< 1 year prior to Screening (Group 1 classification of Pulmonary Hypertension)
• Systolic blood pressure \> 160 or \< 90 mmHg or diastolic blood pressure \> 110 mmHg at Screening
• An average QTcF on supine triplicate ECGs at Screening (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 Screening
• Recent cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days prior to Screening
• Recent hospitalization for left heart failure within the last 90 days prior to Screening
• Clinically significant aortic or mitral valve disease defined as greater than moderate regurgitation or moderate 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
• Evidence of a life-threatening cardiac arrhythmias on ECG at Screening as determined by the physician investigator
• Personal or family history of congenital prolonged QTc syndrome or sudden unexpected death due to a cardiac reason
• Receiving intravenous inotropes (e.g. dopamine, dobutamine) 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
• The subject has a history of herbal or natural medication use (including fish oil) within 2 weeks or 5 half-lives, whichever is longer, prior to Baseline
• Subject has taken prednisone at doses \> 15 mg/day; if immunosuppressive medications are used the dose must be stable within 12 weeks prior to Screening and throughout the study
• The subject is currently taking a drug that may affect the assay measurement of serum creatinine (e.g. cimetidine, Bactrim, Pyridium)
• 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 Note: Stable doses of these drugs are permitted (i.e., subject has received the same dose and regimen for at least 30 days prior to Screening with no anticipated changes to the dose or regimen during the course of the study)

Sponsors & Collaborators

• Gladwin, Mark, MD: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Complexa, Inc.: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

CXA-10

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The clinical trial was terminated early due to lack of efficacy based on the negative study outcome from the drug company's multicenter clinical trial. Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Marc Simon, MD, Director of Pulmonary Vascular Disease and Pulmonary Hypertension Comprehensive Care
• Organization: University of California San Francisco

Marc.Simon@ucsf.edu

415-476-1325

Study Officials

• Marc Simon, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: One-arm, open-label

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: October 14, 2019
• Study Start: October 31, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 12, 2022
• Results First Posted: January 12, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Starting 6 months after publication
• Access Criteria: Through a data sharing agreement

Locations

US (1)