Pulmonary Arterial HypertensionPhase 2PAHNCT04125745

Oral CXA-10 in Pulmonary Arterial Hypertension

A Phase 2 study testing CXA-10 in people with Pulmonary Arterial Hypertension, run by Gladwin, Mark, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: CXA-10
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 31 Oct 2019to 1 Dec 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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%

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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

Who cannot join

Subjects meeting any of the following exclusion criteria at baseline will be excluded from participating in study:
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

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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)
The subject is currently taking dimethyl fumarate (Tecfidera™)
Females with a positive urine pregnancy test at Screening or prior to dosing or who are pregnant or breastfeeding or who are trying to conceive
Recent (within 6 months) history of abusing alcohol or illicit drugs
History of any primary malignancy, including a history of melanoma or suspicious undiagnosed skin lesions, with the exception of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ or other malignancies curatively treated and with no evidence of disease for at least 5 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
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)
The subject has known hypersensitivity to the CXA-10, the metabolites, or formulation excipients
The subject has had treatment with any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to Screening or plans to participate in an investigational drug study at any time during this study
Subjects who fail inclusion/exclusion criteria may be re-screened once.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pittsburgh
Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Phase 2 Open-Label Study of Safety and Efficacy Trial of CXA-10 in Pulmonary Arterial Hypertension

Read the detailed description

This is a single-center, one-arm, open-label proof of concept safety study and a phase 2a proof of efficacy pre- and post-assessment study of oral CXA-10 for the treatment of pulmonary arterial hypertension.

The investigators hypothesize that administration of CXA-10 for 12 weeks will improves exercise capacity, cardiovascular function and health related quality of life in pulmonary arterial hypertension patients with limited toxicity.

Subjects who meet the inclusion criteria and none of the exclusion criteria will be scheduled within 4 weeks of screening to receive oral CXA-10 at the dose of 300 mg once daily followed by 12 weeks of open-label CXA-10 treatment and then a 4-week safety follow-up. Additional follow-up assessments by telephone will occur in between each outpatient clinic visit.

Conditions: Pulmonary Arterial Hypertension
Being tested: CXA-10
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CXA-10Drug
Also called 10-nitro-9(E)-octadec-9-enoic acid
Each subject will receive oral CXA-10 at the dose of 300 mg once daily for 12 weeks

Study groups in NCT04125745
Study group	Role	What they receive
CXA-10	Experimental	Oral CXA-10 300 mg once daily for 12 weeks Receives: Drug: CXA-10

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Pulmonary vascular resistance (PVR) will be measured by right heart catheterization; results reported as changed from baseline in Woods units. PVR is calculated as (mean pulmonary artery pressure - pulmonary artery wedge pressure)/cardiac output, where pressures are in units of mm Hg and cardiac output is in units of L/min. Pulmonary hypertension is defined as PVR > 3 Woods units. A negative change implies a decrease in PVR which would be considered an improvement.
Measured: Baseline and 12 Weeks
Change From Baseline in Mean Pulmonary Artery Pressure is Measured at Baseline and 12 Weeks by Right Heart Catheterization
Pulmonary Artery mean pressure will be measured by right heart catheterization
Measured: 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
Change from baseline in RV function as measured by tricuspid annular plane systolic excursion (TAPSE) as assessed by echocardiograms at 12 weeks
Measured: at baseline and 12 weeks
Changes From Baseline in Functional Exercise Capacity by Assessing 6 Minute Walk Distance Test
Change from baseline in 6 minute walk distance at 12 weeks
Measured: at baseline and 12 weeks
Change From Baseline in Levels of Serum N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at 12 Weeks
Blood samples will be collected for NT-proBNP analysis
Measured: at Baseline and 12 Weeks
Change From Baseline in Functional Status of Patients as Assessed by New York Heart Association Functional Class
The New York Heart Association Classification of Functional Status of Patients with pulmonary hypertension will be used to classify disease severity in PAH. It places patients in one of four categories based on how much they are limited during physical activity.
Measure Description: Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of dyspnea at rest. If any physical activity is undertaken, discomfort increases.
Measured: at Baseline and 12 Weeks
Change From Baseline in Daily Physical Activity as Measured by a Accelerometer
Continuous physical activity monitoring will be conducted using a noninvasive accelerometer. The device must be worn for a minimum of 7 days at home prior to receiving the first dose of the study drug and prior to the end of the study drug treatment at week 12.
Measured: Baseline and 12 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Oct 20191 Dec 2020

First posted14 Oct 2019
Study start31 Oct 2019
Primary completion1 Dec 2020
Study completion1 Dec 2020

Why it stopped: negative study outcome from Complexa's multicenter clinical trial; no safety concerns

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: One-arm, open-label
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04125745
Sponsor's protocol ID: STUDY19010004
Other IDs: P01HL103455
Acronym: PAH
Status last verified: Dec 2021
First submitted: 28 Aug 2018
Last updated: 12 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: The PI will make individual participant data (IPD) available through a data sharing agreement. After publication, data will be deposited in all available suitable public access databases for archival purposes.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2 Open-Label Study of Safety and Efficacy Trial of CXA-10 in Pulmonary Arterial Hypertension
ClinicalTrials.gov ID: NCT04125745
Acronym / sponsor ID: PAH / STUDY19010004
Conditions: Pulmonary Arterial Hypertension
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: negative study outcome from Complexa's multicenter clinical trial; no safety concerns
Enrolment: 1 participants (actual)
Lead sponsor: Gladwin, Mark, MD
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Complexa, Inc.
Study start: 31 Oct 2019 (actual)
Primary completion: 1 Dec 2020 (actual)
Study completion: 1 Dec 2020 (actual)
First posted: 14 Oct 2019 (actual)
Results: Posted 12 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: One-arm, open-label

Arm	Type	Receives
CXA-10	Experimental	Drug: CXA-10Oral CXA-10 300 mg once daily for 12 weeks

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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%

Key exclusion criteria (26 listed)

Subjects meeting any of the following exclusion criteria at baseline will be excluded from participating in study:
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CXA-10Also: 10-nitro-9(E)-octadec-9-enoic acidEach subject will receive oral CXA-10 at the dose of 300 mg once daily for 12 weeks	Drug	CXA-10

Primary outcome

Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.0 in 12 Weeks
Time frame: Baseline to 12 Weeks
Numbers of treatment-related adverse events is assessed by CTCAE v4.0

7 secondary outcomes

Change From Baseline in Pulmonary Vascular Resistance is Measured at Baseline and 12 Weeks by Right Heart Catheterization
Time frame: Baseline and 12 Weeks
Change From Baseline in Mean Pulmonary Artery Pressure is Measured at Baseline and 12 Weeks by Right Heart Catheterization
Time frame: 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
Time frame: at baseline and 12 weeks
Changes From Baseline in Functional Exercise Capacity by Assessing 6 Minute Walk Distance Test
Time frame: at baseline and 12 weeks
Change From Baseline in Levels of Serum N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at 12 Weeks
Time frame: at Baseline and 12 Weeks
Change From Baseline in Functional Status of Patients as Assessed by New York Heart Association Functional Class
Time frame: at Baseline and 12 Weeks
Change From Baseline in Daily Physical Activity as Measured by a Accelerometer
Time frame: Baseline and 12 Weeks

Results and safety

Results posted to the registry on 12 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CXA-10	1	1

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

Time frame: Baseline to 12 Weeks. Number. Unit: Events

Measure	CXA-10 n = 1
Value	2

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CXA-10	0 of 1 (0%)	1 of 1 (100%)	0 of 1

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. The PI will make individual participant data (IPD) available through a data sharing agreement. After publication, data will be deposited in all available suitable public access databases for archival purposes.

Related trials for Pulmonary Arterial Hypertension

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
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Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marc Simon, MD principal investigator

University of Pittsburgh

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CXA-10 in people with Pulmonary Arterial Hypertension, run by Gladwin, Mark, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.0 in 12 Weeks (time frame: Baseline to 12 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04125745.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2022.