Endothelial Cell Activation and Total Pulmonary Resistance in PAH

NCT06035861 | Not Yet Recruiting

• 1 other identifier: 22HH7807
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine whether changes in endothelial cell dysfunction are associated with changes in total pulmonary resistance in patients with pulmonary arterial hypertension

Conditions

Pulmonary Artery Hypertension

Outcome Measures

Primary Outcomes (2)

• Percentage change in plasma sVCAM1, e-selectin, GDF-15 and NT-proBNP

  Percentage change in plasma markers

  6 weeks

• Percentage change in total pulmonary resistance

  Percentage change in total pulmonary resistance

  6 weeks

Study Arms (1)

XBD173

EXPERIMENTAL

6 weeks exposure to XBD173

Drug: XBD173

Interventions

XBD173 DRUG

Participants will be treated with XBD173 90mg twice daily for 6 weeks

Also known as: AC5216

XBD173

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged between 18-75 years old
• PAH which is: idiopathic; PAH heritable; PAH associated with connective tissue disease; PAH after ≥ 1 year repair of congenital systemic to pulmonary shunt; or PAH associated with anorexignes or other drugs.
• Resting mean pulmonary artery pressure ≥25 mmHg, pulmonary capillary wedge pressure ≤15 mmHg, PVR \>5 wood units, and normal or reduced cardiac output, as measured by a previous right heart catheterisation (RHC).
• Have an insertable FDA/CE cardiac rhythm monitor and pulmonary artery pressure monitor that captures cardiopulmonary haemodynamics and daily activity.
• Six-minute walking distance \>50m at entry
• Stable on an unchanged PAH therapeutic regime comprising at least 2 therapies licensed for PAH (any combination of endothelin receptor antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for at least 1 month prior to screening
• Subjects willing to be genotyped for genes that influence XBD173 activity
• Able to provide written informed consent prior to any study mandated procedures
• Contraception: Fertile females (women of childbearing potential) are eligible to participate after a negative highly sensitive pregnancy test, if they are taking a highly effective method of contraception other than the oral contraceptive pill during treatment and until the end of relevant systemic exposure

You may not qualify if:

• Unable to provide informed consent and/or are non-fluent speakers of the English language
• Hypersensitivity to XBD173 or to any of the excipients
• Clinically-significant renal disease (confirmed by creatinine clearance \<30 ml/min per 1.73m2)
• Clinically-significant liver disease (confirmed by serum transaminases \>2 times than upper normal limit)
• Anaemia confirmed by haemoglobin concentration \<10 g/dl
• Individuals known to have haemoglobinopathy sickle cell disease, thalassaemia
• Hospital admission related to PAH or change in PAH therapy within 3 months prior to screening
• History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
• Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis, mild mitral stenosis, moderate mitral regurgitation
• Mechanical or bioprosthetic cardiac valve
• Pericardial constriction, effusion with tamponade physiology, or abnormal left atrial size.
• Restrictive or congestive cardiomyopathy
• Left ventricular ejection fraction ≤50% (measured in echocardiogram at screening)
• Symptomatic coronary disease
• Significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation

Sponsors & Collaborators

• Imperial College London: lead

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension

Interventions

N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: September 13, 2023
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share