Phase 2 Study of REGN13335 Efficacy and Safety in Adults with Pulmonary Arterial Hypertension

The primary objective of this study is to evaluate the effect of REGN13335 on pulmonary vascular resistance in adults with pulmonary arterial hypertension. 5

The secondary objectives include:

• Assessment of safety and tolerability. 4
• Evaluation of N-terminal pro-B-type natriuretic peptide as a biomarker of right ventricular dysfunction. 7
• Evaluation of hemodynamics. 7
• Assessment of exercise capacity. 5
• Description of pharmacokinetics regarding drug concentration following administration. 6
• Evaluation of the effect on soluble target concentrations. 7

This study involves 52 participants diagnosed with pulmonary arterial hypertension. The study population consists of both male and female patients. Participants fall within the age ranges corresponding to codes 3 and 4. Eligible individuals must have a documented clinical diagnosis of Group 1 pulmonary hypertension according to the 7th World Symposium on Pulmonary Hypertension. Inclusion requires a WHO functional class of II or III and a stable regimen of standard of care therapy. Clinical assessments must demonstrate a pulmonary vascular resistance of ≥400 dynes∙sec/cm^5 via right heart catheterization. Additionally, a six-minute walk distance between 150 and 550 meters must be achieved during the screening period.

This Phase 2, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamic effects of REGN13335, a human IgG4 kappa monoclonal antibody targeting platelet-derived growth factor subunit B, in adults diagnosed with pulmonary arterial hypertension. The primary objective is to assess the change from baseline in pulmonary vascular resistance. Secondary endpoints include the assessment of treatment-emergent adverse events, changes in N-terminal pro-B-type natriuretic peptide concentrations, mean pulmonary artery pressure, cardiac output, cardiac index, right atrial pressure, and 6-minute walk distance, as well as plasma concentrations of REGN13335 and total soluble PDGF-B ligands. The study methodology involves a screening period to confirm clinical diagnosis, WHO functional class II or III, stable standard of care therapy, and specific hemodynamic and functional parameters via right heart catheterization. Participation involves scheduled visits to monitor clinical responses and safety through the end-of-study period.

REGN13335 is an experimental human IgG4 kappa monoclonal antibody targeting platelet-derived growth factor subunit B. The investigational product is provided as a powder for solution for either infusion or injection. Administration may be conducted via intravenous, subcutaneous, or intramuscular routes.

A placebo is utilized as a comparator treatment for those not receiving the experimental medication.

The primary efficacy endpoint is the change from baseline in pulmonary vascular resistance (PVR). Secondary endpoints include the change from baseline in mean pulmonary artery pressure, cardiac output, cardiac index, and right atrial pressure. Additionally, the change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and 6-minute walk distance (6MWD) will be evaluated.

Assessment of efficacy also involves measuring the following parameters:

• Plasma concentrations of functional REGN13335.
• Plasma concentrations of total soluble platelet-derived growth factor-B (PDGF-B) ligands.