Clinical Trial of NS-863 in Participants With Pulmonary Arterial Hypertension (PAH)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Finding Trial to Evaluate the Efficacy and Safety of Orally Administered NS-863 in Participants With Pulmonary Arterial Hypertension (PAH)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Finding Trial to Evaluate the Efficacy and Safety of Orally Administered NS-863 in Participants with Pulmonary Arterial Hypertension (PAH)

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: NS-863 Low Dose; Drug: NS-863 High Dose; Drug: NS-863 Placebo

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to provide written informed consent prior to participation in the trial, which includes the ability to comply with the requirements and restrictions listed in the informed consent form (ICF). Participants must be able to read, comprehend, and write at a level sufficient to complete trial-related materials
• Adult male or female participants 18 to 75 years of age at the time the ICF is signed

• Diagnosed with Group 1 PAH and pre-capillary PH defined by RHC during or at any time prior to the Screening Visit in any of the following subtypes:

  1. Idiopathic PAH (IPAH)
  2. Heritable PAH (HPAH)
  3. PAH associated drug and toxins (DPAH)
  4. PAH associated with connective tissue disease (PAH-CTD)
  5. PAH associated with congenital heart disease (PAH-CHD); simple systemic to pulmonary shunt at least 6 months after surgical repair
• Diagnosed as WHO FC II, III, or IV on stable background therapy

• Results of the RHC within 35 days prior to Day 1 and meet all of the following criteria:

  1. Participants receiving treatment with endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogs or prostacyclin receptor agonists, calcium channel blocker, and/or diuretics are eligible only if on a stable dose for at least 90 days prior to RHC at baseline and throughout the Screening Period. For infusion prostacyclin analogs, dose adjustment based on the participant's body weight is allowed per medical practice. Stable diuretic therapy is defined as no addition of a new diuretic and no switching of a preexistent oral diuretic to parenteral administration; however, dose adjustments (up or down) in preexistent oral diuretics are acceptable
  2. Participants receiving treatment with activin-signaling inhibitor are eligible only if on a stable dose for at least 180 days prior to RHC at baseline and throughout the Screening Period. Dose adjustment based on the participant's body weight is allowed per medical practice.
• Valid 6-minute walk distance (6MWD)
• Women of childbearing potential (WOCBP) must have a negative pregnancy test before receiving the trial treatment and must agree to use contraception from the Screening Visit to at least 30 days after the last dose of the trial treatment. Male participants who could potentially cause pregnancy must agree to use contraception from the Screening Visit to at least 90 days after the last dose of the trial treatment to avoid pregnancy in their partners
• Able to complete the scheduled visits and follow the instructions of the investigator

Exclusion Criteria:

• Current diagnosis of the following PAH Group 1 subtypes:

  1. PAH associated with human immunodeficiency virus (HIV) infection
  2. PAH associated with portal hypertension
  3. PAH associated with schistosomiasis
  4. PAH with features of venous/capillary involvement
  5. Eisenmenger syndrome and PAH associated with prevalent systemic to pulmonary shunts in PAH-CHD

• Have ≥3 of the following LV disease/dysfunction risk factors. :

  1. Body mass index (BMI) ≥30 kg/m2 at the Screening Visit
  2. History of essential hypertension
  3. Diabetes mellitus (any type)
  4. Historical evidence of significant coronary artery disease
• Diagnosis of PH Groups 2, 3, 4, or 5 of the classification
• Moderate or severe obstructive lung disease (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <0.6) or restrictive lung disease (total lung capacity [TLC] <70% of predicted value or lung diffusion capacity for carbon monoxide [DLco] <45% except for PAH-systemic sclerosis) during the Screening Period.

• Moderate or severe liver, renal, blood, or psychiatric disease:

  1. Moderate and severe hepatic impairment by the Child-Pugh scoring system (Class B and Class C)
  2. Moderate and severe renal impairment by estimated glomerular filtration rate (eGFR) <60 mL/min/m2
  3. Have mental disorders or other conditions that make it difficult to follow the protocol
• History of clinically significant (per investigator's judgment) drug or alcohol abuse disorder
• History of calculus urinary
• Initiation of pulmonary rehabilitation within 12 weeks prior to baseline
• Have diseases or symptoms that limit evaluation of 6MWT
• Life expectancy is less than 1 year
• Participants who are pregnant, breastfeeding, or planning to become pregnant during the time of trial participation
• Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with trial participation or trial treatment administration
• Have a history of allergies to the excipients in the trial treatment
• Known HIV positive status
• Active hepatitis due to hepatitis B virus or hepatitis C virus
• Use of any protocol prohibited medications
• Receipt of any live vaccine within 4 weeks prior to the first dose of trial treatment or expected need for live vaccination during trial participation, including at least 4 weeks after the last dose of trial treatment
• The investigator has judged the participant as unwilling or unable to comply with the protocol
• Other concurrent disease and/or medical condition that, in the judgment of the investigator, may put the participant at risk or may influence the results of the trial or the participant's ability to complete the entire duration of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NS-863 Low Dose; NS-863 is an orally administered drug	Drug: NS-863 Low Dose; NS-863 is an orally administered drug
Active Comparator: NS-863 High Dose; NS-863 is an orally administered drug	Drug: NS-863 High Dose; NS-863 is an orally administered drug
Placebo Comparator: NS-863 Placebo; An orally administered NS-863 matching placebo	Drug: NS-863 Placebo; An orally administered NS-863 matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary vascular resistance (PVR) at week 24	PVR is a hemodynamic variable of pulmonary circulation measured by right heart catheterization (RHC).	From baseline to week 24
Number of participants who experienced an adverse event (AE) up to approximately 24 weeks.	An AE is any untoward medical occurrence in a study participant administered a study drug, which did not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug. whether or not it was considered related to the study drug.	From baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-minute walk distance (6MWD) at weeks 12 and 24	The 6MWD is the distance walked in 6 minutes as a measure of functional capacity. This will be assessed using the 6-minute walk test (6MWT).	From baseline to weeks 12 and 24
Change in echocardiogram at weeks 12 and 24	An echocardiogram (echo) is a noninvasive, radiation-free ultrasound test that uses sound waves to produce moving images of the heart's structure, valves, and blood flow.	From baseline to weeks 12 and 24
Change in hemodynamic parameters at Week 24	The hemodynamic parameters include mean right atrium pressure, mean pulmonary arterial pressure, systolic pulmonary artery pressure, diastolic pulmonary arterial pressure, cardiac output, pulmonary artery wedge pressure, stroke volume, and mixed venous oxygen saturation. The hemodynamic parameters will be used to calculate PVR, cardiac index, PVR index, total peripheral resistance, stroke volume index, and pulmonary artery compliance.	From baseline to week 24
Change in Borg dyspnea scale at Week 12 and 24	Borg dyspnea scale is a measure used to assess an individual's exertion level during physical activity after the 6MWT	From baseline to weeks 12 and 24
Change in Word Health Organization Functional Classification (WHO FC) at weeks 12 and 24	The WHO FC describes the severity of symptoms and limitations in physical activity according to the following classes: Class I: No symptoms and no limitation in ordinary physical activity.; Class II: Mild symptoms and slight limitation during ordinary activity.; Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity.; Class IV: Severe symptoms experienced at rest, with inability to carry out any physical activity without discomfort	From baseline to weeks 12 and 24
Change in PAH-Symptoms and Impact (SYMPACT®) at weeks 12 and 24	The PAH-SYMPACT® is a self-rating questionnaire that measures the severity of PAH symptoms and their impact on daily life. The questionnaire consists of 16 symptoms and 25 impact items.	From baseline to weeks 12 and 24

Collaborators and Investigators

• Sponsor: NS Pharma, Inc.
• Collaborators: Nippon Shinyaku Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: January 30, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension
• Other Study ID Numbers: NS-863A-P2-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No