A Clinical Trial of NS-863 in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)

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 Hypertension Associated With Interstitial Lung Disease (PH-ILD)

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 Hypertension Associated with Interstitial Lung Disease (PH-ILD)

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
• Intervention / Treatment: Drug: NS-863 Low Dose; Drug: NS-863 High Dose; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 177
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be included in the trial:

• 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 80 years of age at the time the ICF is signed

• A confirmed diagnosis of the following WHO Group 3 PH based on computed tomography imaging, which demonstrates the following evidence of ILD performed within 6 months prior to starting the Treatment Period:

  1. ILD
  2. CPFE: only allowed for participants with 15% or less emphysema, and the extent of the ILD must be greater than that of the emphysema. Participants may have any form of ILD (including IIP, IPF, and connective tissue disease) or CPFE

• 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, and/or calcium channel blockers 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.
  2. Participants on chronic medication for underlying lung disease (ie, pirfenidone, etc.) are eligible only if on a stable dose for at least 90 days prior to RHC at baseline and throughout the Screening Period
  3. Participants receiving treatment with oxygen therapy are eligible only if beginning for at least 30 days prior to RHC at baseline and throughout the Screening Period, and on a stable dose of oxygen for 30 minutes before RHC
• Valid 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:

Participants meeting any of the following criteria at the Screening Visit or baseline are ineligible to participate in this trial:

• Have a diagnosis of PAH or PH for reasons other than WHO Group 3 PH-ILD as outlined in inclusion criterion 3

• Have evidence of clinically significant left-sided heart disease, as defined by:

  a. LVEF <40% Notes: Participants with abnormal LV function attributable entirely to impaired LV filling due to the effects of RV overload (ie, RV hypertrophy and/or dilatation) will not be excluded

• Receiving > 6 L/min of oxygen supplementation by any mode of delivery at rest at baseline

• 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 within the last 6 months
• Have mental disorders or other conditions that make it difficult to follow the protocol
• History of calculus urinary
• Have a deterioration of underlying disease or a lung or upper respiratory tract infection within 30 days prior to baseline
• Initiation of pulmonary rehabilitation within 12 weeks prior to baseline
• At the time of consent, more than 1 year has passed since registration for lung transplantation, or surgery related to PH treatment is scheduled
• Have diseases or symptoms that limit evaluation of 6MWT (eg, peripheral vascular disease, musculoskeletal disorders, and obesity)
• Participants who have participated in another clinical trial involving a drug or medical device, or have received treatment with an investigational product (including investigational formulations of marketed products), within 30 days prior to the Screening Visit or within 5 terminal phase half-lives of the investigational product, whichever is longer
• Life expectancy is less than 6 months
• Acute pulmonary embolism within 90 days prior to baseline
• Current cigarette or e-cigarette smokers or those who have quit within the past 6 months, with a history of ≥20 pack-years smoking
• Participants who are pregnant, breastfeeding, or planning to become pregnant during the time of trial participation
• Use of dual platelet inhibitor therapy
• 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 human immunodeficiency virus (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: Placebo; An orally administered NS-863 matching placebo	Other: 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 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 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 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 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 The King's Brief Interstitial Lung Disease (KBILD) at weeks 12 and 14.	The KBILD questionnaire measures the impact of interstitial lung disease (ILD) on a participant's daily life and overall well-being and consists of 15 items that participants will self-complete, covering 3 domains: psychological, breathlessness and activities, and chest symptoms.	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): September 14, 2028
• Study Completion (Estimated): December 14, 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

• Other Study ID Numbers: NS-863B-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