Clinical Trials List
Protocol NumberNS863A-P2-01
NCT Number(ClinicalTrials.gov Identfier)NCT07441200
Not yet recruiting
2026-07-01 - 2029-12-31
Phase II
Not yet recruiting1
A phase 2, randomized, double-blind, placebo-controlled, dose-exploration trial was conducted to evaluate the efficacy and safety of oral NS-863 in participants with pulmonary arterial hypertension (PAH).
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Sponsor
Thermo fisher Co., Ltd. Taiwan Branch
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Trial scale
Multi-Regional Multi-Center
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Update
2026/09/15
Investigators and Locations
Co-Principal Investigator
- YEN-HUNG LIN Division of Cardiovascular Diseases
- YAO-WEN KUO Division of Thoracic Medicine
- 侯鈞賀 Division of Ophthalmology
Co-Principal Investigator
- Kang-Ling Wang 臨床試驗科
- 黃偉銘 Division of Cardiovascular Diseases
- 張皓智 Division of Cardiovascular Diseases
- 季聖筑 Division of Ophthalmology
Co-Principal Investigator
Principal Investigator
Co-Principal Investigator
- 吳書豪 Division of Cardiovascular Diseases
Principal Investigator
Wan-Jing Ho
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Pulmonary hypertension
Objectives
Primary Objective:
To investigate the efficacy and safety of NS-863 compared to placebo by analyzing pulmonary vascular resistance (PVR) and the frequency of adverse events (AEs) in participants with pulmonary arterial hypertension (PAH).
Secondary Objective:
To investigate the efficacy and safety of NS-863 compared to placebo by analyzing secondary efficacy and safety endpoints in PAH participants.
Exploratory Objective:
To further investigate the efficacy of NS-863 compared to placebo by analyzing exploratory endpoints, and to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of NS-863 in PAH participants.
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Test Drug
NS-863
Active Ingredient
NS-863
Dosage Form
Tablets
Dosage
58 mg
Endpoints
Primary efficacy endpoints:
• Change in PVR from baseline to week 24
Primary safety endpoints:
• Number of adverse events (AEs), including treatment-induced AEs (TEAEs), serious AEs (SAEs), treatment-related TEAEs, treatment-related SAEs, and AESIs of particular concern (AESIs)
• Change in PVR from baseline to week 24
Primary safety endpoints:
• Number of adverse events (AEs), including treatment-induced AEs (TEAEs), serious AEs (SAEs), treatment-related TEAEs, treatment-related SAEs, and AESIs of particular concern (AESIs)
Inclution Criteria
To be eligible to participate in the trial, participants must meet all of the following criteria: 1. Be able to provide written informed consent before participating in the trial, including compliance with the requirements and limitations set out in the Participant Consent Form (ICF). 1. Participants must possess the reading, comprehension, and writing skills required to complete the trial-related materials.
2. Adult male or female participants aged 18 to 75 years at the time of signing the ICF.
3. Confirmed by right heart catheterization (RHC) at any time during or prior to the screening follow-up visit, with a diagnosis of Class 1 PAH and pre-microvascular PH, belonging to any of the following subtypes:
a. Idiopathic PAH (IPAH)
b. Heritable PAH (HPAH)
c. Drug- and toxin-associated PAH (DPAH)
d. PAH associated with connective tissue disease (PAH-CTD)
e. PAH associated with congenital heart disease (PAH-CHD); at least 6 months after surgical repair of a simple systemic-pulmonary shunt.
4. Diagnosed as WHO Functional Classification (WHO FC) II, III, or IV. And currently receiving stable background therapy
5. RHC results obtained within 35 days prior to Day 1, meeting all of the following criteria:
a. Pulmonary vascular resistance (PVR) > 5 Wood units (WU)
b. Pulmonary artery wedge pressure (PAWP) or left ventricle end-diastolic pressure (LVEDP) <= 15 mm Hg
c. Mean pulmonary artery pressure (mPAP) > 20 mm Hg
Pulmonary hemodynamics measured by RHC must meet the following criteria:
a. Participants receiving endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, water-soluble guanylate cyclase stimulators, prostacyclin analogs or prostacyclin receptor agonists, calcium channel blockers, and/or diuretics, only if at least 90 days prior to the baseline RHC. Eligibility is contingent upon maintaining a stable daily dose throughout the screening period. For infusions of prostacyclin analogues, dose adjustments based on participant weight may be made according to clinical practice. Stable diuretic therapy is defined as no addition of a new diuretic or conversion of an existing oral diuretic to a non-oral administration; however, dose adjustments (increasing or decreasing) of an existing oral diuretic are permissible.
b. If a participant is receiving an activator signaling inhibitor, eligibility is contingent upon maintaining a stable dose for at least 180 days prior to the baseline RHC and throughout the screening period. Dose adjustments based on participant weight are permitted according to medical practice.
6. During the screening period or before the first dose of treatment on Day 1, participants must complete two 6-minute walk distance (6MWD) measurements, each >= 100 and <= 500 meters (with at least a 4-hour interval between the two measurements), and the difference between the two measurements must be <= 15% (using the higher value).
7. Women of childbearing potential (WOCBP) must have a negative pregnancy test before receiving the trial treatment and must agree to use contraception continuously for at least 30 days from the screening follow-up visit to the last dose of trial treatment. Male participants who could impregnate another person must agree to use contraception for at least 90 days from the screening follow-up visit to the last dose of trial treatment to prevent their partner from becoming pregnant.
8. Participants must be able to complete scheduled follow-up visits and follow the instructions of the trial administrator.
2. Adult male or female participants aged 18 to 75 years at the time of signing the ICF.
3. Confirmed by right heart catheterization (RHC) at any time during or prior to the screening follow-up visit, with a diagnosis of Class 1 PAH and pre-microvascular PH, belonging to any of the following subtypes:
a. Idiopathic PAH (IPAH)
b. Heritable PAH (HPAH)
c. Drug- and toxin-associated PAH (DPAH)
d. PAH associated with connective tissue disease (PAH-CTD)
e. PAH associated with congenital heart disease (PAH-CHD); at least 6 months after surgical repair of a simple systemic-pulmonary shunt.
4. Diagnosed as WHO Functional Classification (WHO FC) II, III, or IV. And currently receiving stable background therapy
5. RHC results obtained within 35 days prior to Day 1, meeting all of the following criteria:
a. Pulmonary vascular resistance (PVR) > 5 Wood units (WU)
b. Pulmonary artery wedge pressure (PAWP) or left ventricle end-diastolic pressure (LVEDP) <= 15 mm Hg
c. Mean pulmonary artery pressure (mPAP) > 20 mm Hg
Pulmonary hemodynamics measured by RHC must meet the following criteria:
a. Participants receiving endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, water-soluble guanylate cyclase stimulators, prostacyclin analogs or prostacyclin receptor agonists, calcium channel blockers, and/or diuretics, only if at least 90 days prior to the baseline RHC. Eligibility is contingent upon maintaining a stable daily dose throughout the screening period. For infusions of prostacyclin analogues, dose adjustments based on participant weight may be made according to clinical practice. Stable diuretic therapy is defined as no addition of a new diuretic or conversion of an existing oral diuretic to a non-oral administration; however, dose adjustments (increasing or decreasing) of an existing oral diuretic are permissible.
b. If a participant is receiving an activator signaling inhibitor, eligibility is contingent upon maintaining a stable dose for at least 180 days prior to the baseline RHC and throughout the screening period. Dose adjustments based on participant weight are permitted according to medical practice.
6. During the screening period or before the first dose of treatment on Day 1, participants must complete two 6-minute walk distance (6MWD) measurements, each >= 100 and <= 500 meters (with at least a 4-hour interval between the two measurements), and the difference between the two measurements must be <= 15% (using the higher value).
7. Women of childbearing potential (WOCBP) must have a negative pregnancy test before receiving the trial treatment and must agree to use contraception continuously for at least 30 days from the screening follow-up visit to the last dose of trial treatment. Male participants who could impregnate another person must agree to use contraception for at least 90 days from the screening follow-up visit to the last dose of trial treatment to prevent their partner from becoming pregnant.
8. Participants must be able to complete scheduled follow-up visits and follow the instructions of the trial administrator.
Exclusion Criteria
Participants meeting any of the following criteria at the screening follow-up visit or baseline period are ineligible to participate in this trial:
1. Currently diagnosed with any of the following PAH subtypes:
a. Human immunodeficiency virus (HIV) infection-related PAH
b. Portal hypertension-related PAH
c. Schistosomiasis-related PAH
d. PAH with venous/microvascular invasion features
e. PAH-CHD with Eisenmenger syndrome or significant prevalent systemic-pulmonary shunts associated with PAH
2. Having ≥3 of the following risk factors for left ventricular (LV) disease/dysfunction:
a. Body mass index (BMI) >= 30 at the screening follow-up visit b. History of primary hypertension
c. Diabetes mellitus (any type)
d. Evidence of significant coronary artery disease, defined as:
i. History of myocardial infarction
ii. History of percutaneous coronary intervention
iii. Coronary angiography (>= 1 vessel with >50% stenosis)
iv. Positive pressure test result on angiography
v. Previous coronary artery surgery
vi. Chronic stable or unstable angina
3. Diagnosed with PH category 2, 3, 4, or 5
4. During the screening period, having moderate or severe obstructive pulmonary disease (forced expiratory volume in one second, FEV1/forced vital capacity, FVC <0.6) or restrictive lung disease (total lung capacity, TLC <70% of the predicted value, or lung diffusion capacity for carbon monoxide). [monoxide, DLco] <45%, except for PAH associated with systemic sclerosis. If the trial administrator deems an ineligible pulmonary function test result due to measurement error or special circumstances, the pulmonary function test may be remeasured once, and the participant does not need to be re-screened.
5. Previous treatment with platelet-derived growth factor receptor (PDGFR) inhibitors for pulmonary hypertension symptoms, and tolerance issues or poor efficacy due to mechanism of action.
6. Moderate or severe liver, kidney, blood, or mental illness
a. Moderate to severe liver function impairment (Grade B and Grade C) as assessed by the Child-Pugh scoring system
b. Moderate to severe kidney function impairment with an estimated glomerular filtration rate (eGFR) <60 mL/min/m^2
c. Anemia (heme <8 g/dL) and clinically significant thrombocytopenia
d. Mental illness or other conditions that may affect adherence to the trial protocol
7. Past 6 8. History of clinically significant (as determined by the trial administrator) drug or alcohol abuse within the past month
9. History of urinary tract stones
10. History of acute kidney injury within 12 weeks prior to the start of the screening follow-up
11. Participants who, at the time of the screening follow-up, have hematuria (>5 RBC/hpf) and proteinuria (urine albumin to creatinine ratio [UACR] >150 mg/g or urine protein to creatinine ratio [UPCR] >400 mg/g)
12. Participants who started pulmonary or cardiac rehabilitation within 12 weeks prior to the baseline period
13. Participants with a disease or symptom that affects the 6-minute walk test (6MWT) assessment (e.g., peripheral vascular disease, musculoskeletal disease, and obesity)
14. Participants who, within 30 days prior to the screening follow-up, participated in another clinical trial involving a drug or medical device, or received treatment with an investigational drug (including investigational formulations of marketed drugs), or whose screening follow-up was conducted 5 days prior to the aforementioned investigational drug trial. Within the terminal half-life (whichever is longer):
14. Life expectancy less than 1 year
15. Pregnant, breastfeeding, or planning to become pregnant during trial participation
16. Using dual platelet inhibitor therapy
17. Having a serious acute or chronic medical or laboratory abnormality that may increase the risk of trial participation or trial treatment administration (e.g., history of intracranial hemorrhage, bleeding event within 6 months prior to the baseline period), or an absolute neutrophil count <1 x 10^9/L or platelet count <50 x 10^9/L at screening
18. History of allergy to excipients used in the trial treatment (D-mannitol, corn starch, hydroxypropyl methylcellulose, low-substituted hydroxypropyl cellulose, magnesium stearate)
19. Known HIV positive
20. Active hepatitis caused by hepatitis B virus or hepatitis C virus
21. Using any of the following contraindicated drugs:
a. Within 7 days or 5 days prior to the baseline period Within one half-life (whichever is longer):
o Warfarin/other vitamin K antagonists or direct-acting oral anticoagulants
o Potent cytochrome P450 (CYP) 3A4 or UDP-glucuronyltransferase (UGT) 1A9 inducers
o P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors
b. Within 28 days prior to the baseline period
o Live vaccines
c. Within 90 days prior to the baseline RHC
o PDGFR inhibitors
d. Within 180 days prior to the baseline RHC
o Lung transplant or PAH-related surgery
Exceptions: Topical medications (including inhalers) in the above categories that are not expected to produce systemic effects may be used.
22. Received any live vaccine within 4 weeks prior to the first trial treatment, or is expected to require vaccination during the trial participation period (including at least 4 weeks after the last dose of trial treatment). (Within the week) Receive an active vaccine
23. The trial administrator determines that the participant is unwilling or unable to follow the trial protocol
24. Other concurrent illnesses and/or medical conditions that, in the trial administrator's judgment, may pose a risk to the participant, may affect the trial results, or may affect the participant's ability to complete the entire trial period.
1. Currently diagnosed with any of the following PAH subtypes:
a. Human immunodeficiency virus (HIV) infection-related PAH
b. Portal hypertension-related PAH
c. Schistosomiasis-related PAH
d. PAH with venous/microvascular invasion features
e. PAH-CHD with Eisenmenger syndrome or significant prevalent systemic-pulmonary shunts associated with PAH
2. Having ≥3 of the following risk factors for left ventricular (LV) disease/dysfunction:
a. Body mass index (BMI) >= 30 at the screening follow-up visit b. History of primary hypertension
c. Diabetes mellitus (any type)
d. Evidence of significant coronary artery disease, defined as:
i. History of myocardial infarction
ii. History of percutaneous coronary intervention
iii. Coronary angiography (>= 1 vessel with >50% stenosis)
iv. Positive pressure test result on angiography
v. Previous coronary artery surgery
vi. Chronic stable or unstable angina
3. Diagnosed with PH category 2, 3, 4, or 5
4. During the screening period, having moderate or severe obstructive pulmonary disease (forced expiratory volume in one second, FEV1/forced vital capacity, FVC <0.6) or restrictive lung disease (total lung capacity, TLC <70% of the predicted value, or lung diffusion capacity for carbon monoxide). [monoxide, DLco] <45%, except for PAH associated with systemic sclerosis. If the trial administrator deems an ineligible pulmonary function test result due to measurement error or special circumstances, the pulmonary function test may be remeasured once, and the participant does not need to be re-screened.
5. Previous treatment with platelet-derived growth factor receptor (PDGFR) inhibitors for pulmonary hypertension symptoms, and tolerance issues or poor efficacy due to mechanism of action.
6. Moderate or severe liver, kidney, blood, or mental illness
a. Moderate to severe liver function impairment (Grade B and Grade C) as assessed by the Child-Pugh scoring system
b. Moderate to severe kidney function impairment with an estimated glomerular filtration rate (eGFR) <60 mL/min/m^2
c. Anemia (heme <8 g/dL) and clinically significant thrombocytopenia
d. Mental illness or other conditions that may affect adherence to the trial protocol
7. Past 6 8. History of clinically significant (as determined by the trial administrator) drug or alcohol abuse within the past month
9. History of urinary tract stones
10. History of acute kidney injury within 12 weeks prior to the start of the screening follow-up
11. Participants who, at the time of the screening follow-up, have hematuria (>5 RBC/hpf) and proteinuria (urine albumin to creatinine ratio [UACR] >150 mg/g or urine protein to creatinine ratio [UPCR] >400 mg/g)
12. Participants who started pulmonary or cardiac rehabilitation within 12 weeks prior to the baseline period
13. Participants with a disease or symptom that affects the 6-minute walk test (6MWT) assessment (e.g., peripheral vascular disease, musculoskeletal disease, and obesity)
14. Participants who, within 30 days prior to the screening follow-up, participated in another clinical trial involving a drug or medical device, or received treatment with an investigational drug (including investigational formulations of marketed drugs), or whose screening follow-up was conducted 5 days prior to the aforementioned investigational drug trial. Within the terminal half-life (whichever is longer):
14. Life expectancy less than 1 year
15. Pregnant, breastfeeding, or planning to become pregnant during trial participation
16. Using dual platelet inhibitor therapy
17. Having a serious acute or chronic medical or laboratory abnormality that may increase the risk of trial participation or trial treatment administration (e.g., history of intracranial hemorrhage, bleeding event within 6 months prior to the baseline period), or an absolute neutrophil count <1 x 10^9/L or platelet count <50 x 10^9/L at screening
18. History of allergy to excipients used in the trial treatment (D-mannitol, corn starch, hydroxypropyl methylcellulose, low-substituted hydroxypropyl cellulose, magnesium stearate)
19. Known HIV positive
20. Active hepatitis caused by hepatitis B virus or hepatitis C virus
21. Using any of the following contraindicated drugs:
a. Within 7 days or 5 days prior to the baseline period Within one half-life (whichever is longer):
o Warfarin/other vitamin K antagonists or direct-acting oral anticoagulants
o Potent cytochrome P450 (CYP) 3A4 or UDP-glucuronyltransferase (UGT) 1A9 inducers
o P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors
b. Within 28 days prior to the baseline period
o Live vaccines
c. Within 90 days prior to the baseline RHC
o PDGFR inhibitors
d. Within 180 days prior to the baseline RHC
o Lung transplant or PAH-related surgery
Exceptions: Topical medications (including inhalers) in the above categories that are not expected to produce systemic effects may be used.
22. Received any live vaccine within 4 weeks prior to the first trial treatment, or is expected to require vaccination during the trial participation period (including at least 4 weeks after the last dose of trial treatment). (Within the week) Receive an active vaccine
23. The trial administrator determines that the participant is unwilling or unable to follow the trial protocol
24. Other concurrent illnesses and/or medical conditions that, in the trial administrator's judgment, may pose a risk to the participant, may affect the trial results, or may affect the participant's ability to complete the entire trial period.
The Estimated Number of Participants
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Taiwan
20 participants
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Global
135 participants
