Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study).

Pulmonary Hypertension Clinical Trial

— SATURN  

Official title:

Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05128929
• Other study ID #: H01
• Status: Completed
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: September 29, 2023

Study information

• Verified date: October 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a prospective, randomized, double-blind, study of H01 (Hymecromone) in adults with pulmonary hypertension (PH). The primary objective of this study is to evaluate the safety and tolerability of oral H01 and the potential benefit of oral H01 on clinical measures of PH disease severity over 24 weeks.

Study Hypothesis:

Oral H01, at doses of 1600 mg per day, will be a safe and well-tolerated agent in adults with pulmonary hypertension over 24 weeks

Description:

The study's objectives are to evaluate:

• The changes in clinical and functional measures (pulmonary function test, pulmonary vascular resistance, mean pulmonary arterial pressure, and 6 Minute Walk Distance Test) in adults with PH treated with oral H01

• The safety and tolerability of the use of oral H01 for PH over 24 weeks using health criteria/evaluations (Common Terminology Criteria for Adverse Events (CTCAE), quality of life (QOL) score, EMPHASIS-10 score and St George Respiratory Questionnaire (SGRQ) score)

• To investigate the clinical efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) markers (serum HA concentration, inflammatory markers and cytokines, NT-proBNP, and H01 and metabolite serum concentrations) in this population following oral H01 use

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 29, 2023
• Est. primary completion date: September 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Classified as WHO functional class II/III/IV despite treatment with maximally tolerated doses of 2 or more treatment modalities (exp. PDE5 inhibitors, guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids)

2. Baseline 6MWT: greater than 100 meters and less than 550 meters

3. Established diagnosis of Group 3 pulmonary hypertension as a result of interstitial lung disease OR established diagnosis of Group 1 pulmonary hypertension as a result of connective tissue disease, idiopathic, hereditary, drugs, or toxins.

4. Right heart catheterization at randomization showing pre-capillary pulmonary hypertension (mPAP = 25 mmHg and PVR > 400 dynes * sec * cm^ -5) and:

• PCWP =20 mmHg for Group 3 PH patients and Group 1 PAH patients

5. Participants on chronic medication for PAH, PH, or underlying lung disease must be on a stable and optimized dose for at least 90 days prior to the first dose of the study drug.

6. Female participants who are heterosexually active must use an acceptable method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or Hormone-based contraceptive

7. Be able to provide written informed consent and comply with study requirements

8. Be able to read, speak and understand English

Exclusion Criteria:

1. Participants with a diagnosis of PAH or PH for reasons due to any of the following:

• Group 2, 4, or 5

• Group 1 due to HIV, veno-occlusive disease, porto-pulmonary hypertension, congenital heart disease

• Group 3 due to severe chronic obstructive pulmonary disease (COPD) or obstructive sleep apnea (OSA)

• Note: participants with overlapping syndromes will be evaluated on a case-by-case basis by the recruiting physician*

2. Total Lung Capacity (TLC) less than 60% predicted

3. FEV1/FVC less than 50% predicted or FEV1 less than 55% predicted

4. Inability to safely attempt completion of the 6MWD test

5. Use of experimental PAH treatments within the past 3 months

6. Current systemic treatment with hymecromone

7. Left sided heart disease as defined by either a PCWP greater than 20 mmHg and/or left ventricular ejection fraction less than 40%

• Note: participants with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload (ie right ventricular hypertrophy and/or dilatation) are not excluded

8. Participants must not have 3 or more of the following left ventricular disease / dysfunction risk factors:

• Body mass index (BMI) greater than 30kg/m2

• History of essential hypertension requiring medication

• Diabetes mellitus

9. Historical evidence of significant coronary disease established by any of the following:

• History of myocardial infarction

• History of percutaneous coronary intervention or coronary artery bypass graft

• Angiographic evidence of greater than 50% stenosis in at least one coronary artery

• Positive stress test with imaging

• Stable angina

10. Significant valvular heart disease as determined by more than moderate findings on echocardiogram or history of valve replacement

11. Pregnant or actively breastfeeding

12. Female participants with childbearing potential not willing to use a form of birth control (including abstinence) during the study

13. Inability to undergo right heart catheterization

14. Acute pulmonary embolism within 90 days of randomization

15. Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomizations

16. Use of any inhaled tobacco products or significant history of drug abuse within 3 months prior to randomization

17. Subject is receiving greater than 10L/min of oxygen supplementation by any mode of delivery at rest at baseline

18. Body mass index greater than 40kg/m2

19. Participants with history of dysphagia, achalasia, or difficulty swallowing capsules, tablets or pills

20. Participants with liver failure or AST or ALT greater than 2 times the upper limit of normal

21. Participants with total bilirubin levels greater than 2 times the upper limit of normal

22. Participants with CrCl less than 45

23. Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization

24. Known allergy to hymecromone or any component thereof

25. Known allergy to any component of placebo (including wheat allergy, celiac disease, rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption)

26. Physician concern that participant may not adhere to the study protocol

27. Significant psychiatric, addictive, or other disorder that compromises the subject's ability to provide informed consent

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Hypertension

Intervention

Drug:
• Hymecromone (H01)
800 mg oral H01 two times a day (total dose: 1600 mg/day).
• Placebo
Oral tablet placebo (inactive ingredients) two times a day.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Inflammatory markers and PH-specific biomarkers (ESR, HSCRP)	Change in inflammatory markers and PH-specific biomarkers (ESR, HSCRP)	Baseline to end of treatment (Week 24)
Other	Pro-inflammatory cytokines	Change in pro-inflammatory cytokines	Baseline to end of treatment (Week 24)
Other	Forced Expiratory Volume in one second (FEV1)	Change in Forced Expiratory Volume in one second (FEV1)	Baseline to end of treatment (Week 24)
Other	Forced Vital Capacity (FVC) from Pulmonary Function Test (PFT)	Change in Forced Vital Capacity (FVC) from pulmonary function test (PFT)	Baseline to end of treatment (Week 24)
Other	Total Lung Capacity (TLC) from Pulmonary Function Test (PFT)	Change in Total Lung Capacity (TLC) from pulmonary function test (PFT)	Baseline to end of treatment (Week 24)
Other	Lung diffusion capacity (DLCO) from Pulmonary Function Test (PFT)	Change in Lung diffusion capacity (DLCO) from pulmonary function test (PFT)	Baseline to end of treatment (Week 24)
Other	Exhaled breath condensate (EBC) hyaluronan concentrations	Change in exhaled breath condensate (EBC) hyaluronan concentrations	Baseline to end of treatment (Week 24)
Other	Pharmacokinetics (H01 and metabolite serum concentrations)	Describe the pharmacokinetics (H01 and metabolite serum concentrations)	Baseline to end of treatment (Week 24)
Other	HA fragment size	Describe HA fragment size	Baseline to end of treatment (Week 24)
Primary	Change in Pulmonary Vascular Resistance (PVR)	Change in pulmonary vascular resistance (PVR) measured by right heart catheterization (RHC).	Baseline to end of treatment (Week 24)
Secondary	The safety and tolerability of H01 in adults with pulmonary hypertension using the NIH Common Terminology Criteria for Adverse Events (CTCAE)	Grade 1: Mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.; Grade 2: Moderate minimal, local or noninvasive intervention indicated; limiting age- appropriate instrumental activities of daily living (ADL).; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.; Grade 4: Life-threatening consequences; urgent intervention indicated.; Grade 5: Death related to AE.	Baseline to end of treatment (Week 24)
Secondary	Change in Mean Pulmonary Arterial Pressure (mPAP)	Change in mean pulmonary arterial pressure (mPAP) by RHC	Baseline to end of treatment (Week 24)
Secondary	6 Minute Walk Distance Test (6 MWDT)	Change in 6 minute walk distance as measured by 6 MWDT	Baseline to end of treatment (Week 24)
Secondary	Quality of Life (QOL) score, EMPHASIS-10 score and St George Respiratory Questionnaire (SGRQ) score	Change in quality of life (QOL) score, EMPHASIS-19 score and St George Respiratory Questionnaire (SGRQ) score	Baseline to end of treatment (Week 24)
Secondary	Serum HA concentration	Change in serum HA concentration	Baseline to end of treatment (Week 24)
Secondary	N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)	Change in NT-proBNP	Baseline to end of treatment (Week 24)