Clinical trial NCT05128929: Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study).
Official title: Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Hypertension
Keywords: Six Minute Walk Distance Test (6 MWDT)
Right Heart Catheterization (RHC)
Pulmonary Vascular Resistance (PVR)
Pulmonary Function Test (PFT)
Mean Pulmonary Arterial Pressure (mPAP)
Pharmacokinetics
Pharmacodynamics
Hyaluronan
Hymecromone
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2021-11-22
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Calculated Pulmonary Vascular Resistance (PVR)
timeFrame: Baseline to end of treatment (Week 24; +/- 7 days)
Secondary outcomes:
measure: Number of Participants With Adverse Events by Severity Using the NIH Common Terminology Criteria for Adverse Events (CTCAE) as a Measure of Safety and Tolerability of H01 in Adults With Pulmonary Hypertension
timeFrame: Baseline to end of treatment (Week 24; +/- 7 days)
measure: Mean Pulmonary Arterial Pressure (mPAP)
timeFrame: Baseline and end of treatment (Week 24; +/- 7 days)
measure: 6 Minute Walk Distance Test (6 MWDT)
timeFrame: Screening (up to 30 days prior to baseline) and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days).
measure: EMPHASIS-10 Scale Score
timeFrame: Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days)
measure: St George Respiratory Questionnaire (SGRQ) Scale Score
timeFrame: Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days)
measure: Serum Hyaluronan (HA) Concentration
timeFrame: Baseline and end of treatment (Week 24; +/- 7 days)
measure: N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days)
Other outcomes:
measure: Inflammatory Markers and PH-specific Biomarkers (ESR, HSCRP)
timeFrame: Baseline to end of treatment (Week 24)
measure: Pro-inflammatory Cytokines
timeFrame: Baseline to end of treatment (Week 24)
measure: Forced Expiratory Volume in One Second (FEV1)
timeFrame: Baseline to end of treatment (Week 24)
measure: Forced Vital Capacity (FVC) From Pulmonary Function Test (PFT)
timeFrame: Baseline to end of treatment (Week 24)
measure: Total Lung Capacity (TLC) From Pulmonary Function Test (PFT)
timeFrame: Baseline to end of treatment (Week 24)
measure: Lung Diffusion Capacity (DLCO) From Pulmonary Function Test (PFT)
timeFrame: Baseline to end of treatment (Week 24)
measure: Exhaled Breath Condensate (EBC) Hyaluronan Concentrations
timeFrame: Baseline to end of treatment (Week 24)
measure: Pharmacokinetics (H01 and Metabolite Serum Concentrations)
timeFrame: Baseline to end of treatment (Week 24)
measure: HA Fragment Size
timeFrame: Baseline to end of treatment (Week 24)
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
References: