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

NCT05128929 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: H01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• Calculated Pulmonary Vascular Resistance (PVR)

  Calculated pulmonary vascular resistance (PVR) measured by right heart catheterization (RHC). A normal PVR ranges between 0.25 and 1.6 wood units (WU). Pre-capillary pulmonary hypertension is characterized by a PVR greater than 3 WU. Greater PVR is indicative of increased disease severity. Either Fick or Thermodilution method can be utilized to measure cardiac output (CO) and calculate PVR. Fick method utilizes estimated oxygen consumption to measure CO and calculate PVR, while the thermodilution method utilizes temperature change to measure CO and calculate PVR. All measurements to calculate PVR were obtained at end-expiration (measuring the pressures at functional residual capacity of the lungs).

  Baseline to end of treatment (Week 24; +/- 7 days)

Secondary Outcomes (7)

• 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

  Baseline to end of treatment (Week 24; +/- 7 days)

• Mean Pulmonary Arterial Pressure (mPAP)

  Baseline and end of treatment (Week 24; +/- 7 days)

• 6 Minute Walk Distance Test (6 MWDT)

  Screening (up to 30 days prior to baseline) and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days).

• EMPHASIS-10 Scale Score

  Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days)

• St George Respiratory Questionnaire (SGRQ) Scale Score

  Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days)

Other Outcomes (9)

• Inflammatory Markers and PH-specific Biomarkers (ESR, HSCRP)

  Baseline to end of treatment (Week 24)

• Pro-inflammatory Cytokines

  Baseline to end of treatment (Week 24)

• Forced Expiratory Volume in One Second (FEV1)

  Baseline to end of treatment (Week 24)

Study Arms (2)

Experimental Treatment Oral Hymecromone (H01)

EXPERIMENTAL

Treatment will be initiated. Participants will be administered 800 mg of oral H01 two times a day (total dose: 1600 mg/day). Participants will continue to be on treatment for 24 weeks and will be monitored with assessments.

Drug: Hymecromone (H01)

Placebo

PLACEBO COMPARATOR

Participants randomized to placebo will receive oral tablet placebo (inactive ingredients) two times a day. Participants will continue to be on placebo for 24 weeks and will be monitored with assessments.

Drug: Placebo

Interventions

Hymecromone (H01) DRUG

800 mg oral H01 two times a day (total dose: 1600 mg/day).

Also known as: Cantabiline, Isochol

Experimental Treatment Oral Hymecromone (H01)

Placebo DRUG

Oral tablet placebo (inactive ingredients) two times a day.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Baseline 6MWT: greater than 100 meters and less than 550 meters
• 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.
• 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
• 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.
• 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
• Be able to provide written informed consent and comply with study requirements
• Be able to read, speak and understand English

You may not qualify if:

• 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\*
• Total Lung Capacity (TLC) less than 60% predicted
• FEV1/FVC less than 50% predicted or FEV1 less than 55% predicted
• Inability to safely attempt completion of the 6MWD test
• Use of experimental PAH treatments within the past 3 months
• Current systemic treatment with hymecromone
• 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
• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (2)

• Czepiel K, Nagy N, Panjalingam T, Kalinowski A, Frymoyer AR, Karmouty-Quintana H, Gu B, Hedlin H, Kaber G, Dobrota Lai S, Rosser JI, Bollyky PL, de Jesus Perez V, Zamanian RT. Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension. Thorax. 2025 Aug 15;80(9):632-640. doi: 10.1136/thorax-2024-222725.

  PMID: 40451287 DERIVED

• Salman L, Martinez L, Faddoul G, Manning C, Ali K, Salman M, Vazquez-Padron R. Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next? Kidney360. 2023 Jun 1;4(6):e851-e860. doi: 10.34067/KID.0000000000000126. Epub 2023 Apr 14.

  PMID: 37055910 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

Hymecromone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Umbelliferones; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Roham Zamanian, MD
• Organization: Stanford University School of Medicine

zamanian@stanford.edu

650-725-5495

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 11, 2021
• First Posted: November 22, 2021
• Study Start: April 1, 2022
• Primary Completion: September 21, 2023
• Study Completion: September 29, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-10

Locations

US (1)