Trial Outcomes & Findings for Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study). (NCT NCT05128929)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

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

Results posted on

2024-11-26

Participant Flow

17 participants signed the informed consent. Out of these 17 participants,16 were randomized and started the study. The planned open-label extension study did not occur.

Participant milestones

Participant milestones
Measure	Experimental Treatment Oral Hymecromone (H01) Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo Participants receive oral tablet placebo (inactive ingredients) two times a day.
Overall Study STARTED	10	6
Overall Study Primary Analysis (Week 24)	10	6
Overall Study COMPLETED	10	5
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental Treatment Oral Hymecromone (H01) Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo Participants receive oral tablet placebo (inactive ingredients) two times a day.
Overall Study Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.	Total n=16 Participants Total of all reporting groups
Age, Continuous	54.2 years STANDARD_DEVIATION 12.4 • n=5 Participants	66.5 years STANDARD_DEVIATION 3.73 • n=7 Participants	58.8 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

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

Population: Participants with data at the respective time point

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).

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
Calculated Pulmonary Vascular Resistance (PVR) Baseline - TD method	7.97 Wood units (WU) Standard Deviation 2.65	8.23 Wood units (WU) Standard Deviation 4.16
Calculated Pulmonary Vascular Resistance (PVR) Week 24 - TD method	7.27 Wood units (WU) Standard Deviation 2.83	7.11 Wood units (WU) Standard Deviation 2.69
Calculated Pulmonary Vascular Resistance (PVR) Baseline - Fick method	9.04 Wood units (WU) Standard Deviation 3.52	9.97 Wood units (WU) Standard Deviation 5.84
Calculated Pulmonary Vascular Resistance (PVR) Week 24 - Fick method	9.14 Wood units (WU) Standard Deviation 3.39	8.03 Wood units (WU) Standard Deviation 1.10

SECONDARY outcome

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

* 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.

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
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 Grade 1 (mild)	3 Participants	1 Participants
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 Grade 2 (moderate)	1 Participants	3 Participants
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 Grade 3 (severe)	0 Participants	2 Participants
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 Grade 4 (life-threatening)	0 Participants	0 Participants
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 Grade 5 (death)	0 Participants	0 Participants

SECONDARY outcome

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

Population: Participants with data at the respective time point.

Mean pulmonary arterial pressure (mPAP) measured by RHC. A normal mPAP ranges between 9 and 19 mmHg at rest. Pre-capillary pulmonary hypertension is characterized by a mPAP greater than 20 mmHg at rest. Greater mPAP is indicative of increased disease severity. All measurements were obtained at end-expiration.

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
Mean Pulmonary Arterial Pressure (mPAP) Baseline	43.6 mmHg Standard Deviation 10.0	47.5 mmHg Standard Deviation 9.40
Mean Pulmonary Arterial Pressure (mPAP) Week 24	40.2 mmHg Standard Deviation 10.9	42.4 mmHg Standard Deviation 9.34

SECONDARY outcome

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

Population: Participants with data at the respective time point.

The 6MWDT (distance walked in 6 minutes) is used to determine functional exercise capacity, assess treatment efficacy, predict prognosis, and establish rehabilitation programs in PAH/PH patients.

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
6 Minute Walk Distance Test (6 MWDT) Screening	409.0 meters Standard Deviation 110.0	355.0 meters Standard Deviation 73.5
6 Minute Walk Distance Test (6 MWDT) Week 4	383.0 meters Standard Deviation 104.0	347.0 meters Standard Deviation 92.1
6 Minute Walk Distance Test (6 MWDT) Week 12	441.0 meters Standard Deviation 91.1	361.0 meters Standard Deviation 127.0
6 Minute Walk Distance Test (6 MWDT) Week 24	429.0 meters Standard Deviation 101.0	340.0 meters Standard Deviation 112.0

SECONDARY outcome

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

Population: Participants with data at the respective timepoint.

Quality of life (QOL) assessed using the EMPHASIS-10 questionnaire. The minimum score for this questionnaire is 0. The maximum score for this questionnaire is 50. Higher scores are indicative of poorer health-related quality of life (HRQoL) due to pulmonary hypertension.

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
EMPHASIS-10 Scale Score Baseline	20.6 score on a scale Standard Deviation 9.9	19.3 score on a scale Standard Deviation 12.0
EMPHASIS-10 Scale Score Week 4	22.1 score on a scale Standard Deviation 9.6	19.8 score on a scale Standard Deviation 12.2
EMPHASIS-10 Scale Score Week 12	19.0 score on a scale Standard Deviation 7.8	15.0 score on a scale Standard Deviation 12.3
EMPHASIS-10 Scale Score Week 24	15.0 score on a scale Standard Deviation 7.6	14.3 score on a scale Standard Deviation 10.5

SECONDARY outcome

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

Population: Participants with data at the respective timepoint.

Quality of life (QOL) assessed using the St George Respiratory Questionnaire (SGRQ). There are a total of 3 components in the questionnaire, including symptoms, activity, and impacts. Each component has a minimum weight of 0, and a maximum weight of 662.5, 1209.1, and 2117.8, respectively. The minimum weight of the total score (combining all 3 components) is 0, and the maximum weight of total score is 3989.4. The total score is calculated by dividing the summed weights from positive items in the questionnaire by the sum of weights for all items in the questionnaire and multiplying this by 100. The minimum total score is 0, the maximum is 100. Lower scores indicate better health status.

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
St George Respiratory Questionnaire (SGRQ) Scale Score Baseline	32.9 score on a scale Standard Deviation 13.3	36.0 score on a scale Standard Deviation 17.4
St George Respiratory Questionnaire (SGRQ) Scale Score Week 4	38.1 score on a scale Standard Deviation 15.4	35.2 score on a scale Standard Deviation 19.2
St George Respiratory Questionnaire (SGRQ) Scale Score Week 12	31.0 score on a scale Standard Deviation 9.42	36.5 score on a scale Standard Deviation 23.9
St George Respiratory Questionnaire (SGRQ) Scale Score Week 24	27.8 score on a scale Standard Deviation 9.88	39.1 score on a scale Standard Deviation 27.1

SECONDARY outcome

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

Two samples were collected at each time point and mean values were calculated. The average of the two mean values is reported. The normal adult circulating level of hyaluronan ranges between 10 and 100 ng/mL.

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
Serum Hyaluronan (HA) Concentration Baseline	181 ng/mL Standard Deviation 70	186 ng/mL Standard Deviation 32.8
Serum Hyaluronan (HA) Concentration Week 24	222 ng/mL Standard Deviation 193	149 ng/mL Standard Deviation 39.6

SECONDARY outcome

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

N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is laboratory test used for assessing disease severity in pulmonary hypertension. The normal ranges for NT-proBNP are as follows: Male (Reflects 95th percentile w/o CHF ): 18-\<44 yr: 36-93 pg/mL 44-\<54 yr: 36-138 pg/mL 54-\<64 yr: 36-177 pg/mL 64-\<74 yr: 36-229 pg/mL 74 yr: 36-852 pg/mL Females (Reflects 95th percentile w/o CHF ): 18-\<44 yr: 36-178 pg/mL 44-\<54 yr: 36-192 pg/mL 54-\<64 yr: 36-226 pg/mL 64-\<74 yr: 36-353 pg/mL \>74 yr: 36-624 pg/mL

Outcome measures

Outcome measures
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 Participants Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 Participants Participants receive oral tablet placebo (inactive ingredients) two times a day.
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Baseline	1070 pg/ml Standard Deviation 1310	666 pg/ml Standard Deviation 283
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Week 4	1160 pg/ml Standard Deviation 1300	900 pg/ml Standard Deviation 402
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Week 12	1310 pg/ml Standard Deviation 1270	633 pg/ml Standard Deviation 714
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Week 24	846 pg/ml Standard Deviation 506	367 pg/ml Standard Deviation 366

Adverse Events

Experimental Treatment Oral Hymecromone (H01)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 participants at risk Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 participants at risk Participants receive oral tablet placebo (inactive ingredients) two times a day.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/10 • 24 weeks	16.7% 1/6 • 24 weeks
Respiratory, thoracic and mediastinal disorders Thromboembolic event	0.00% 0/10 • 24 weeks	16.7% 1/6 • 24 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/10 • 24 weeks	16.7% 1/6 • 24 weeks

Other adverse events

Other adverse events
Measure	Experimental Treatment Oral Hymecromone (H01) n=10 participants at risk Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day).	Placebo n=6 participants at risk Participants receive oral tablet placebo (inactive ingredients) two times a day.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.0% 1/10 • 24 weeks	0.00% 0/6 • 24 weeks
Cardiac disorders Chest pain - cardiac	10.0% 1/10 • 24 weeks	0.00% 0/6 • 24 weeks
Infections and infestations Lung infection	20.0% 2/10 • 24 weeks	0.00% 0/6 • 24 weeks
General disorders Fatigue	0.00% 0/10 • 24 weeks	16.7% 1/6 • 24 weeks
Gastrointestinal disorders Diarrhea	0.00% 0/10 • 24 weeks	16.7% 1/6 • 24 weeks
Investigations Creatinine increased	0.00% 0/10 • 24 weeks	16.7% 1/6 • 24 weeks

Additional Information

Roham Zamanian, MD

Stanford University School of Medicine

Phone: 650-725-5495

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place