Trial Outcomes & Findings for A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (NCT NCT03738150)

NCT ID: NCT03738150

Last Updated: 2024-08-27

Results Overview

Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 21 participants
• Primary outcome timeframe: Baseline and 24 weeks
• Results posted on: 2024-08-27

Participant Flow

Participant milestones

Measure	Sotatercept Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Base Study STARTED	21
Base Study COMPLETED	20
Base Study NOT COMPLETED	1
Extension Study STARTED	20
Extension Study COMPLETED	19
Extension Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Sotatercept Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Base Study Withdrawal by Subject	1
Extension Study Withdrawal by Subject	1

Baseline Characteristics

All participants who completed treatment period, had iCPET assessment and cardiac magnetic resonance imaging (MRI) at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at End Of Treatment (EOT), with no major protocol deviations.

Baseline characteristics by cohort

Measure	Sotatercept n=21 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Age, Continuous	45.3 years STANDARD_DEVIATION 15.06 • n=21 Participants
Sex: Female, Male Female	17 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=21 Participants
Race (NIH/OMB) White	17 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=21 Participants
Peak Oxygen Uptake (VO2 max) at Baseline	11.02 mL/min/kg STANDARD_DEVIATION 3.204 • n=17 Participants • All participants who completed treatment period, had iCPET assessment and cardiac magnetic resonance imaging (MRI) at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at End Of Treatment (EOT), with no major protocol deviations.

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at End Of Treatment (EOT), with no major protocol deviations.

Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks	1.28 mL/min/kg Standard Deviation 2.628

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

Each participant's RV SV was measured by cardiac MRI at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Right Ventricular Stroke Volume (RV SV) at 24 Weeks	-27.306 mL Standard Deviation 26.5786

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

Each participant's RV ESV was measured by cardiac MR imaging at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks	-39.151 mL Standard Deviation 22.5544

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

Each participant's RV EDV was measured by cardiac MR imaging at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Right Ventricular End-Diastolic Volume (RV EDV) at 24 Weeks	-66.459 mL Standard Deviation 37.3311

SECONDARY outcome

Timeframe: Baseline and 24 Weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

Each participant's RV EF was measured by cardiac MR imaging at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Percent Change From Baseline in Right Ventricular Ejection Fraction (RV EF) at 24 Weeks	-1.3 Percent change Standard Deviation 8.48

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

Each participant's RV SVI was measured by cardiac MR imaging at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Right Ventricular Stroke Volume Index (RV SVI) at 24 Weeks	-15.073 mL/m^2 Standard Deviation 14.8219

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

Each participant's RV mass was measured by cardiac MR imaging at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Right Ventricular (RV) Mass at 24 Weeks	-6.240 grams Standard Deviation 13.3558

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

VE/VCO2 slope refers to the slope of the regression line of Minute Ventilation (VE) in liters/minute in the Y-axis and corresponding carbon dioxide production per minute (VCO2) in liters/minute in the X-axis plotted with multiple measurements taken during exercise. Each participant's VE/VCO2 slope at peak exercise was measured by an iCPET at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Ventilatory Efficiency (VE/VCO2 Slope) at 24 Weeks	-8.87 Unitless Standard Deviation 12.298

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in Cardiac Index at 24 Weeks.

Each participant's cardiac index at peak exercise was measured by iCPET at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=16 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Cardiac Index at 24 Weeks	0.411 Liter/min/m^2 Standard Deviation 1.1944

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks.

Each participant's pulmonary arterial pressure at peak exercise was measured by iCPET at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=16 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks	-14.9 mmHg Standard Deviation 13.22

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in Ca-vO2 at 24 Weeks.

Each participant's Ca-vO2 at peak exercise was measured by iCPET at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Arteriovenous O2 Content Difference (Ca-vO2) at 24 Weeks	0.63 mL/100 mL Standard Deviation 2.131

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in PVR at 24 Weeks.

Each participant's PVR, at resting supine, was measured by right heart catheterization (RHC) at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks	-305.728 dynes*sec/cm^5 Standard Deviation 313.9827

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in 6MWD at 24 Weeks.

6MWD is measured by an exercise test known as 6MWT that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in basic mobility.

Outcome measures

Measure	Sotatercept n=16 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks	66.35 meters Standard Deviation 85.659

SECONDARY outcome

Timeframe: Baseline and 24 Weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and had data for Change from Baseline in Concentration of NT-proBNP at 24 Weeks.

Each participant's laboratory biomarkers N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) or brain-type natriuretic peptide (BNP) were measured at baseline and at 24 weeks.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks	-623.1 pg/mL Standard Deviation 840.56

SECONDARY outcome

Timeframe: Baseline and 24 Weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.

The World Health Organization (WHO) functional class describes how severe a person's pulmonary hypertension symptoms are. There are four different classes - I is the mildest and IV the most severe form of pulmonary hypertension.

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Change From Baseline in WHO (World Health Organization) Functional Class at 24 Weeks	-0.76 WHO functional class Standard Deviation 0.903

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All participants who received at least one dose of study treatment.

An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Outcome measures

Measure	Sotatercept n=21 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Number of Participants With One or More Adverse Events (AEs)	20 Participants

SECONDARY outcome

Timeframe: Up to 102 weeks

Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Number of Participants Who Experienced One or More Events Indicative of Clinical Worsening of PAH.

Events that indicate clinical worsening of PAH include death, need for and/or worsening-related listing for lung and/or heart transplant, need to initiate an approved PAH SOC rescue therapy, PAH-specific hospitalization, or functional deterioration (worsened WHO Functional Class AND 15% decrease in 6MWD).

Outcome measures

Measure	Sotatercept n=17 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Number of Participants Who Experienced One or More Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH)	1 Participants

SECONDARY outcome

Timeframe: Day 1 of Cycle 9 (Each cycle was 21 days.)

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Observed Ctrough of Sotatercept at Cycle 9, and followed the dosing regimen.

Ctrough is the plasma concentration of a drug prior to administration.

Outcome measures

Measure	Sotatercept n=14 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9	5884.79 ng/mL Standard Deviation 2933.77

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment and had at least 1 blood sample analyzed for PK, had data for Cmax of Sotatercept at Cycle 9, and followed the dosing regimen.

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cmax parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Maximum Plasma Concentration (Cmax) of Sotatercept at Cycle 9	9732.785 ng/mL Standard Deviation 2852.373

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Cmin of Sotatercept at Cycle 9, and followed the dosing regimen.

Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cmin parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Minimum Plasma Concentration (Cmin) of Sotatercept at Cycle 9	6234.303 ng/mL Standard Deviation 2466.046

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Cavg of Sotatercept at Cycle 9, and followed the dosing regimen.

Cavg is calculated by area under the plasma concentration versus dosing interval time curve at steady-state divided by the dosing interval. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cavg parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Average Concentration (Cavg) of Sotatercept at Cycle 9	8221.907 ng/mL Standard Deviation 2749.846

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for AUC0-T of Sotatercept at Cycle 9, and followed the dosing regimen.

AUC0-T (area under the plasma concentration versus time curve from time zero after a dose is given to a period of one 21-day cycle) is a measure of the mean concentration levels of a drug in the plasma at steady state. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The AUC0-T parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Area Under the Concentration-Time Curve From 0 to T (AUC0-T) of Sotatercept at Cycle 9	172659.953 ng*day/mL Standard Deviation 57746.622

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Apparent t1/2 of Sotatercept at Cycle 9, and followed the dosing regimen.

t1/2 is the elimination half-life of study drug: the time it takes for half of the study drug in the blood plasma to dissipate. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The t1/2 parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Apparent Terminal Half-life (t1/2 ) of Sotatercept at Cycle 9	21.919 Days Standard Deviation 5.861

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Apparent Serum CL of Sotatercept at Cycle 9, and followed the dosing regimen.

Apparent serum CL is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The apparent serum CL parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Apparent Serum Clearance (CL) of Sotatercept at Cycle 9	0.213 Liters/day Standard Deviation 0.077

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, and had data for Apparent Vz/F of Sotatercept at Cycle 9, and followed the dosing regimen.

Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Vz/F parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=15 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Apparent Volume of Distribution (Vz/F) of Sotatercept at Cycle 9	3.969 Liters Standard Deviation 1.078

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle: Cycles 1-9

Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Ka of Sotatercept at Cycle 9, and followed the dosing regimen.

Ka is the proportionality constant that relates the rate of drug absorbed into the body. Ka is a value used to describe the rate at which a drug enters into the system. It is expressed in units of time. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Ka parameter is derived from this preliminary popPK modeling.

Outcome measures

Measure	Sotatercept n=14 Participants Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period.
Absorption Rate Constant (Ka) of Sotatercept at Cycle 9	0.280 1/day Standard Deviation 0.035

Adverse Events

Sotatercept Treatment Period

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Sotatercept Extension Period

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sotatercept Treatment Period n=21 participants at risk Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg SC during Cycle 1. (Each cycle was 21 days.) For the remainder of the 24-week treatment period (Cycle 2 through Cycle 9), participants received an escalated dose of 0.7 mg/kg SC. Dosing occurred once every 3 weeks.	Sotatercept Extension Period n=20 participants at risk Each participant received standard of care (SOC) plus sotatercept at a dose of 0.7 mg/kg SC once every 3 weeks during the 18-month extension period.
Gastrointestinal disorders Haematochezia	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	0.00% 0/20 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
General disorders Complication associated with device	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	0.00% 0/20 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Metabolism and nutrition disorders Hypervolaemia	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	0.00% 0/20 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	5.0% 1/20 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Product Issues Device leakage	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	0.00% 0/20 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	5.0% 1/20 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.

Other adverse events

Measure	Sotatercept Treatment Period n=21 participants at risk Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg SC during Cycle 1. (Each cycle was 21 days.) For the remainder of the 24-week treatment period (Cycle 2 through Cycle 9), participants received an escalated dose of 0.7 mg/kg SC. Dosing occurred once every 3 weeks.	Sotatercept Extension Period n=20 participants at risk Each participant received standard of care (SOC) plus sotatercept at a dose of 0.7 mg/kg SC once every 3 weeks during the 18-month extension period.
Blood and lymphatic system disorders Polycythaemia	14.3% 3/21 • Number of events 9 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	25.0% 5/20 • Number of events 7 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Gastrointestinal disorders Nausea	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	20.0% 4/20 • Number of events 4 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Gastrointestinal disorders Vomiting	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
General disorders Chest pain	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	20.0% 4/20 • Number of events 4 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
General disorders Complication associated with device	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
General disorders Fatigue	14.3% 3/21 • Number of events 4 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
General disorders Pain	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	5.0% 1/20 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
General disorders Peripheral swelling	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	15.0% 3/20 • Number of events 4 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Infections and infestations COVID-19	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Infections and infestations Herpes zoster	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Infections and infestations Upper respiratory tract infection	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Injury, poisoning and procedural complications Contusion	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Metabolism and nutrition disorders Gout	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 3 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Metabolism and nutrition disorders Increased appetite	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	0.00% 0/20 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 3/21 • Number of events 3 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	0.00% 0/20 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/21 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 3/21 • Number of events 3 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	25.0% 5/20 • Number of events 7 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Nervous system disorders Dizziness	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 4 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Nervous system disorders Headache	14.3% 3/21 • Number of events 4 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	15.0% 3/20 • Number of events 3 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Nervous system disorders Migraine	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	5.0% 1/20 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	25.0% 5/20 • Number of events 6 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.5% 2/21 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	5.0% 1/20 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Skin and subcutaneous tissue disorders Rash	9.5% 2/21 • Number of events 3 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 2 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
Skin and subcutaneous tissue disorders Vitiligo	4.8% 1/21 • Number of events 1 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.	10.0% 2/20 • Number of events 6 • Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period. The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor will comply with the requirements for publication of study results. In accordance with standard editorial and ethical practice, the sponsor will generally support publication.
• Publication restrictions are in place

Restriction type: OTHER