Pulmonary Arterial HypertensionPhase 2PULSARNCT03496207
A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH)
A Phase 2 study testing Sotatercept and SOC in people with Pulmonary Arterial Hypertension, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 43 sites in 8 countries.
Trial summary
Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH). Eligible participants will receive study treatment for 24 weeks during the placebo-controlled treatment period, and then will be eligible to enroll into a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Sotatercept and SOC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 43 sitesin 8 countries
- Study dates
- 13 Jun 2018to 9 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Documented diagnostic right heart catheterization (RHC) at any time prior to Screening confirming diagnosis of WHO diagnostic pulmonary hypertension Group I: PAH in any of the following subtypes:
- Idiopathic ii. Heritable PAH iii. Drug- or toxin-induced PAH iv. PAH associated with connective tissue disease v. PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair
- Symptomatic pulmonary hypertension classified as WHO functional class II or III
- Screening RHC documenting a minimum PVR of ≥400 dyn·sec/cm5 (5 Wood units)
- Pulmonary function tests (PFTs) within 6 months prior to Screening as follows:
Show all 12Show fewer
- Total lung capacity (TLC) >70% predicted; or if between 60 to 70% predicted, or not possible to be determined, confirmatory high-resolution computed tomography (CT) indicating no more than mild interstitial lung disease (ILD), per investigator interpretation, or
- Forced expiratory volume (first second) (FEV1)/ forced vital capacity (FVC) >70% predicted
- Ventilation-perfusion (VQ) scan (or, if unavailable a negative CT pulmonary angiogram [CTPA] result, or pulmonary angiography result), any time prior to Screening Visit or conducted during the Screening Period, with normal or low probability result),
- No contraindication per investigator for RHC during the study
- 6MWD ≥150 and ≤550 meters repeated twice at Screening and both values within 15% of each other, calculated from the highest value
- PAH therapy at stable (per investigator) dose levels of SOC therapies
Who cannot join
- Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g, diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to study visit Cycle 1 Day 1 (C1D1)
- Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to study visit C1D1
- History of atrial septostomy within 180 days prior to Screening
- History of more than mild obstructive sleep apnea that is untreated
- Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A-C)
- History of human immunodeficiency virus infection-associated PAH
Show all 36Show fewer
- Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536)
- Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to C1D1 or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible).
- Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) >160 mm Hg or sitting diastolic blood pressure >100 mm Hg during Screening Visit after a period of rest
- Systolic BP <90 mmHg during Screening or at baseline
- History of known pericardial constriction
- Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) >480 msec during Screening Period or C1D1
- Personal or family history of long QTc syndrome or sudden cardiac death
- Cerebrovascular accident within 3 months of C1D1
- History of restrictive or congestive cardiomyopathy
- Left ventricular ejection fraction (LVEF) <45% on historical echocardiogram (ECHO) within 6 months prior to Screening Period (or done as a part of the Screening Period) or pulmonary capillary wedge pressure (PCWP) >15 mmHg as determined in the Screening Period RHC.
- Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain)
- Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per investigator assessment
- Significant (≥2+ regurgitation) mitral regurgitation (MR) or aortic regurgitation (AR) valvular disease
- Any of the following clinical laboratory values during the Screening Period prior to C1D1:
- Baseline Hgb >16.0 g/dL
- Serum alanine aminotransferase or aspartate aminotransferase levels >3X upper limit of normal (ULN) or total bilirubin >1.5X ULN within 28 days of C1D1
- Estimated glomerular filtration rate <30 ml/min/1.73m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of C1D1 or required renal replacement therapy within 90 days
- WBC count <4000/mm3
- Platelets <100,000/μL
- Absolute neutrophil count <1500/mm3
- History of opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia) within 6 months prior to Screening; serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to Screening
- History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
- Major surgery within 8 weeks prior to C1D1. Participants must have completely recovered from any previous surgery prior to C1D1.
- Prior heart or heart-lung transplants or life expectancy of <12 month
- Pregnant or breastfeeding females
- If on corticosteroids, and at any time in the last 30 days prior to the Screening Period: have been receiving doses of >20 mg/day of prednisone (or equivalent) or on a new or changing dose of ≤20 mg/day; only participants receiving stable doses of ≤20 mg prednisone (or equivalent) in last 30 days prior to the Screening Period permitted in the study
- History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤2 squamous cell carcinomas of the skin
- History of clinically significant (as determined by the investigator) non-PAH related cardiac, endocrine, hematologic, hepatic, (auto)immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study. Autoimmune diseases are excluded with the exception of those related to PAH etiologies included in this study.
- Participation in another clinical trial involving intervention with another investigational drug, approved therapy for investigational use, or investigational device within 4 weeks prior to C1D1, or if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer
- Weight >140 kg at Screening
Trial locations and contacts
43 sites in 8 countries.
43 sites in 8 countries
United States12 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Hospital
Aurora, Colorado, 80045
Medical University of South Carolina
Charleston, South Carolina, 29425
Lindner Clinical Trial Center
Cincinnati, Ohio, 45129
UF Health Shands Hospital
Gainesville, Florida, 32610
Houston Methodist Hospital
Houston, Texas, 77030
University of Kansas Medical Center
Kansas City, Kansas, 66160
Pulmonary Associates, PA
Phoenix, Arizona, 85006
Arizona Pulmonary Specialists
Phoenix, Arizona, 85012
Banner-University Medical Center Phoenix
Phoenix, Arizona, 85381
University of California, San Francisco Medical Center
San Francisco, California, 94143
University of Arizona
Tucson, Arizona, 85724
Brazil6 sites
Hospital Madre Teresa
Belo Horizonte, Minas Gerais, 30430
Hospital Dia do Pulmão
Blumenau, Santa Catarina, 89010
Instituto do Coracao - HCFMUSP
Cerqueira César, 05403-900
Hospital Sao Lucas da PUCRS
Jardim Botânico, 05403-900
Irmandade Da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Riogrande Do Sul, 90035
Hospital São Paulo
São Paulo, 04037
Israel5 sites
Barzilai Medical Center
Ashkelon, 78278
Lady Davis Carmel Medical Center
Haifa, 34362
Meir Medical Center
Kefar Sava, 4428100
Rabin Medical Center - PPDS
Petah Tikva, 49100
Chaim Sheba Medical Center
Ramat Gan, 52621
Spain5 sites
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, 28222
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Australia4 sites
Prince Charles Hospital
Chermside, Queensland, 4032
St. Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
John Hunter Hospital
New Lambton, New South Whales, 2305
Westmead Hospital
Westmead, New South Wales, 2145
France4 sites
CHU Michallon
La Tronche, 38700
Centre Hospitalier Universitaire de Bicêtre
Le Kremlin-Bicêtre, 94275
Hôpital Arnaud de Villeneuve
Montpellier, Hérault, 34295
Centre Hospitalier Universitaire de Saint Etienne
Saint-Etienne, 42055
Germany4 sites
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307
Universitatsklinikum Halle (Saale)
Halle, Saxony-Anhalt, 06120
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Universitatsklinikum Leipzig
Leipzig, Saxony, 04103
United Kingdom3 sites
Golden Jubilee National Hospital - PPDS
Clydebank, G81 4DY
Royal Free London NHS Foundation Trust
London, NW32QG
Imperial College Healthcare NHS Trust
London, W2 1NY
About this study
Official title: A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study to Compare the Efficacy and Safety of Sotatercept (ACE-011) Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)
Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH). Eligible participants will receive study treatment for 24 weeks during the placebo-controlled treatment period, and then will be eligible to enroll into a 30-month extension period during which all participants will receive sotatercept. All treated patients will also undergo a follow-up period after last study drug treatment.
Read the detailed description
This is a Phase 2, double-blind, randomized, placebo-controlled, parallel-group study of sotatercept plus standard of care (SOC) versus placebo plus SOC in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 3:3:4 ratio to receive placebo, sotatercept 0.3 mg/kg, or sotatercept 0.7 mg/kg by subcutaneous (SC) injection every 21 days for a period of 24 weeks in the placebo-controlled treatment period of the study while on SOC therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), quality of life questionnaires, echocardiographic parameters, and safety. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 30-month extension period in which sotatercept-treated participants will receive their latest dose level of sotatercept SC every 21 days and placebo-treated participants will be re-randomized 1:1 to receive sotatercept 0.3 mg/kg SC or sotatercept 0.7 mg/kg SC every 21 days while on SOC therapy.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Placebo, Sotatercept, SOC
- Keywords
- PAH
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo
SotaterceptDrug
Also called ACE-011
Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1.
SOCOther
SOC therapy refers to approved PAH-specific medications and may consist of monotherapy or combination therapy with endothelin-receptor antagonists, phosphodiesterase 5 (PDE5) inhibitors, soluble guanylate cyclase stimulators, and/or prostacyclin analogues or receptor agonists.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive placebo plus SOC by SC injection during the 24-week treatment period. Dosing will occur once every 3 weeks. Receives: Drug: Placebo; Other: SOC |
| Sotatercept 0.3 mg/kg | Experimental | Participants will receive sotatercept 0.3 mg/kg plus SOC by SC injection during the 24-week treatment period. Per protocol, participants may have their doses titrated. Dosing will occur once every 3 weeks. Receives: Drug: Sotatercept; Other: SOC |
| Sotatercept 0.7 mg/kg | Experimental | Participants will receive sotatercept 0.7 mg/kg plus SOC by SC injection during the 24-week treatment period. Per protocol, participants may have their doses titrated. Dosing will occur once every 3 weeks. Receives: Drug: Sotatercept; Other: SOC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and at 24 weeks.
Measured: Baseline and 24 weeks
Extension Period: Change From Baseline in PVR (Delayed-Start Analysis)
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Measured: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Change From Baseline in PVR (Placebo-Crossed Analysis)
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Measured: Baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs)
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.
Measured: Up to approximately 32 months
Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE
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.
Measured: Up to 30 months
Secondary outcomes (18)
Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (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.
Measured: Baseline and 24 weeks
Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (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.
Measured: Baseline and 24 Weeks
Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks
Each participant's TAPSE, which is commonly used to evaluate tricuspid valve annulus movement as an indicator of right heart function, was measured by echocardiography at baseline and 24 weeks.
Measured: Baseline and 24 weeks
Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9
The CAMPHOR is participant-reported questionnaire that contains 65 items in total, 25 relating to symptoms, 25 relating to quality of life (QoL), and 15 relating to activities. Symptom items are scored from 0-25, with a higher score indicating worse symptoms. QoL items are also scored from 0-25, with a higher score indicating a worse QoL and greater functional limitation. Activity items are scored from 0-30, with a higher score indicating poorer functioning. The combined score is obtained by summing up the symptoms score, QoL score and activity score. The lowest combined score possible is 0, while the highest combined score possible is 80. Each participant's CAMPHOR score was recorded at baseline and on Day 1 of Cycle 9.
Measured: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score
The SF-36 questionnaire is a participant-reported survey of a participant's health. The survey evaluates 8 aspects of functional health and well-being that relate to either physical health or mental health. The physical component summary is based primarily on physical functioning, bodily pain, and general health. The mental component summary encompasses vitality, social functioning, and emotional and mental health. Total scores for the physical component range from 0-100, with 100 representing the highest level of physical functioning. The total scores for the mental component also range from 0-100, with 100 representing the highest level of mental functioning. Each participant's SF-36 was recorded at baseline and on Day 1 of Cycle 9. Each cycle was 21 days.
Measured: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (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).
Measured: Up to 24 weeks
Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks
The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension.
Measured: Baseline and 24 Weeks
Base Study: Number of Participants Who Experienced One or More AEs
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.
Measured: Up to 24 weeks
Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE
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.
Measured: Up to 24 weeks
Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9
Each participant's BMI was measured at baseline and at 24 weeks.
Measured: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9
Each participant's systolic and diastolic blood pressure was taken at baseline and on Day 1 of Cycle 9. Each cycle was 21 days.
Measured: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in Respiratory Rate at Cycle 9
Each participant's respiratory rate (number of breaths per minute) was measured at baseline and on Day 1 of Cycle 9. Each cycle was 21 days.
Measured: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in QTcF Interval at Cycle 9
Each participant's QTcF Interval was measured at baseline and on Day 1 of Cycle 9.
Measured: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Maximum Plasma Concentration (Cmax) of Sotatercept
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Based on population pharmacokinetic (PopPK) modeling of previous sotatercept studies, Cmax occurs at Day 8 of Cycle 1 after a sotatercept dose is given. The sotatercept concentration at Day 8 of Cycle 1 (each cycle was 21 days) is presented here as Cmax.
Measured: Day 8 of Cycle 1 (Each cycle was 21 days.)
Extension Period: Change From Baseline in 6MWD (Delayed-Start Analysis)
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 the timepoint at which the third RCH was performed. This occurred between Month 18 and Month 24, at which time each participant's 6MWD was also measured. An increase in the distance walked during the 6MWT indicates improvement in basic mobility.
Measured: Baseline and the timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Change From Baseline in 6MWD (Placebo-Crossed Analysis)
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 the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's 6MWD was also measured. An increase in the distance walked during the 6MWT indicates improvement in basic mobility.
Measured: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Number of Participants Who Experienced an Improvement From Baseline in WHO Functional Class (Delayed-Start Analysis)
The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. Each participant's WHO Functional Class was assessed at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's WHO Functional Class was also assessed.
Measured: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Change From Baseline in WHO Functional Class (Placebo-Crossed Analysis)
The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. Each participant's WHO Functional Class was assessed at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's WHO Functional Class was also assessed.
Measured: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2018
- Study start13 Jun 2018
- Primary completion9 Mar 2022
- Study completion9 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03496207
- Sponsor's protocol ID
- A011-09
- Other IDs
- 2017-004738-27, 2017
- Acronym
- PULSAR
- Status last verified
- Mar 2023
- First submitted
- 29 Mar 2018
- Last updated
- 19 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Ghofrani HA, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, de Oliveira Pena J, Badesch DB. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J. 2023 Jan 6;61(1):2201347. doi: 10.1183/13993003.01347-2022. Print 2023 Jan.
PubMed 36041750Dutta S, Shah R, Singhal S, Singh M, Dholariya S, Chawla S, Katoch C. A systematic review and meta-analysis of safety and efficacy parameters of sotatercept in the therapy of pulmonary arterial hypertension. Expert Opin Drug Saf. 2026 Jun 9:1-13. doi: 10.1080/14740338.2026.2685360. Online ahead of print.
PubMed 42246435Montani D, McLaughlin VV, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Escribano Subias P, Feldman J, Meyer GM, Olsson KM, Coulet F, Manimaran S, Zhao Y, Lau A, de Oliveira Pena J, Badesch DB, Humbert M. Consistent Safety and Efficacy of Sotatercept for Pulmonary Arterial Hypertension in BMPR2 Mutation Carriers and Noncarriers: A Planned Analysis of a Phase II, Double-Blind, Placebo-controlled Clinical Trial (PULSAR). Am J Respir Crit Care Med. 2025 Jun;211(6):1028-1037. doi: 10.1164/rccm.202409-1698OC.
PubMed 40035659Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman A, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, Barnes J, Linde PG, de Oliveira Pena J, Badesch DB; PULSAR Trial Investigators. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2021 Apr 1;384(13):1204-1215. doi: 10.1056/NEJMoa2024277.
PubMed 33789009
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study to Compare the Efficacy and Safety of Sotatercept (ACE-011) Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)
- ClinicalTrials.gov ID
- NCT03496207
- Acronym / sponsor ID
- PULSAR / A011-09
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- PAH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 9 Mar 2022 (actual)
- Study completion
- 9 Mar 2022 (actual)
- First posted
- 12 Apr 2018 (actual)
- Results
- Posted 19 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH). Eligible participants will receive study treatment for 24 weeks during the placebo-controlled treatment period, and then will be eligible to enroll into a 30-month extension period during which all participants will receive sotatercept. All treated patients will also undergo a follow-up period after last study drug treatment.
Detailed description
This is a Phase 2, double-blind, randomized, placebo-controlled, parallel-group study of sotatercept plus standard of care (SOC) versus placebo plus SOC in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 3:3:4 ratio to receive placebo, sotatercept 0.3 mg/kg, or sotatercept 0.7 mg/kg by subcutaneous (SC) injection every 21 days for a period of 24 weeks in the placebo-controlled treatment period of the study while on SOC therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), quality of life questionnaires, echocardiographic parameters, and safety. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 30-month extension period in which sotatercept-treated participants will receive their latest dose level of sotatercept SC every 21 days and placebo-treated participants will be re-randomized 1:1 to receive sotatercept 0.3 mg/kg SC or sotatercept 0.7 mg/kg SC every 21 days while on SOC therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Other: SOCParticipants will receive placebo plus SOC by SC injection during the 24-week treatment period. Dosing will occur once every 3 weeks. |
| Sotatercept 0.3 mg/kg | Experimental | Drug: Sotatercept, Other: SOCParticipants will receive sotatercept 0.3 mg/kg plus SOC by SC injection during the 24-week treatment period. Per protocol, participants may have their doses titrated. Dosing will occur once every 3 weeks. |
| Sotatercept 0.7 mg/kg | Experimental | Drug: Sotatercept, Other: SOCParticipants will receive sotatercept 0.7 mg/kg plus SOC by SC injection during the 24-week treatment period. Per protocol, participants may have their doses titrated. Dosing will occur once every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥18 years
- Documented diagnostic right heart catheterization (RHC) at any time prior to Screening confirming diagnosis of WHO diagnostic pulmonary hypertension Group I: PAH in any of the following subtypes:
- Symptomatic pulmonary hypertension classified as WHO functional class II or III
- Screening RHC documenting a minimum PVR of ≥400 dyn·sec/cm5 (5 Wood units)
- Pulmonary function tests (PFTs) within 6 months prior to Screening as follows:
Key exclusion criteria (36 listed)
- Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g, diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to study visit Cycle 1 Day 1 (C1D1)
- Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to study visit C1D1
- History of atrial septostomy within 180 days prior to Screening
- History of more than mild obstructive sleep apnea that is untreated
- Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A-C)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo | Drug | Placebo |
| SotaterceptAlso: ACE-011Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1. | Drug | Sotatercept 0.3 mg/kg, Sotatercept 0.7 mg/kg |
| SOCSOC therapy refers to approved PAH-specific medications and may consist of monotherapy or combination therapy with endothelin-receptor antagonists, phosphodiesterase 5 (PDE5) inhibitors, soluble guanylate cyclase stimulators, and/or prostacyclin analogues or receptor agonists. | Other | Placebo, Sotatercept 0.3 mg/kg, Sotatercept 0.7 mg/kg |
Primary outcome
Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks
Time frame: Baseline and 24 weeks
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and at 24 weeks.
Extension Period: Change From Baseline in PVR (Delayed-Start Analysis)
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Extension Period: Change From Baseline in PVR (Placebo-Crossed Analysis)
Time frame: Baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs)
Time frame: Up to approximately 32 months
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.
Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to 30 months
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.
18 secondary outcomes
Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
Time frame: Baseline and 24 weeks
Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks
Time frame: Baseline and 24 Weeks
Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks
Time frame: Baseline and 24 weeks
Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH)
Time frame: Up to 24 weeks
Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks
Time frame: Baseline and 24 Weeks
Base Study: Number of Participants Who Experienced One or More AEs
Time frame: Up to 24 weeks
Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to 24 weeks
Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in Respiratory Rate at Cycle 9
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Change From Baseline in QTcF Interval at Cycle 9
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Base Study: Maximum Plasma Concentration (Cmax) of Sotatercept
Time frame: Day 8 of Cycle 1 (Each cycle was 21 days.)
Extension Period: Change From Baseline in 6MWD (Delayed-Start Analysis)
Time frame: Baseline and the timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Change From Baseline in 6MWD (Placebo-Crossed Analysis)
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Number of Participants Who Experienced an Improvement From Baseline in WHO Functional Class (Delayed-Start Analysis)
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Extension Period: Change From Baseline in WHO Functional Class (Placebo-Crossed Analysis)
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36041750Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Ghofrani HA, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, de Oliveira Pena J, Badesch DB. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J. 2023 Jan 6;61(1):2201347. doi: 10.1183/13993003.01347-2022. Print 2023 Jan.
- Derived from this study: PubMed 42246435Dutta S, Shah R, Singhal S, Singh M, Dholariya S, Chawla S, Katoch C. A systematic review and meta-analysis of safety and efficacy parameters of sotatercept in the therapy of pulmonary arterial hypertension. Expert Opin Drug Saf. 2026 Jun 9:1-13. doi: 10.1080/14740338.2026.2685360. Online ahead of print.
- Derived from this study: PubMed 40035659Montani D, McLaughlin VV, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Escribano Subias P, Feldman J, Meyer GM, Olsson KM, Coulet F, Manimaran S, Zhao Y, Lau A, de Oliveira Pena J, Badesch DB, Humbert M. Consistent Safety and Efficacy of Sotatercept for Pulmonary Arterial Hypertension in BMPR2 Mutation Carriers and Noncarriers: A Planned Analysis of a Phase II, Double-Blind, Placebo-controlled Clinical Trial (PULSAR). Am J Respir Crit Care Med. 2025 Jun;211(6):1028-1037. doi: 10.1164/rccm.202409-1698OC.
- Derived from this study: PubMed 33789009Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman A, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, Barnes J, Linde PG, de Oliveira Pena J, Badesch DB; PULSAR Trial Investigators. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2021 Apr 1;384(13):1204-1215. doi: 10.1056/NEJMoa2024277.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
43 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sotatercept and SOC in people with Pulmonary Arterial Hypertension, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 43 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Brazil, Israel, Spain, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks (time frame: Baseline and 24 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03496207, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2023.