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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03496207




Registration number
NCT03496207
Ethics application status
Date submitted
29/03/2018
Date registered
12/04/2018
Date last updated
28/08/2019

Titles & IDs
Public title
A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH)
Scientific 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)
Secondary ID [1] 0 0
2017-004738-27
Secondary ID [2] 0 0
A011-09
Universal Trial Number (UTN)
Trial acronym
PULSAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Sotatercept

Placebo Comparator: Placebo - Placebo SC every 21 days plus SOC for 24 weeks

Experimental: Sotatercept 0.3 mg/kg - Sotatercept, 0.3 mg/kg SC every 21 days plus SOC for 24 weeks

Experimental: Sotatercept 0.7 mg/kg - Sotatercept, 0.7 mg/kg SC every 21 days plus SOC for 24 weeks


Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: Sotatercept
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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in Pulmonary Vascular Resistance (PVR) as measured by right heart catheterization
Timepoint [1] 0 0
From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168)
Secondary outcome [1] 0 0
Change from baseline in 6-Minute Walk Distance (6MWD)
Timepoint [1] 0 0
From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168)
Secondary outcome [2] 0 0
Change from baseline in amino-terminal brain natriuretic propeptide (NT-proBNP)
Timepoint [2] 0 0
From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168)
Secondary outcome [3] 0 0
Change from baseline in tricuspid annular plane systolic excursion (TAPSE) by echocardiography (ECHO)
Timepoint [3] 0 0
From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168)
Secondary outcome [4] 0 0
Change from baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) patient-reported outcome (PRO) score - The CAMPHOR questionnaire contains 65 items in total, 25 relating to symptoms, 15 relating to activities, and 25 relating to Quality of Life (QoL). It is negatively weighted; a higher score indicates worse QoL and greater functional limitation. Symptom and QoL items are both scored out of 25: "yes/true" scores 1 and "no/not true" scores 0. Activity items have three possible responses (score 0-2), giving a score out of 30.
Timepoint [4] 0 0
From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168)
Secondary outcome [5] 0 0
Change from baseline in 36-Item Short Form Health Survey (SF-36) patient-reported outcome (PRO) score - The SF-36 questionnaire is a 36-item, patient-reported survey of patient health. The questionnaire consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Timepoint [5] 0 0
From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168)

Eligibility
Key inclusion criteria
1. Age = 18 years

2. 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

- Heritable PAH

- Drug- or toxin-induced PAH

- PAH associated with connective tissue disease

- PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1
year following shunt repair

3. Symptomatic pulmonary hypertension classified as WHO functional class II or III

4. Screening RHC documenting a minimum PVR of = 400 dyn·sec/cm5 (5 Wood units)

5. Pulmonary function tests (PFTs) within 6 months prior to Screening as follows:

1. Total lung capacity (TLC) > 70% predicted; or if between 60 to70% 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

2. Forced expiratory volume (first second) (FEV1)/ forced vital capacity (FVC) > 70%
predicted

6. 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),

7. No contraindication per investigator for RHC during the study

8. 6MWD = 150 and = 550 meters repeated twice at Screening and both values within 15% of
each other, calculated from the highest value

9. PAH therapy at stable (per investigator) dose levels of SOC therapies
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g,
diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to study visit C1D1

2. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine,
vasopressin) within 30 days prior to study visit C1D1

3. History of atrial septostomy within 180 days prior to Screening

4. History of more than mild obstructive sleep apnea that is untreated

5. 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)

6. History of human immunodeficiency virus infection-associated PAH

7. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536)

8. 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

9. Systolic BP < 90 mmHg during Screening or at baseline

10. History of known pericardial constriction

11. Personal or family history of long QTc syndrome or sudden cardiac death

12. History of restrictive or congestive cardiomyopathy

13. 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.

14. 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)

15. Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per
investigator assessment

16. Significant (= 2+ regurgitation) mitral regurgitation (MR) or aortic regurgitation
(AR) valvular disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,New South WhalesQLD,WA
Recruitment hospital [1] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [4] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2305 - New Lambton
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Brazil
State/province [11] 0 0
Minas Gerais
Country [12] 0 0
Brazil
State/province [12] 0 0
Riogrande Do Sul
Country [13] 0 0
Brazil
State/province [13] 0 0
Santa Catarina
Country [14] 0 0
Brazil
State/province [14] 0 0
Sao Paulo
Country [15] 0 0
France
State/province [15] 0 0
Hérault
Country [16] 0 0
France
State/province [16] 0 0
Le Kremlin-Bicêtre
Country [17] 0 0
France
State/province [17] 0 0
Saint-Étienne
Country [18] 0 0
Germany
State/province [18] 0 0
Bayern,
Country [19] 0 0
Germany
State/province [19] 0 0
Niedersachsen
Country [20] 0 0
Germany
State/province [20] 0 0
Sachsen-Anhalt
Country [21] 0 0
Germany
State/province [21] 0 0
Sachsen
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Israel
State/province [23] 0 0
Ashkelon
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Petach-Tikva
Country [26] 0 0
Israel
State/province [26] 0 0
Safed
Country [27] 0 0
Spain
State/province [27] 0 0
Cantabria
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Pontevedra
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Acceleron Pharma, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 6 months in the Placebo-Controlled Treatment
Period, and then will be eligible to enroll into an 18- month Extension Period during which
all participants will receive sotatercept. All treated patients will be also undergo
follow-up period after last study drug treatment.
Trial website
https://clinicaltrials.gov/show/NCT03496207
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications