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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04811092




Registration number
NCT04811092
Ethics application status
Date submitted
16/03/2021
Date registered
23/03/2021

Titles & IDs
Public title
Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13)
Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy in Newly Diagnosed Intermediate- and High-risk PAH Patients
Secondary ID [1] 0 0
A011-13
Secondary ID [2] 0 0
7962-005
Universal Trial Number (UTN)
Trial acronym
HYPERION
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 - Sotatercept
Other interventions - Placebo

Placebo comparator: Placebo plus background PAH therapy - Administered subcutaneously (SC) every 21 days plus background PAH therapy

Experimental: Sotatercept plus background PAH therapy - Administered at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously (SC) every 21 days plus background PAH therapy


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

Other interventions: Placebo
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Clinical Worsening
Timepoint [1] 0 0
From time of randomization to the time of first clinical worsening event (Up to approximately 47 months)
Secondary outcome [1] 0 0
Percentage of Participants Achieving the Multicomponent Improvement Endpoint of 6-Minute Walk Distance (6MWD), N-terminal prohormone Btype natriuretic peptide (NT-ProBNP) and World Health Organization (WHO) Functional Class (FC)
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [2] 0 0
Percentage of Participants who Achieved a Low Registry to Evaluate Early and Long Term PAH Disease Management (REVEAL) Lite 2 Risk Score
Timepoint [2] 0 0
Baseline and Week 24
Secondary outcome [3] 0 0
Percentage of Participants who Maintain or Achieve a Low Simplified French Risk Score
Timepoint [3] 0 0
Baseline and Week 24
Secondary outcome [4] 0 0
Change from Baseline in NT-proBNP Levels
Timepoint [4] 0 0
Baseline and Week 24
Secondary outcome [5] 0 0
Percentage of Participants who Improve in WHO FC or Maintain WHO FC II at 24 Weeks from Baseline
Timepoint [5] 0 0
Baseline and Week 24
Secondary outcome [6] 0 0
Change from Baseline in 6MWD
Timepoint [6] 0 0
Baseline and Week 24
Secondary outcome [7] 0 0
Change from Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT)®
Timepoint [7] 0 0
Baseline and Week 24
Secondary outcome [8] 0 0
Change from Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT®
Timepoint [8] 0 0
Baseline and Week 24
Secondary outcome [9] 0 0
Change from Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT®
Timepoint [9] 0 0
Baseline and Week 24

Eligibility
Key inclusion criteria
Eligible participants must meet all of the following criteria to be enrolled in the study:

1. Age = 18 years
2. Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of = 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of = 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes:

* Idiopathic PAH
* Heritable PAH
* Drug/toxin-induced PAH
* PAH associated with connective tissue disease
* PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
3. Symptomatic PAH classified as WHO FC II or III
4. Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score = 6 or Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 risk score =2 (intermediate to-low-risk or above)
5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening
6. Six-minute walk distance = 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value)
7. Females of childbearing potential must meet the following criteria:

* Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing urine or serum pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
* If sexually active with a male partner, have used highly effective contraception without interruption, for at least 28 days prior to starting the investigational product AND agreed to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions) and for 16 weeks (112 days) after discontinuation of study treatment
* Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment
8. Male participants must meet the following criteria:

* Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
* Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment
9. Ability to adhere to study visit schedule and understand and comply with all protocol requirements
10. Ability to understand and provide written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from the study if any of the following criteria are met:

1. Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5
2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary capillary hemangiomatosis
3. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest
5. Baseline systolic BP < 90 mmHg at screening
6. Pregnant or breastfeeding women
7. Any of the following clinical laboratory values at the Screening Visit:

* Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (as defined by MDRD equation)
* Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels > 3 × ULN
* Platelet count < 50,000/mm3 (< 50.0 × 109 /L)
8. Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented informed consent
9. Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
10. History of pneumonectomy
11. Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit
12. Stopped receiving any PH chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
13. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the Screening Visit 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)
14. Untreated more than mild obstructive sleep apnea
15. History of known pericardial constriction
16. History of restrictive or congestive cardiomyopathy
17. History of atrial septostomy within 180 days prior to the Screening Visit
18. Electrocardiogram with Fridericia's corrected QT interval > 500 ms during the Screening Period
19. Personal or family history of long QT syndrome or sudden cardiac death
20. Left ventricular ejection fraction < 50% on historical echocardiogram (ECHO) within 1 year prior to the Screening Visit
21. 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) in the past 6 months prior to the Screening Visit
22. Cerebrovascular accident within 3 months prior to the Screening Visit
23. Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment
24. Significant (= 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
25. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit
26. Has an active malignancy with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or expected, during the study, to be treated with radiation therapy, chemotherapy, and/or surgical intervention, or hormonal treatment

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
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,QLD,SA,TAS,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital ( Site 1106) - Camperdown
Recruitment hospital [2] 0 0
John Hunter Hospital ( Site 1101) - Newcastle
Recruitment hospital [3] 0 0
Prince Charles Hospital ( Site 1104) - Chermside
Recruitment hospital [4] 0 0
Princess Alexandra Hospital ( Site 1108) - Woolloongabba
Recruitment hospital [5] 0 0
Royal Adelaide Hospital ( Site 1109) - Adelaide
Recruitment hospital [6] 0 0
Royal Hobart Hospital ( Site 1107) - Hobart
Recruitment hospital [7] 0 0
Fiona Stanley Hospital ( Site 1103) - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2308 - Newcastle
Recruitment postcode(s) [3] 0 0
4032 - Chermside
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
7000 - Hobart
Recruitment postcode(s) [7] 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
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New Mexico
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
Argentina
State/province [20] 0 0
Buenos Aires
Country [21] 0 0
Argentina
State/province [21] 0 0
Cordoba
Country [22] 0 0
Argentina
State/province [22] 0 0
Santa Fe
Country [23] 0 0
Austria
State/province [23] 0 0
Oberosterreich
Country [24] 0 0
Austria
State/province [24] 0 0
Steiermark
Country [25] 0 0
Austria
State/province [25] 0 0
Tirol
Country [26] 0 0
Austria
State/province [26] 0 0
Wien
Country [27] 0 0
Belgium
State/province [27] 0 0
Bruxelles-Capitale, Region De
Country [28] 0 0
Belgium
State/province [28] 0 0
Vlaams-Brabant
Country [29] 0 0
Brazil
State/province [29] 0 0
Minas Gerais
Country [30] 0 0
Brazil
State/province [30] 0 0
Rio Grande Do Sul
Country [31] 0 0
Brazil
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Sao Paulo
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Canada
State/province [32] 0 0
Alberta
Country [33] 0 0
Canada
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Manitoba
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Canada
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Ontario
Country [35] 0 0
Canada
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Quebec
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Colombia
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Antioquia
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Colombia
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Cundinamarca
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Colombia
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Valle Del Cauca
Country [39] 0 0
Croatia
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Splitsko-dalmatinska Zupanija
Country [40] 0 0
Croatia
State/province [40] 0 0
Zagrebacka Zupanija
Country [41] 0 0
Czechia
State/province [41] 0 0
Praha 4
Country [42] 0 0
Czechia
State/province [42] 0 0
Praha 2
Country [43] 0 0
Denmark
State/province [43] 0 0
Hovedstaden
Country [44] 0 0
Denmark
State/province [44] 0 0
Midtjylland
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France
State/province [45] 0 0
Alpes-Maritimes
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France
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Auvergne
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France
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Bas-Rhin
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France
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Bretagne
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France
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Calvados
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France
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Gironde
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France
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Haute-Garonne
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France
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Indre-et-Loire
Country [53] 0 0
France
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Isere
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France
State/province [54] 0 0
Loire-Atlantique
Country [55] 0 0
France
State/province [55] 0 0
Loire
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France
State/province [56] 0 0
Maine-et-Loire
Country [57] 0 0
France
State/province [57] 0 0
Meurthe-et-Moselle
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France
State/province [58] 0 0
Val-de-Marne
Country [59] 0 0
France
State/province [59] 0 0
Vienne
Country [60] 0 0
Germany
State/province [60] 0 0
Baden-Wurttemberg
Country [61] 0 0
Germany
State/province [61] 0 0
Bayern
Country [62] 0 0
Germany
State/province [62] 0 0
Niedersachsen
Country [63] 0 0
Germany
State/province [63] 0 0
Nordrhein-Westfalen
Country [64] 0 0
Germany
State/province [64] 0 0
Saarland
Country [65] 0 0
Germany
State/province [65] 0 0
Sachsen-Anhalt
Country [66] 0 0
Germany
State/province [66] 0 0
Sachsen
Country [67] 0 0
Germany
State/province [67] 0 0
Berlin
Country [68] 0 0
Greece
State/province [68] 0 0
Attiki
Country [69] 0 0
Greece
State/province [69] 0 0
Thessaloniki
Country [70] 0 0
Israel
State/province [70] 0 0
Ashdod
Country [71] 0 0
Israel
State/province [71] 0 0
Haifa
Country [72] 0 0
Israel
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Jerusalem
Country [73] 0 0
Israel
State/province [73] 0 0
Ramat Gan
Country [74] 0 0
Italy
State/province [74] 0 0
Friuli-Venezia Giulia
Country [75] 0 0
Italy
State/province [75] 0 0
Lombardia
Country [76] 0 0
Italy
State/province [76] 0 0
Monza E Brianza
Country [77] 0 0
Italy
State/province [77] 0 0
Napoli
Country [78] 0 0
Italy
State/province [78] 0 0
Roma
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Incheon
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Kyonggi-do
Country [81] 0 0
Korea, Republic of
State/province [81] 0 0
Seoul
Country [82] 0 0
Netherlands
State/province [82] 0 0
Gelderland
Country [83] 0 0
Netherlands
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Limburg
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Netherlands
State/province [84] 0 0
Noord-Holland
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Netherlands
State/province [85] 0 0
Zuid-Holland
Country [86] 0 0
New Zealand
State/province [86] 0 0
Waikato
Country [87] 0 0
Poland
State/province [87] 0 0
Malopolskie
Country [88] 0 0
Poland
State/province [88] 0 0
Mazowieckie
Country [89] 0 0
Portugal
State/province [89] 0 0
Setubal
Country [90] 0 0
Portugal
State/province [90] 0 0
Coimbra
Country [91] 0 0
Portugal
State/province [91] 0 0
Lisboa
Country [92] 0 0
Serbia
State/province [92] 0 0
Juznobacki Okrug
Country [93] 0 0
Serbia
State/province [93] 0 0
Nisavski Okrug
Country [94] 0 0
Serbia
State/province [94] 0 0
Sumadijski Okrug
Country [95] 0 0
Serbia
State/province [95] 0 0
Beograd
Country [96] 0 0
Spain
State/province [96] 0 0
Cantabria
Country [97] 0 0
Spain
State/province [97] 0 0
Islas Baleares
Country [98] 0 0
Spain
State/province [98] 0 0
Madrid
Country [99] 0 0
Spain
State/province [99] 0 0
Barcelona
Country [100] 0 0
Spain
State/province [100] 0 0
Salamanca
Country [101] 0 0
Spain
State/province [101] 0 0
Toledo
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Sweden
State/province [102] 0 0
Skane Lan
Country [103] 0 0
Sweden
State/province [103] 0 0
Uppsala Lan
Country [104] 0 0
Sweden
State/province [104] 0 0
Vasterbottens Lan
Country [105] 0 0
Switzerland
State/province [105] 0 0
Zurich
Country [106] 0 0
Taiwan
State/province [106] 0 0
Kaohsiung
Country [107] 0 0
Taiwan
State/province [107] 0 0
Taichung
Country [108] 0 0
Taiwan
State/province [108] 0 0
Tainan
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Cambridgeshire
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Derbyshire
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Glasgow City
Country [112] 0 0
United Kingdom
State/province [112] 0 0
London, City Of
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.