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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-000199-12
    Sponsor's Protocol Code Number:A011-13
    National Competent Authority:Croatia - MIZ
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-02-03
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedCroatia - MIZ
    A.2EudraCT number2021-000199-12
    A.3Full title of the trial
    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.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study of Sotatercept in Newly Diagnosed Intermediate- and High-risk Pulmonary arterial hypertension (PAH) Patients.
    A.3.2Name or abbreviated title of the trial where available
    A Phase 3 Study of Sotatercept in Newly Diagnosed Intermediate- and High-risk PAH Patients
    A.4.1Sponsor's protocol code numberA011-13
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04811092
    A.5.4Other Identifiers
    Name:INDNumber:136150
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAcceleron Pharma Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAcceleron Pharma Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAcceleron Pharma Inc.
    B.5.2Functional name of contact pointJohn Butler
    B.5.3 Address:
    B.5.3.1Street Address126 East Lincoln Ave.; P.O. Box 2000
    B.5.3.2Town/ cityRahway
    B.5.3.3Post codeNJ 07065
    B.5.3.4CountryUnited States
    B.5.4Telephone number5039649504
    B.5.6E-mailjohn.butler2@merck.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/20/2369
    D.3 Description of the IMP
    D.3.1Product nameSotatercept
    D.3.2Product code ACE-011
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSOTATERCEPT
    D.3.9.1CAS number 1001080-50-7
    D.3.9.2Current sponsor codeACE-011
    D.3.9.3Other descriptive nameActRIIA-IgG1Fc
    D.3.9.4EV Substance CodeSUB179718
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboLyophilisate for solution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary Arterial Hypertension (PAH)
    E.1.1.1Medical condition in easily understood language
    Cardiovascular Disease
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10064911
    E.1.2Term Pulmonary arterial hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The objective of this study is to evaluate the effects of sotatercept treatment (plus background PAH therapy) versus placebo (plus background PAH therapy) on TTCW in participants who are newly diagnosed with PAH and are at intermediate or high risk of PAH disease progression.
    E.2.2Secondary objectives of the trial
    not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    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. REVEAL Lite 2 risk score ≥ 6
    5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies 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).Background PAH therapy is further defined in Section 7.2.
    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:
    - 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
    E.4Principal exclusion criteria
    1. Diagnosis of PAH WHO Groups 2, 3, 4, or 5
    2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, 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) > 160 mmHg or sitting diastolic BP > 100 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/m2 (as defined by MDRD equation)
    -Serum alanine aminotransferase aspartate aminotransferase , or 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 biologics prior to the date of signed 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 pulmonary hypertension 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 within 1 year prior to the Screening Visit or pulmonary capillary wedge pressure > 15 mmHg as determined by historical RHC within 12 months 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
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is TTCW, defined as the time from randomization to the first confirmed morbidity event or death. The events that will comprise this endpoint
    include the following:
    • All-cause death
    • Non-planned PAH-related hospitalization of ≥ 24 hours in duration
    • Atrial septostomy
    • Lung transplant
    • Deterioration in performance in exercise testing due to PAH, defined as a decrease in 6MWD from baseline on
    2 consecutive tests (which must be at least 4 hours apart) and at least 1 of the following:
    − Worsening of WHO FC from baseline
    − Signs/symptoms of increased right heart failure
    − Addition of a background PAH therapy or change PAH background therapy, delivery route to parenteral
    All events will be adjudicated by a blinded, independent committee of clinical experts.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be analyzed using a weighted stratified log-rank test with randomization stratification factors as strata. The Cui-Hung-Wang (CHW) method will be used to control the Type I error rate for the primary endpoint. The point estimate of the hazard ratio with 95% CI will be estimated by a Cox regression model stratified by the randomization factors. If there is no increase in the number of events and sample size following the planned interim analysis, then the CHW method will be the same as a conventional analysis of this data using a log-rank test. The Chen-DeMets-Lan method will be used as a supportive analysis to the CHW method.
    E.5.2Secondary end point(s)
    1. Multicomponent improvement endpoint measured by the proportion of participants achieving all of the following at Week 24 relative to baseline:
    -Improvement in 6MWD (increase ≥ 30 m)
    -Improvement in NT-proBNP (decrease in NT-proBNP ≥ 30%) or maintenance/achievement of NT-proBNP level < 300 ng/L
    -Improvement in WHO FC or maintenance of WHO FC II
    2. Proportion of participants who achieve a low REVEAL Lite 2 risk score at Week 24 versus baseline
    3. Proportion of participants who maintain or achieve a low risk score at Week 24 versus baseline using the simplified French
    Risk score calculator
    4. Change from baseline in NT-proBNP levels at Week 24
    5. Proportion of participants who improve in WHO FC or maintain WHO FC II at 24 weeks from baseline
    6. Change from baseline in 6MWD at Week 24
    7. Change from baseline in the Physical Impacts domain score of Pulmonary Arterial Hypertension-Symptoms and Impact (PAH SYMPACT®) at Week 24
    8. Change from baseline in the Cardiopulmonary Symptoms (domain score of PAH-SYMPACT)®® at Week 24
    9. Change from baseline in the Cognitive/Emotional Impacts domain score of PAH-SYMPACT® at Week 24
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA72
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Brazil
    Canada
    Colombia
    Israel
    Korea, Republic of
    New Zealand
    Taiwan
    United States
    Austria
    France
    Poland
    Sweden
    Netherlands
    Spain
    Switzerland
    Czechia
    Germany
    Greece
    Italy
    Belgium
    Croatia
    Denmark
    Ireland
    Portugal
    United Kingdom
    Serbia
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as when the last participant completes the last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 497
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 165
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state23
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 303
    F.4.2.2In the whole clinical trial 662
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-01-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-11
    P. End of Trial
    P.End of Trial StatusOngoing
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