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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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:2017-004738-27
    Sponsor's Protocol Code Number:A011-09
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-08-03
    Trial results View 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 ConcernedGermany - PEI
    A.2EudraCT number2017-004738-27
    A.3Full title of the trial
    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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 Study of Sotatercept for the Treatment of PAH
    A.4.1Sponsor's protocol code numberA011-09
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03496207
    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 pointJanethe Pena
    B.5.3 Address:
    B.5.3.1Street Address128 Sidney Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+16179096241
    B.5.6E-mailjpena@acceleronpharma.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 No
    D.2.5.1Orphan drug designation number
    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 placeboSolution 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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10077739
    E.1.2Term Pulmonary arterial hypertension WHO functional class I
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Placebo-Controlled Treatment Period
    -To evaluate the effect on PVR in WHO functional class II-III PAH patients treated with sotatercept plus SOC compared with placebo plus SOC
    Extension Period
    - To evaluate the disease modifying effect of sotatercept and additional efficacy analysis
    -To evaluate the long-term safety of sotatercept in WHO functional class II-III PAH patients
    E.2.2Secondary objectives of the trial
    Placebo-Controlled Treatment Period
    To assess the effects of sotatercept plus SOC on functional and pharmacodynamic endpoints in patients with PAH compared with placebo plus SOC
    Extension Period
    To evaluate the disease modifying effect of sotatercept and additional
    efficacy analysis
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participants must satisfy all of the following criteria to be enrolled in the study:
    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:
    o Idiopathic
    o Heritable PAH
    o Drug- or toxin-induced PAH
    o PAH associated with connective tissue disease
    o 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. Baseline RHC performed within 10 days prior to C1D1 visit during the
    Screening Period documenting a minimum PVR of ≥ 400 dyn·sec/cm5 (5 Wood units)
    5. Pulmonary function tests (PFTs) within 6 months prior to Screening Visit as follows:
    a. 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;
    b. 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 during Screening Period 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 as defined in the protocol for at least 90 days prior to C1D1.
    10. Females of childbearing potential must:
    a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study and until eight weeks after the last dose of the study drug.
    b. If sexually active, have used and agree to continue to use highly effective contraception without interruption, for at least 28 days prior to starting investigational product during the study therapy (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment.
    c. Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 112 days after the last dose of study treatment.
    Male participants must:
    a. Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (for example, 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 112 days following investigational product discontinuation, even if he has undergone a successful vasectomy. (see Appendix 6 for additional contraceptive information).
    b. Refrain from donating blood or sperm for the duration of the study and for 112 days after the last dose of study treatment.
    E.4Principal exclusion criteria
    Participants will be excluded from the study if they meet any of the following criteria:
    1. Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g, diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to C1D1
    2. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to C1D1
    3. History of atrial septostomy within 180 days prior to Screening Visit
    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. 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).
    9. 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
    10. Systolic BP < 90 mmHg during Screening Visit or at baseline (C1D1)
    11. History of known pericardial constriction
    12. ECG with QTcF >480 msec during Screening Period or C1D1
    13. Personal or family history of long QTc syndrome or sudden cardiac death
    14. Cerebrovascular accident (CVA) within 3 months of C1D1
    15. History of restrictive or congestive cardiomyopathy
    16. 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
    17. 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 Screening Visit.
    18. Acutely decompensated heart failure within 30 days prior to C1D1, as per investigator assessment
    19. Significant (≥ 2+ regurgitation) mitral regurgitation (MR) or aortic regurgitation (AR) valvular disease
    20. Any of the following clinical laboratory values during the Screening Period prior to C1D1:
    a. Baseline Hgb > 16 g/dL
    b. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 3X upper limit of normal (ULN) or total bilirubin > 1.5X ULN within 28 days of C1D1
    c. White blood cell (WBC) count < 4000/mm3
    d. Platelets < 100,000/μL
    e. Absolute neutrophil count (ANC) < 1500/mm3
    21. 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
    22. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product
    23. Major surgery within 8 weeks prior to C1D1. Participants must have completely recovered from any previous surgery prior to C1D1.
    24. Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months
    25. Weight > 140 kg at Screening
    31. History of renal disease, including:
    a. Chronic renal disease at any time prior to screening; or
    b. Any episode of acute renal failure, with or without a prior history of renal disease, occurring within the 3 months prior to screening in which acute dialysis (e.g., intermittent hemodialysis or continuous veno-venous hemofiltration) was required
    E.5 End points
    E.5.1Primary end point(s)
    Placebo-Controlled Treatment Period
    -Change in PVR at 24 weeks (C9D1A) vs screening PVR
    Extension Period
    Change from baseline in PVR at Cycle 25 (or next cycles up to Cycle 33)
    for the Delayed-Start efficacy analysis
    - Change from baseline in PVR at Cycle 25 (or next cycles up to Cycle 33) for the Placebo - Crossed efficacy analysis
    -Safety and tolerability assessments based on adverse events (AEs) clinical laboratory values, vital signs
    E.5.1.1Timepoint(s) of evaluation of this end point
    Treatment Period
    -At 24 weeks vs baseline
    Extension Period
    -During the extension period
    E.5.2Secondary end point(s)
    Placebo-Controlled Treatment Period
    Key Secondary Endpoint
    -Change in 6MWD at 24 weeks (C9D1A) vs baseline (screening C1D1).
    Other Secondary Endpoints:
    -Change in NT-proBNP at 24 weeks (C9D1A) vs C1D1.
    -Change in TAPSE at 24 weeks (C9D1) vs C1D1.
    Extension Period
    - Change from baseline in 6MWD at Cycle 25 (or next cycles up to Cycle 33) for the Delayed-Start efficacy analysis
    - Change from baseline in 6MWD at Cycle 25 (or next cycles up to Cycle 33) for the Placebo - Crossed efficacy analysis
    E.5.2.1Timepoint(s) of evaluation of this end point
    Key Secondary Endpoint
    -At 24 weeks vs baseline
    Other Secondary Endpoints:
    -At 24 weeks vs baseline
    -At 24 weeks vs baseline
    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 Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 trial3
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Australia
    Belgium
    Brazil
    France
    Germany
    Israel
    Spain
    United Kingdom
    United States
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months3
    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: 100
    F.1.3Elderly (>=65 years) No
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 70
    F.4.2.2In the whole clinical trial 100
    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 Decision2018-08-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-08-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-03-09
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