Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   41465   clinical trials with a EudraCT protocol, of which   6815   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-003803-22
    Sponsor's Protocol Code Number:AG348-C-007
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-02-08
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2017-003803-22
    A.3Full title of the trial
    An Open-Label Study to Evaluate the Efficacy and Safety of AG-348 in Regularly Transfused Adult Subjects With Pyruvate Kinase (PK) Deficiency
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open-Label Study to Evaluate the Efficacy and Safety of AG-348 in Regularly Transfused Adult Subjects With Pyruvate Kinase (PK) Deficiency
    A.4.1Sponsor's protocol code numberAG348-C-007
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03559699
    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 SponsorAgios Pharmaceuticals, 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 supportAgios Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAgios Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointDirector, Scientific Communications
    B.5.3 Address:
    B.5.3.1Street Address88 Sidney Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139-4169
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1844633 2332
    B.5.6E-mailmedinfo@agios.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 nameAG-348 sulfate hydrate
    D.3.2Product code AG-348
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMitapivat
    D.3.9.1CAS number 2151847-10-6
    D.3.9.2Current sponsor codeAG-348 sulfate hydrate
    D.3.9.3Other descriptive nameAGI-1480, AGX-0841, AG-348, AG-348 hemisulfate
    D.3.9.4EV Substance CodeSUB181978
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 2
    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 nameAG-348 sulfate hydrate
    D.3.2Product code AG-348
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMitapivat
    D.3.9.1CAS number 2151847-10-6
    D.3.9.2Current sponsor codeAG-348 sulfate hydrate
    D.3.9.3Other descriptive nameAGI-1480, AGX-0841, AG-348, AG-348 hemisulfate
    D.3.9.4EV Substance CodeSUB181978
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 3
    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 nameAG-348 sulfate hydrate
    D.3.2Product code AG-348
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMitapivat
    D.3.9.1CAS number 2151847-10-6
    D.3.9.2Current sponsor codeAG-348 sulfate hydrate
    D.3.9.3Other descriptive nameAGI-1480, AGX-0841, AG-348, AG-348 hemisulfate
    D.3.9.4EV Substance CodeSUB181978
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pyruvate Kinase Deficiency
    E.1.1.1Medical condition in easily understood language
    Lack of Pyruvate Kinase enzyme
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10037682
    E.1.2Term Pyruvate kinase deficiency anaemia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic 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 primary objective of the study is to evaluate the efficacy of treatment with AG-348, as assessed by the reduction in transfusion burden.
    E.2.2Secondary objectives of the trial
    The secondary objective of this study is to evaluate the safety of treatment with AG-348.

    Exploratory objectives are:
    • To determine the effect of AG-348 on markers of hemolysis, erythropoietic activity, and other indicators of clinical activity
    • To determine the effect of AG-348 on markers of iron metabolism and indicators of iron overload
    • To determine the effect of AG-348 on health-related quality of life (HRQoL), as determined using patient-reported outcomes
    • To evaluate the pharmacokinetics of AG-348 after oral administration
    • To evaluate the relationship of AG-348 pharmacokinetics to indicators of clinical activity
    • To evaluate the change in the levels of red blood cell (RBC)-specific form of pyruvate kinase (PKR) protein in whole blood
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Have provided signed written informed consent prior to performing any study procedure, including screening procedures.
    2. Be aged 18 years or older.
    3. Have documented clinical laboratory confirmation of PK deficiency, defined as documented presence of at least 2 mutant alleles in the PKLR gene, of which at least 1 is a missense mutation, as determined per the genotyping performed by the study central genotyping laboratory.
    4. Have a history of a minimum of 6 transfusion episodes in the 52-week period prior to date of informed consent as documented in the transfusion history of the subject, which reflects the subject’s typical transfusion burden.
    5. Have complete records of transfusion history, defined as having the following available for the 52 weeks prior to the date of informed consent: (1) all the transfusion dates, (2) the number of blood units transfused for all the transfusions, and (3) Hb concentrations within 1 week prior to transfusion for at least 80% of the transfusions.
    6. Have received at least 0.8 mg oral folic acid daily for at least 21 days prior to the first dose of IMP, to be continued daily during study participation.
    7. Have adequate organ function, as defined by:
    a. Serum AST ≤2.5 × ULN (unless the increased AST is assessed by the Investigator as due to hemolysis and/or hepatic iron deposition) and ALT ≤2.5 × ULN (unless the increased ALT is assessed by the Investigator as due to hepatic iron deposition)
    b. Normal or elevated levels of serum bilirubin. In subjects with serum bilirubin >ULN, the elevation must not be associated with choledocholithiasis, cholecystitis, biliary obstruction, or hepatocellular disease. Elevated bilirubin attributed to hemolysis with or without Gilbert’s syndrome is not exclusionary.
    c. Estimated glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2, measured GFR ≥60 mL/min, or calculated creatinine clearance (CrCL; Cockcroft-Gault) ≥60 mL/min.
    d. Absolute neutrophil count (ANC) ≥1.0 × 109/L
    e. Platelet count ≥100 × 10^9/L, in the absence of a spleen, or platelet count ≥50 × 10^9/L, in the presence of a spleen and in the absence of any other cause of thrombocytopenia.
    f. Activated partial thromboplastin time (aPTT) and international normalized ratio (INR) ≤1.25 × ULN, unless the subject is receiving therapeutic anticoagulants
    8. For women of reproductive potential, have a negative serum pregnancy test during the Screening Period. Women of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion; or who have not been naturally postmenopausal (ie, who have not menstruated at all for at least the preceding 12 months prior to signing informed consent and have an elevated follicle-stimulating hormone (FSH) level indicative of menopause during the Screening Period):
    9. For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of IMP for women and 90 days following the last dose of IMP for men. A highly effective form of contraception is defined as combined (estrogen and progestin containing) hormonal contraceptives (oral, intravaginal, or transdermal) known to be associated with inhibition of ovulation; progestin-only hormonal contraceptives (oral, injectable, or implantable) known to be associated with inhibition of ovulation; intrauterine device; intrauterine hormone releasing system; bilateral tube occlusion; or vasectomized partner. The second form of contraception can include an acceptable barrier method, which includes male or female condoms with or without spermicide, and cervical cap, diaphragm, or sponge with spermicide. Women of reproductive potential using hormonal contraception as a highly effective form of contraception must also utilize an acceptable barrier method while enrolled in the study and for at least 28 days after their last dose of IMP.
    10. Be willing to comply with all study procedures, in particular the Individual TT (calculated based on 52 weeks of transfusion history), for the duration of the study.
    E.4Principal exclusion criteria
    1.Homozygous for R479H mutation or 2 non-missense mutations without presence of another missense mutation in the PKLR gene, as determined per genotyping performed by the study central genotyping lab
    2.Significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data. Such significant medical conditions include not limited to the following:
    a.Poorly controlled hypertension (defined as systolic BP>150mmHg or diastolic BP>90mmHg) refractory to medical management
    b.History of recent (within 6 months prior to informed consent) congestive heart failure; myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke, deep venous thrombosis, or pulmonary or arterial embolism
    c.Cardiac dysrhythmias judged clinically significant by Investigator
    d.Heart-rate corrected QTcF>450msec with exception of subjects with right or left bundle branch block
    e.Clinically symptomatic cholelithiasis or cholecystitis. Prior cholecystectomy is not exclusionary. Subjects with symptomatic cholelithiasis or cholecystitis may be rescreened once disorder treated and clinical symptoms resolved
    f.History of drug-induced cholestatic hepatitis
    g.Iron overload sufficiently severe to result in a clinical diagnosis by the Investigator of cardiac (eg, clinically significant impaired left ventricular ejection fraction), hepatic (eg, fibrosis, cirrhosis), or pancreatic (eg, diabetes) dysfunction
    h.Diagnosis of any other congenital or acquired blood disorder, or any other hemolytic process, except mild allo-immunization, as a consequence of transfusion therapy. Genetic findings that in isolation are predicted to be insufficient to explain the observed clinical phenotype may be allowed (eg, heterozygous status for certain recessive RBC disorders)
    i.Positive test for HBsAg or HCVAb with signs of active hepatitis B or C virus infection. If subject positive for HCVAb, RT-PCR test will be conducted. Subjects with hepatitis C may be re-screened after receiving appropriate hepatitis C treatment
    j.Positive test for HIV-1 or -2 Ab
    k.Active infection requiring the use of parenteral antimicrobial agents or ≥Grade 3 in severity (per NCI CTCAE) within 2 months prior to the first dose of IMP
    l.Diabetes mellitus judged to be under poor control by Investigator or requiring >3 antidiabetic agents, including insulin (all insulins considered 1 agent); use of insulin per se is not exclusionary
    m.History of any primary malignancy with exception of: curatively treated nonmelanomatous skin cancer; curatively treated cervical or breast carcinoma in situ; or other primary tumor treated with curative intent, no known active disease present, and no treatment administered during last 3 years
    n.Unstable extramedullary hematopoiesis that could pose a risk of imminent neurologic compromise
    o.Current/recent history of psychiatric disorder that, in opinion of Investigator/Medical Monitor (or designee), could compromise ability of subject to cooperate with study visits and procedures
    3.History of transfusions occurring on average more frequently than once every 3 weeks during the 52 weeks prior to signing ICF
    4.Splenectomy scheduled during the study drug period or have undergone splenectomy within 12 months prior to signing ICF
    5.Currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo. Prior/subsequent participation in the PK Deficiency NHS or PK Deficiency Registry is permitted however concurrent participation is not; subjects enrolling in current study will be expected to temporarily suspend participation in NHS or Registry
    6.Exposure to any investigational drug, device, or procedure within 3 months prior to the first dose of IMP
    7.Prior bone marrow or stem cell transplant
    8.Currently pregnant or breastfeeding
    9.History of major surgery within 6 months of signing ICF. Note that procedures such as laparoscopic gallbladder surgery are not considered major in this context
    10.Currently receiving medications that are strong inhibitors of CYP3A4, strong inducers of CYP3A4, strong inhibitors of P-gp, or digoxin that haven’t stopped for at least 5 days or a timeframe equivalent to 5 half-lives (whichever longer) prior to first dose of IMP
    11.Currently receiving hematopoietic stimulating agents (eg, EPOs, granulocyte colony stimulating factors, thrombopoietins) that have not been stopped for a duration of at least 28 days prior to first dose of IMP
    12.History of allergy to sulfonamides if characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis, or other serious clinical manifestations
    13.History of allergy to AG-348 or excipients
    14.Currently receiving anabolic steroids including testosterone preparations within 28 days prior to the first dose of IMP
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is the proportion of subjects who achieve a reduction in transfusion burden, defined as a ≥33% reduction in the number of RBC units transfused during the 24 weeks of Part 2 compared with the historical transfusion burden standardized to 24 weeks (Standardized Control Period).
    E.5.1.1Timepoint(s) of evaluation of this end point
    All through the study: for each transfusion administered at any time during the study, the date of transfusion, number of RBC units transfused, HCT, and volume of RBC units will be recorded.
    E.5.2Secondary end point(s)
    Secondary Endpoints
    The secondary endpoints of the study are the following:
    • Annualized total number of RBC units transfused during the study (both Part 1 and Part 2) compared with the historical transfusion burden
    • Number of transfusion episodes during Part 2 compared with the Standardized Control Period
    • Proportion of subjects who become transfusion-free, defined as 0 transfusions administered during Part 2
    • Proportion of subjects who achieve Hb concentrations in the normal range at least once, 8 weeks or more after a transfusion in Part 2
    • Safety endpoints, including the type, incidence, severity, and relationship to treatment of adverse events (AEs) and serious adverse events (SAEs) and AEs leading to treatment dose reduction, treatment interruption, and treatment discontinuation
    • Laboratory tests over time (eg. serum chemistry/liver function tests/[LFTs], coagulation, lipids, sex steroids, urinalysis), physical examination findings, dual energy X-ray absorptiometry (DXA) scans (hip and lumbar spine), vital signs, and 12-lead electrocardiograms (ECG) data

    Exploratory Endpoints
    The exploratory endpoints of the study are the following:
    • Change from baseline in the following markers of hemolysis: bilirubin, lactate dehydrogenase (LDH), and haptoglobin levels
    • Change from baseline in markers of erythropoietic activity
    • Change from baseline in markers of iron and indicators of iron overload
    • Change from baseline over time in HRQoL scores (ie, Pyruvate Kinase Deficiency Impact Assessment [PKDIA], Pyruvate Kinase Deficiency Diary [PKDD], EuroQol-5D-5L [EQ-5D-5L])
    • Characterization of pharmacokinetic profile (drug concentrations over time) and determination of pharmacokinetic parameters of AG-348 (eg, area under the plasma concentration × time curve [AUC], maximum [peak] concentration [Cmax], and others as applicable) in Part 2
    • Exposure-response (or pharmacokinetic-pharmacodynamic) relationship between relevant
    pharmacokinetic parameters and endpoints that are indicators of clinical activity
    • Changes in total PKR protein levels
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary:
    Transfusion & AE: all through the study
    Physical exa: Scr, part 1 d1, wk12, part 2 d1, wk12, 24 + FU (ED)
    Vital sign, Hematology, Liver function: all visits
    ECG: Scr, part 1 d1, part 2 d1, FU
    DXA scan: Scr, part 2 d1, wk24, FU (ED)
    Serum chem.: Scr, part 1 d1, wk12, part 2 d1, wk12, 24, FU
    Coagulation & Urinalysis: Scr, part 1 d1, wk12, part 2 d1, wk12, 24, FU
    Lipid: part 1 d1, wk6, 12, part 2 d1, wk4, 8, 12, 18, 24, FU
    Sex steroids: part 1 d1, wk4, 8, 12, part 2 d1, wk4, 8, 12, 18, 24, FU

    Exploratory:
    MRI: Scr, part 2 d1, wk24, FU (ED)
    Iron panel: Scr, part 1 d1, wk12, part 2 d1, wk24, FU (ED)
    HRQoL assess.: Scr, part 1 d1, wk4, 8, 12, part 2 d1, wk 4, 8, 12, 18, 24, FU
    PK profile: part 2 wk 24
    PKR prot.: Scr, part 1 d1, part 2 wk 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 Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Part 1 individualized dose optimization followed by a part 2 fixed-dose period
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    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
    Canada
    Czech Republic
    Denmark
    France
    Ireland
    Italy
    Netherlands
    Spain
    Switzerland
    Thailand
    Turkey
    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 months9
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days25
    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: 40
    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 state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 28
    F.4.2.2In the whole clinical trial 40
    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)
    Subjects who complete the study through Week 24 of Part 2 may be eligible to enter in an extension study, should one be offered.
    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 Decision2018-02-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-11-12
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA