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   42771   clinical trials with a EudraCT protocol, of which   7044   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) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:2020-005548-48
    Sponsor's Protocol Code Number:TVB009-IMB-30085
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-03-18
    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 ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2020-005548-48
    A.3Full title of the trial
    A Randomized, Double-Blind, Multinational, Multicenter Study to Compare Efficacy, Safety, and Immunogenicity of TVB-009P and Denosumab (PROLIA®) in Patients with Postmenopausal Osteoporosis
    Randomizované, dvojito zaslepené, medzinárodné, multicentrické klinické skúšanie na porovnanie účinnosti, bezpečnosti a imunogenicity TVB-009P a denosumabu (PROLIA®) u pacientok s postmenopauzálnou osteoporózou
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis
    A.4.1Sponsor's protocol code numberTVB009-IMB-30085
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04729621
    A.5.4Other Identifiers
    Name:IND numberNumber:137313
    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 SponsorTeva Branded Pharmaceutical Products R&D, 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 supportTeva Branded Pharmaceutical Products R&D, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSanaClis s.r.o.
    B.5.2Functional name of contact pointClinical Trials Department
    B.5.3 Address:
    B.5.3.1Street AddressStaré Grunty 130
    B.5.3.2Town/ cityBratislava
    B.5.3.3Post code84104
    B.5.3.4CountrySlovakia
    B.5.4Telephone number+421917 607 952
    B.5.5Fax number+421264287 625
    B.5.6E-mailinfo@sanaclis.eu
    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 nameTVB-009 (denosumab) solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS) (TVB-009P)
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    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 INNDenosumab
    D.3.9.1CAS number 615258-40-7
    D.3.9.2Current sponsor codeTVB-009
    D.3.9.3Other descriptive nameDENOSUMAB
    D.3.9.4EV Substance CodeSUB29173
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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 Yes
    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 Yes
    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 RoleComparator
    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 namePROLIA United States (US) (denosumab) solution for injection 60 mg/mL (1 mL) PFS
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    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 INNDenosumab
    D.3.9.1CAS number 615258-40-7
    D.3.9.3Other descriptive nameDENOSUMAB
    D.3.9.4EV Substance CodeSUB29173
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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 Yes
    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 Yes
    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
    Postmenopausal Osteoporosis
    Postmenopauzálna osteoporóza
    E.1.1.1Medical condition in easily understood language
    Postmenopausal Bone thinning
    Rednutie kostí po menopauze
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10031285
    E.1.2Term Osteoporosis postmenopausal
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to demonstrate that there are no clinically meaningful differences in efficacy between TVB-009P and PROLIA US administered
    subcutaneously in patients with postmenopausal osteoporosis.
    Primárnym cieľom tohto klinického skúšania je preukázať, že u pacientok s postmenopauzálnou osteoporózou nevyskytli sa klinicky významné rozdiely v účinnosti medzi liekmi TVB-009P a PROLIA US, podávaných subkutánne.
    E.2.2Secondary objectives of the trial
    A secondary objective is to compare:
    - further efficacy and pharmacodynamic parameters between TVB-009P and PROLIA US.
    - efficacy and pharmacodynamic parameters between TVB-009P and PROLIA US after a single transition from PROLIA US to TVB-009P.
    - the safety and tolerability, including device-related events, between TVB-009P and PROLIA US throughout the study.
    - the safety and tolerability between TVB-009P and PROLIA US after a single transition from PROLIA US to TVB-009P, including device-related events.
    A secondary objective of this study is to assess the immunogenicity of TVB-009P:
    - in comparison with PROLIA US throughout the study.
    - in comparison with PROLIA US after a single transition from PROLIA US to TVB-009P.
    Sekundárnym cieľom klinického skúšania je:
    - porovnanie ďalšej účinnosti a farmakodynamických parametrov medzi liekmi TVB-009P a PROLIA US.
    - porovnanie účinnosti a farmakodynamických parametrov medzi liekmi TVB-009P a PROLIA US po jednom prechode z PROLIA US na TVB-009P.
    - porovnanie bezpečnosti a znášanlivosti, vrátane udalostí súvisiacich s pomôckou, medzi liekmi TVB-009P a PROLIA US počas celého klinického skúšania.
    - porovnať bezpečnosť a znášanlivosť medzi liekmi TVB-009P a PROLIA US po jednom prechode z PROLIA US na TVB-009P, vrátane udalostí súvisiacich s pomôckou.
    - vyhodnotiť imunogenicitu TVB-009P v porovnaní s PROLIA US počas celého skúšania.
    - vyhodnotiť imunogenicitu TVB-009P v porovnaní s PROLIA US po jednom prechode z PROLIA US na TVB-009P.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients may be included in this study only if they meet all of the following criteria:
    a. The patient provides a signed and dated written informed consent.
    b. The patient is a clinically stable, ambulatory, female postmenopausal adult (≥60 and ≤90 years) with a diagnosis of osteoporosis.
    c. The patient is of postmenopausal status, defined as: Spontaneous amenorrhea for >12 months, or Spontaneous amenorrhea >6 months and serum follicle stimulating hormone
    (FSH) and estradiol (E2) in menopausal range, or
    Surgical menopause at least 6 weeks before the start of screening.
    d. The patient has a body weight ≥50 kg and ≤90 kg (≥110 lb and ≤198 lb) at screening.
    e. The patient agrees to be supplemented with 1000 mg calcium and at least 400 IU vitamin D daily from screening until the last visit.
    f. The patient has a BMD-measurement T-score of less than -2.5 but not less than -4.0 by dual energy X-ray absorptiometry (DXA) at the lumbar spine at screening based on central reader assessment.
    g. The patient has at least three (3) vertebrae in the L1-L4 region that are evaluable by DXA.
    h. The patient has serum 25 (OH) vitamin D level >20 ng/mL at screening and no current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory. Vitamin D and calcium supplements will be provided and patients may be rescreened once to re-evaluate calcium and/or vitamin D level post repletion.
    i. The patient must be willing and able to comply with study restrictions and to remain
    at the investigational center for the required duration during the study period, and willing to return to the investigational center for further visits, as applicable, and the follow-up procedures and assessments as specified in this protocol.
    Kritériá zaraďovania: Pacientky môžu byť zaradené do tohto klinického skúšania, iba ak spĺňajú všetky nasledujúce kritériá:
    a. Pacientka poskytne podpísaný a datovaný písomný informovaný súhlas.
    b. Pacientka je klinicky stabilná, ambulantný pacient, postmenopauzálna dospelá žena (≥ 60 a ≤ 90 rokov) s diagnózou osteoporózy.
    c. Pacientka je v postmenopauzálnom stave, ktorý je definovaný ako:
    - spontánna amenorea viac ako 12 mesiacov, alebo
    - spontánna amenorea viac ako 6 mesiacov a sérom hormónu stimulujúceho folikuly (FSH) a estradiolu (E2) v menopauzálnom rozmedzí, alebo chirurgická menopauza minimálne 6 týždňov pred začiatkom skríningu.
    d. Pacientka má pri skríningu telesnú hmotnosť ≥ 50 kg a ≤ 90 kg (≥ 110 lb a ≤ 198 lb).
    e. Pacientka súhlasí, že bude od skríningu do poslednej kontroly užívať 1 000 mg vápnika a najmenej 400 IU vitamínu D denne.
    f. Pacientka má T-skóre merania kostnej minerálnej hustoty (BMD) menej ako -2,5, ale nie menej ako -4,0 podľa dvojenergetickej RTG absorpciometrie (DXA) v bedrovej chrbtici pri skríningu na základe hodnotenia centrálného čitateľa.
    g. Pacientka má minimálne 3 (tri) stavce v oblasti L1-L4, ktoré je možné vyhodnotiť pomocou DXA.
    h. Pacientka má na skríningu hladinu 25 (OH) vitamínu D v sére > 20 ng/ml a aktuálne nemá žiadnu hyper- alebo hypokalcémiu, ktorá je definovaná ako koncentrácia vápnika v sére korigovaná vzhľadom na albumín mimo normálneho rozsahu podľa hodnotenia centrálneho laboratória. Pacientky dostanú štandardnú liečbu s obsahom vitamínu D a vápnika a môžu podstúpiť re-skríning s cieľom prehodnotenia hladiny vápnika a/alebo vitamínu D po doplnení.
    i. Pacientka musí byť ochotná a schopná vyhovieť obmedzeniam klinického skúšania a zostať na pracovisku klinického skúšania, počas požadovaného obdobia trvania skúšania a musí byť ochotná vrátiť sa na pracovisko klinického skúšania podľa potreby a na ďalšie prípadné kontroly a následné zákroky tak ako sa to uvádza v tomto protokole.
    E.4Principal exclusion criteria
    Patients will be excluded from participating in this study if they meet any of the following
    criteria:
    a. The patient has a known malabsorption of calcium or vitamin D supplements.
    b. The patient has a metabolic or bone disease (except osteoporosis) such as Paget’s disease, Cushing’s disease, rheumatoid arthritis, sclerosteosis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, hyperprolactinemia, malabsorption syndrome, osteomyelitis, multiple myeloma or related lymphoproliferative disorder, or bone metastases.
    c. The patient has a current, uncontrolled hyperthyroidism or hypothyroidism, per
    patient report or chart review.
    d. The patient has hypoparathyroidism or hyperparathyroidism (irrespective of current
    controlled or uncontrolled status).
    e. The patient has a history and/or presence of risk factors of osteonecrosis of the jaw, as
    determined by the principal investigator, (eg, unhealed open soft tissue lesions in the mouth, poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, recent or planned invasive dental procedures such as tooth extractions within the next 18 months), presence of anemia or coagulopathy at screening, and/or inability to maintain oral hygiene during the study.
    f. The patient has a history and/or presence of 1 severe or more than 2 moderate vertebral fractures (as determined by central reading of lateral spine X-ray during the screening period).
    g. The patient has a history and/or presence of hip fracture or atypical femur fracture.
    h. The patient has participated in another study of an IMP (or a medical device) within
    the previous 30 days or 5 half-lives of the IMP (whichever is longer) or longer if required by local regulations, or is currently participating in another study of an IMP (or a medical device).
    i. The patient has a known hypersensitivity to any components of the IMPs stated in this
    protocol or to calcium or vitamin D.
    j. The patient has a renal impairment manifested with an estimated glomerular filtration rate (eGFR) <45 mL/min.
    k. The patient has cardiac disease as per investigator's discretion, including electrocardiogram (ECG) abnormalities at screening indicating significant risk of safety for patients participating in the study.
    l. The patient has a malignancy or past malignancy (except for local non-melanoma
    skin cancer fully resected).
    m. The patient has a current skin infection(s).
    n. The patient has infectious disease:
    - Acute infection and/or antibiotic treatment must be resolved 28 days prior to the first dose of IMP.
    - Any relevant chronic infection. Ongoing hepatitis B, hepatitis C, human immunodeficiency virus (HIV) Types 1 or 2 infection.
    - Positive test for coronavirus disease 2019 (COVID-19) during screening or patient reporting a recent history of confirmed COVID-19 which had not fully recovered more than 14 days before screening.
    o. The patient has any medical condition that (treated or untreated), in the opinion of the
    investigator, could jeopardize or would compromise the patient’s safety or ability to
    participate in this study.
    p. The patient has had any prior treatment with denosumab (PROLIA or XGEVA or biosimilars of denosumab products).
    q. The patient has used intravenous bisphosphonates within less than 5 years prior to screening.
    r. The patient has used oral bisphosphonates within the 12 months prior to start of screening and/or cumulative use >3 years before the start of screening.
    s. The patient has ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements). The following rules for prior use of osteoporosis treatments
    have to be adhered to:
    - Drugs being investigated for osteoporosis, eg romosozumab: dose received at any time.
    - Strontium or fluoride (for osteoporosis): dose received at any time.
    - Teriparatide or any parathyroid hormone (PTH) analogs: dose received within 12 months before the start of screening.
    - Calcitonin: dose received within 6 months before the start of screening.
    - Cinacalcet: dose received within 3 months before the start of screening.
    t. The patient has ongoing use of any bone active drugs which can affect BMD including:
    - Heparin (except topical), anti-convulsives (with the exception of benzodiazepines), systemic ketoconazole, adrenocorticotropic hormone, lithium, gonadotropin releasing hormone agonists, or anabolic steroids; dose received within 3 months before the start of screening.
    - Systemic glucocorticosteroids: total cumulative dose of ≥50 mg within 3 months
    prior to randomization.
    - Systemic oral or transdermal estrogen, or selective estrogen receptor modulators:
    more than 1 month of cumulative use within 6 months prior to randomization.
    v. The patient has a history of chronic alcohol or drug abuse within the previous 6 months.
    w. The patient is vulnerable (eg, people kept in detention).
    Kritériá vyraďovania: Pacientky budú vylúčené z účasti v tomto klinickom skúšaní, ak sa u nich objaví niektoré z nasledujúcich kritérií:
    a. Pacientka má známu malabsorpciu doplnkov vápnika alebo vitamínu D.
    b. Pacientka má metabolické alebo kostné ochorenie (popri osteoporóze), ako je Pagetova choroba, Cushingova choroba, reumatoidná artritída, sklerosteóza, osteomalácia, osteogenesis imperfecta, osteopetróza, ankylozujúca spondylitída, hyperprolaktinémia, malabsorpčný syndróm, osteomyelitída, mnohopočetný myelóm, alebo súvisiaca lymfoproliferatívna porucha, prípadne kostné metastázy.
    c. Pacientka aktuálne trpí nekontrolovanou hypertyreózou alebo hypotyreózou podľa lekárskej správy pacientky alebo na základe preskúmania lekárskej dokumentácie.
    d. Pacientka trpí hypoparatyreoidizmom alebo hyperparatyroidizmom (bez ohľadu na aktuálny kontrolovaný alebo nekontrolovaný stav).
    e. Pacientka má v anamnéze alebo sa u pacientky vyskytujú rizikové faktory osteonekrózy čeľuste na základe určenia hlavným skúšajúcim (napr. nezahojené otvorené lézie mäkkých tkanív v ústach, nesprávna ústna hygiena, periodontálne ochorenie, zle nasadené zubné náhrady, zubné ochorenie, nedávne alebo plánované invazívne zubné zákroky, napríklad extrakcia zubov v priebehu nasledujúcich 18 mesiacov), pacientka trpí anémiou alebo koagulopatiou pri skríningu a/alebo nie je schopná dodržiavať ústnu hygienu počas klinického skúšania.
    f. Pacientka v minulosti prekonala 1 závažnú alebo viac ako 2 stredne závažné zlomeniny stavcov (podľa centrálneho RTG nálezu pri snímaní laterálnej chrbtice počas skríningového obdobia) a/alebo ide o aktuálny stav pacientky.
    g. Pacientka má v anamnéze alebo sa u nej vyskytujú zlomeniny bedrového kĺbu alebo atypické zlomeniny stehennej kosti.
    h. Pacientka sa zúčastnila v inom klinickom skúšaní skúšaného lieku (IMP) (alebo zdravotníckej pomôcky) za posledných 30 dní alebo 5 polčasov rozpadu IMP (podľa toho, čo je dlhšie), alebo dlhšie ak si to úrady a miestne predpisy vyžadujú, alebo sa momentálne zúčastňuje v inom klinickom skúšaní IMP (alebo zdravotníckej pomôcky).
    i. U pacientky je známa precitlivenosť na ktorúkoľvek zložku skúšaného lieku uvedenú v tomto protokole alebo na vápnik alebo vitamín D.
    j. Pacientka má poruchu funkcie obličiek prejavujúcu sa odhadovanou rýchlosťou glomerulárnej filtrácie (eGFR) < 45 ml/min.
    k. Pacientka trpí srdcovým ochorením podľa uváženia skúšajúceho, vrátane abnormalít elektrokardiogramu (EKG) pri skríningu, ktoré naznačujú významné bezpečnostné riziko pre pacientky zúčastňujúce sa v skúšaní.
    l. Pacientka má malignitu alebo mala malignitu v minulosti (s výnimkou lokálneho nemelanómového karcinómu kože, ktorý bol úplne resekovaný).
    m. Pacientka aktuálne trpí infekciou kože.
    n. Pacientka trpí infekčným ochorením:
    - Akútna infekcia a/alebo liečba antibiotikami sa musí vyriešiť 28 dní pred prvou dávkou IMP.
    - Akákoľvek relevantná chronická infekcia.
    - Prebiehajúca infekcia hepatitídou B, hepatitídou C, vírusom ľudskej imunodeficiencie (HIV) typu 1 alebo 2.
    - Pozitívny test na koronavírusové ochorenie 2019 (COVID-19) počas skríningu alebo výkaz nedávnej anamnézy pacientky s potvrdeným ochorením COVID-19, ktorá sa úplne nezotavila, viac ako 14 dní pred skríningom.
    p. Pacientka už bola liečená denosumabom (PROLIA alebo XGEVA alebo biologicky podobnými liekmi s denosumabom).
    q. Pacientka používala intravenózne bisfosfonáty v období menej ako 5 rokov pred skríningom.
    r. Pacientka používala perorálne bisfosfonáty v období 12 mesiacov pred začiatkom skríningu a/alebo ich používala kumulatívne > 3 roky pred začiatkom skríningu.
    s. Pacientka v súčasnosti absolvuje akúkoľvek liečbu osteoporózy (inú ako doplnkami vápnika a vitamínu D). Nasledujúce pravidlá je potrebné dodržiavať v prípade predchádzajúcej liečby osteoporózy nasledovne:
    - Skúšané lieky na osteoporózu, napr. romosozumab: dávku, ktorú ste dostali kedykoľvek.
    - Stroncium alebo fluorid (na osteoporózu): dávka, ktorá bola podaná kedykoľvek.
    - Teriparatid alebo akékoľvek analógy paratyroidného hormónu (PTH): dávka, ktorá bola podaná do 12 mesiacov pred začiatkom skríningu.
    - Kalcitonín: dávka, ktorá bola podaná v období 6 mesiacov pred začiatkom skríningu.
    - Cinakalcet: dávka, ktorá bola podaná v období 3 mesiacov pred začiatkom skríningu.
    t. Pacientka neustále užíva lieky na aktiváciu kosti, ktoré môžu mať vplyv na BMD, napr.:
    - heparín (okrem topického), antikonvulzíva (s výnimkou benzodiazepínov), systémový ketokonazol, adrenokortikotropný hormón, lítium, agonisty hormónu uvoľňujúceho gonadotropín alebo anabolické steroidy, dávka podaná v období 3 mesiacov pred začiatkom skríningu.
    - Systémové glukokortikosteroidy: celková kumulatívna dávka ≥ 50 mg v období 3 mesiacov pred randomizáciou.
    - Systémové orálne alebo transdermálne modulátory estrogénu alebo selektívne modulátory estrogénových receptorov: V období 6 mesiacov pred randomizáciou nesmie byť viac ako 1 mesiac kumulatívneho užívania.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is:
    - the percent change from baseline in lumbar spine-bone mineral density (LS-BMD) at week 52 based on centrally assessed dual-energy X-ray absorptiometry (DXA) measurements
    - The co-primary efficacy endpoint for the European Union (EU) submission is the percent change from baseline in serum C-telopeptide cross-link of type 1 collagen (sCTX-1) at week 26. For the EU submission, this endpoint is regarded as co-primary. For the United States (US) submission, this endpoint is regarded as secondary
    Primárny koncový ukazovateľ účinnosti je
    • percentuálna zmena od východiskovej hodnoty v minerálnej hustote kostí bedrovej chrbtice (LS-BMD) po 52. týždeň na základe centrálne vyhodnotených meraní dvojenergetickej röntgenovej absorpciometrie (DXA).
    • Ko-primárny koncový ukazovateľ účinnosti pre účely podania žiadosti v Európskej únii (EÚ) je percentuálna zmena zosieťovania C-telopeptidu kolagénu 1. typu v sére (sCTX-1) od východiskovej hodnoty po hodnotu v 26. týždni. Pri podaní žiadosti EÚ sa tento koncový ukazovateľ považuje za ko-primárny. V prípade podania žiadosti v Spojených štátoch (USA) sa tento koncový ukazovateľ považuje za sekundárny.
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 26 and week 52
    Týždeň 26 a 52
    E.5.2Secondary end point(s)
    The secondary efficacy and pharmacodynamic endpoints are:
    - percent change from baseline in LS-BMD at week 26 based on centrally assessed DXA measurements
    - percent change from baseline in femoral neck bone mineral density (BMD) by DXA at week 26 and at week 52
    - percent change from baseline in total hip BMD by DXA at week 26 and at week 52
    - percent change from baseline in sCTX-1 at all time points
    - sCTX-1 suppression at week 4
    - percent change from baseline in procollagen type 1 N propeptide (P1NP) at week 26 and week 52
    - incidence of fractures up to week 52
    The pharmacodynamic/efficacy endpoints in the transition period are:
    - percent change from week 52 in LS-BMD by DXA at week 78
    - difference between percent change from baseline in sCTX-1 between week 52 and week 78
    - percent change from week 52 in femoral neck BMD by DXA at week 78
    - percent change from week 52 in total hip BMD by DXA at week 78
    - difference between percent change from baseline in P1NP between week 52 and week 78
    - incidence of fractures up to week 78
    The safety and tolerability endpoints are:
    - adverse events (and the number of patients who withdraw from the study due to adverse events)
    - vital signs
    - laboratory tests (hematology, serum chemistry, and urinalysis)
    - electrocardiogram (ECG)
    - local tolerability at injection site
    - use of concomitant medications
    - device-related adverse events and malfunctions
    The immunogenicity endpoint is:
    - incidence of patients with confirmed positive anti-drug antibody (ADA) sample
    For confirmed positive samples, the ADA titer and the neutralizing potential will be tested.
    The effect of positive immunogenicity findings on pharmacokinetics, efficacy, and safety will be assessed if applicable.
    Sekundárne parametre účinnosti a farmakodynamické parametre sú:
    • percentuálna zmena od východiskovej hodnoty v LS-BMD po hodnotu v 26. týždni na základe centrálne vyhodnotených meraní DXA.
    • percentuálna zmena od východiskovej hodnoty minerálnej hustoty kosti krčka stehennej kosti (BMD) pomocou DXA po hodnotu v 26. týždni a v 52. týždni.
    • percentuálna zmena od východiskovej hodnote celkovej BMD bedrového kĺbu pomocou DXA po hodnotu v 26. týždni a v 52. týždni.
    • percentuálna zmena od východiskovej hodnote v sCTX-1 vo všetkých časových bodoch.
    • supresia sCTX-1 v 4. týždni.
    • percentuálna zmena od východiskovej hodnote propeptidu prokolagénu typu 1 N (P1NP) v 26. týždni a 52. týždni.
    • výskyt zlomenín do 52. týždňa.
    Koncové ukazovatele farmakodynamiky/účinnosti v prechodnom období sú:
    • percentuálna zmena od 52. týždňa v LS-BMD až po DXA v 78. týždni.
    • rozdiel medzi percentuálnou zmenou oproti východiskovej hodnote v sCTX-1 medzi 52. týždňom a 78. týždňom.
    • percentuálna zmena od 52. týždňa v BMD krčka stehennej kosti pomocou DXA v 78. týždňa.
    • percentuálna zmena od 52. týždňa v BMD bedrového kĺbu pomocou DXA do 78. týždňa.
    • rozdiel medzi percentuálnou zmenou oproti východiskovej hodnote v P1NP medzi 52. týždňom a 78. týždňom.
    • výskyt zlomenín do 78. týždňa.
    Koncové ukazovatele bezpečnosti a znášanlivosti sú:
    • nežiaduce udalosti (a počet pacientok, ktorí odstúpia od skúšania z dôvodu nežiaducich udalostí).
    • životné funkcie.
    • laboratórne testy (hematológia, sérologické vyšetrenie a analýza moču).
    • elektrokardiogram (EKG).
    • lokálna znášanlivosť v mieste vpichu.
    • užívanie konkomitantných liekov.
    • nežiaduce udalosti a poruchy súvisiace s pomôckou.
    Koncovým ukazovateľom imunogenicity je:
    • výskyt pacientok s potvrdenou pozitívnou vzorkou protiliekových protilátok (ADA).
    U potvrdených pozitívnych vzoriek sa bude testovať titer ADA a neutralizačný potenciál.
    V prípade potreby sa vyhodnotí vplyv pozitívnych nálezov imunogenicity na farmakokinetiku, účinnosť a bezpečnosť.

    E.5.2.1Timepoint(s) of evaluation of this end point
    week 26, 52 and 78
    Týždeň 26, 52 a 78
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    immunogenecity
    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 No
    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) Yes
    E.8.2.2Placebo No
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA34
    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
    Bulgaria
    Czechia
    Georgia
    Germany
    Hungary
    Poland
    Russian Federation
    Slovakia
    Ukraine
    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
    LPLV
    LPLV
    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 months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    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: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 261
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 171
    F.4.2.2In the whole clinical trial 326
    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 Decision2021-07-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-04-09
    P. End of Trial
    P.End of Trial StatusOngoing
    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