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    Summary
    EudraCT Number:2017-001944-36
    Sponsor's Protocol Code Number:20170149
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-10-24
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2017-001944-36
    A.3Full title of the trial
    A Phase 1b/2a Study to Evaluate the Safety and Efficacy of AMG 592 in Subjects with Active Rheumatoid Arthritis With Inadequate Response to Standard of Care Therapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Efficacy of AMG 592 in Subjects with Active Rheumatoid Arthritis
    A.4.1Sponsor's protocol code number20170149
    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 SponsorAmgen 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 supportAmgen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen Bulgaria EOOD
    B.5.2Functional name of contact pointMedical department
    B.5.3 Address:
    B.5.3.1Street AddressManastirski Livadi West, 63 Kazbek Str., Viridian Officess
    B.5.3.2Town/ citySofia
    B.5.3.3Post code1680
    B.5.3.4CountryBulgaria
    B.5.4Telephone number+35924247440
    B.5.6E-maileu-bg-medinfo@amgen.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 nameAMG592
    D.3.4Pharmaceutical form 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 INNN/A
    D.3.9.2Current sponsor codeAMG 592
    D.3.9.3Other descriptive nameRECOMBINANT FACTOR FC FUSION PROTEIN
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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
    Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    Rheumatoid Arthritis
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10039075
    E.1.2Term Rheumatoid arthritis and associated conditions
    E.1.2System Organ Class 100000004870
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 1b
    • To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of AMG 592 in subjects with active RA
    Phase 2a
    • To evaluate the efficacy of AMG 592 at week 12 as measured by the American
    College of Rheumatology 20% improvement criteria (ACR 20) in adult subjects with moderate to severe RA
    E.2.2Secondary objectives of the trial
    Phase 1b
    • To characterize the pharmacokinetic (PK) profile following treatment with AMG 592
    • To evaluate the incidence of anti-AMG 592 antibody formation and cross-reactivity to human IL-2.
    Phase 2a
    • To evaluate the effect of treatment with AMG 592 on other measures of disease
    • To evaluate the safety of AMG 592
    • To characterize the PK of AMG 592 in subjects with RA activity at week 12
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Subject has provided informed consent prior to initiation of any study specific
    activities/procedures.
    - Age ≥ 18 to ≤ 70 years of age at screening
    - A diagnosis of RA consistent with the 1987 or 2010 American College of
    Rheumatology (ACR)/European League Against Rheumatism classification
    criteria
    - Active RA defined as:
    • Phase 1b: DAS-28-CRP > 2.6 at screening. The 28-joint count consists of
    the finger joints excluding the distal interphalangeal joints, the wrists, elbows,
    shoulders, and knees.
    • Phase 2a: ≥ 6 swollen joints (based on 66-joint count) and ≥ 6 tender joints
    (based on 68-joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility. Additionally, C-reactive protein (CRP) must be greater than the upper limit of normal (ULN) per the central laboratory at screening.
    - Receiving treatment with methotrexate for ≥ 12 weeks and on a stable dose
    ≥ 15 mg weekly for ≥ 8 weeks prior to day 1. A lower methotrexate dose is
    acceptable (but no lower than 10 mg weekly) if it is the highest tolerated dose
    and gastrointestinal or hematologic toxicity at doses ≥ 15 mg weekly is
    documented by the investigator.
    - Receiving treatment with folic or folinic acid per investigator judgment or
    according to local standard of care.
    - Phase 1b only: Subject may be receiving a stable dose of leflunomide,
    sulfasalazine, hydroxychloroquine, minocycline in combination with methotrexate and the dose must be stable for ≥ 8 weeks prior to day 1.
    - Subject may be receiving a stable dose of prednisone ≤ 10mg daily or other
    equivalent corticosteroid dose and the dose must be stable for ≥ 2 weeks prior to
    day 1.
    - Phase 1b only. Normal or clinically acceptable ECG values (12-lead reporting
    ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline
    based on opinion of the investigator.
    - Immunizations (tetanus, diphtheria, pertussis, seasonal influenza [during flu
    season], and pneumococcal [polysaccharide] vaccinations) up to date per local
    standards as determined by the investigator.
    E.4Principal exclusion criteria
    Disease Related:
    - Class IV RA according to ACR revised response criteria
    - Diagnosis of Felty’s Syndrome (RA, splenomegaly and granulocytopenia)
    Other Medical Conditions
    - Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening.
    - Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1.
    - Known history of active tuberculosis
    - Positive test for tuberculosis during screening
    - Positive for hepatitis B surface antigen, hepatitis B core antibody .
    - Phase 1b only: Positive for Human Immunodeficiency Virus (HIV) at screening or
    known to be HIV positive. Phase 2a only: Known history of HIV
    - Positive drug or alcohol urine test at screening.
    - Presence of one or more significant concurrent medical conditions per
    investigator judgment, including but not limited to the following:
    • poorly controlled diabetes or hypertension
    • chronic kidney disease stage IIIb, IV, or V
    • symptomatic heart failure (New York Heart Association class II, III, or IV)
    • myocardial infarction or unstable angina pectoris within the past
    12 months prior to randomization
    • severe chronic pulmonary disease (eg, requiring oxygen therapy)
    • multiple sclerosis or any other demyelinating disease
    • major chronic inflammatory disease or connective tissue disease other
    than RA
    - Malignancy except non-melanoma skin cancers, cervical or breast ductal
    carcinoma in situ within the last 5 years.
    - History of alcohol or substance abuse within 6 months of screening
    - Phase 1b only: Current smoker, and/or use of any nicotine or tobacco containing products within the last 6 months prior to day 1.
    - Phase 1b only: Subject unwilling to limit alcohol consumption
    Subjects who have received intra-articular or systemic corticosteroid injections
    for treatment of acute RA flare (not being part of a regular therapeutic regimen)
    within 4 weeks prior to screening.
    - Currently receiving or had treatment with cyclophosphamide, chlorambucil,
    nitrogen mustard, or any other alkylating agent ≤ 6 months prior to day 1.
    - Prior treatment with more than a total of 3 therapies that include biologic
    DMARDs or oral synthetic DMARDs (such as tofacinitib, baricitinib). Prior
    treatment consists of at least 4 doses of a given therapy where the doses
    were given solely for treatment of RA disease. Prior therapies must not
    have been used within the following time periods:
     ≤ 4 weeks prior to day 1 for etanercept and anakinra
     ≤ 6 months for rituximab
     ≤ 2 weeks for oral janus kinase inhibitors
     ≤ 9 weeks prior to day 1 for all therapies not listed above
    - Currently receiving or had treatment with any of the following ≤ 12 weeks prior to day 1:
    • azathioprine
    • cyclosporine
    • gold
    • mycophenolate mofetil
    • Prosorba column
    • Tacrolimus
    - Phase 2a only: Currently receiving or had treatment with leflunomide ≤ 12 weeks prior to day 1 unless an active washout with cholestyramine has been performed.
    - Phase 2a only: Currently receiving or had treatment with any of the following
    ≤ 4 weeks prior to day 1:
    • hydroxychloroquine
    • sulfasalazine
    • minocycline
    • oral janus kinase inhibitor (eg, tofacitinib, baricitinib)
    • intra-articular, intramuscular or intravenous corticosteroids, including
    adrenocorticotropic hormone
    • intra-articular hyaluronic acid injections
    • live vaccines
    - For Phase 2 only: Unstable dose of non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, and/or analgesics which is taken on an unscheduled basis and/or initiated <4 weeks prior to day 1.
    - Received the following within 12 hours prior to screening or day 1:
    acetaminophen, NSAIDs, tramadol, and/or any narcotic analgesics such as but
    not limited to hydrocodone, codeine, tramadol, propoxyphene and/or oxycodone. Subject has taken oxycontin within 24 hours prior to screening or day 1.
    - Phase 1b only: Received any herbal medicines (eg, St John’s wort), or
    non-vitamin dietary supplements (eg, magnesium) with the exception of
    calcium within 4 weeks prior to day 1.
    - Phase 1b only: Positive drug or alcohol urine test for illicit drugs at screening. Prescription medications detected by the drug test are allowed if they are being taken under the direction of a physician.
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1b
    • Treatment-emergent adverse events.
    • Clinically significant changes in vital signs, laboratory safety tests, and electrocardiograms (ECGs)

    Phase 2a
    • ACR 20 at week 12
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout study, Week 12
    E.5.2Secondary end point(s)
    Phase 1b
    • AMG 592 serum concentration and PK parameters including, but not
    limited to, maximum observed concentration (Cmax), the time of maximum observed concentration (Tmax), and area under the concentration-time curve (AUCtau) after the first and last doses. Area under the concentration-time curve
    over the dosing interval will be calculated & reported for each dosing regimen.
    • Anti-AMG 592 antibodies and
    cross-reactivity to IL-2.
    • Anti-AMG 592 and anti-IL 2 neutralizing antibodies
    Phase 2a
    • ACR 50/70 at weeks 12
    • Disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS28-ESR) score and change from baseline at week 12
    • Disease activity score (28 joint) calculated using the C-reactive protein formula
    (DAS-28-CRP) score and change from baseline at week 12
    Treatment-emergent adverse events.
    • Clinically significant changes in vital signs, laboratory safety tests
    - AMG 592 serum concentration and PK parameters
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout study, Week 12
    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 No
    E.6.7Pharmacodynamic No
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase I/II
    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 No
    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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    Bulgaria
    Czech Republic
    Germany
    Mexico
    New Zealand
    Poland
    Romania
    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
    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 months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    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: 102
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 51
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 97
    F.4.2.2In the whole clinical trial 153
    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
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-03-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-12-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-05-13
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