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    Summary
    EudraCT Number:2020-003509-72
    Sponsor's Protocol Code Number:20200234
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-05-11
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2020-003509-72
    A.3Full title of the trial
    A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Efavaleukin Alfa in Subjects with Active Systemic Lupus Erythematosus With Inadequate Response to Standard of Care Therapy (VIOLET)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and Safety of Efavaleukin Alfa in Subjects with Active Systemic Lupus
    Erythematosus
    A.4.1Sponsor's protocol code number20200234
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04680637
    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 Biotechnologia Sp. z o.o.
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street Addressul. Pulawska 145
    B.5.3.2Town/ cityWarsaw
    B.5.3.3Post code02-715
    B.5.3.4CountryPoland
    B.5.4Telephone number+48 22 581 30 00
    B.5.5Fax number+48 22 581 30 01
    B.5.6E-mailmedinfo-pol@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 nameEfavaleukin Alfa
    D.3.2Product code AMG 592
    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 INNEFAVALEUKIN ALFA
    D.3.9.2Current sponsor codeAMG 592
    D.3.9.3Other descriptive nameRECOMBINANT FACTOR FC FUSION PROTEIN
    D.3.9.4EV Substance CodeSUB195522
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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
    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
    Active Systemic Lupus Erythematosus
    E.1.1.1Medical condition in easily understood language
    Systemic Lupus Erythematosus
    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 21.1
    E.1.2Level LLT
    E.1.2Classification code 10025139
    E.1.2Term Lupus erythematosus systemic
    E.1.2System Organ Class 100000004859
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Evaluate the efficacy of efavaleukin alfa at week 52, as measured by the SRI-4 response
    E.2.2Secondary objectives of the trial
    - Evaluate the efficacy of efavaleukin alfa at week 52, as measured by the BICLA index responses
    - Evaluate the efficacy of efavaleukin alfa at week 52, as measured by LLDAS response
    - Evaluate the efficacy of efavaleukin alfa at week 52, as measured by OCS tapering
    - Evaluate the efficacy of efavaleukin alfa at week 24, as measured by SRI-4 response
    - Evaluate the efficacy of efavaleukin alfa at week 24, as measured by the BICLA index responses
    - Evaluate the efficacy of efavaleukin alfa at weeks 24 and 52, as measured by hSLEDAI
    - Evaluate the efficacy of efavaleukin alfa on joints and skin
    - Evaluate the efficacy of efavaleukin alfa using BILAG score
    - Evaluate the efficacy of efavaleukin alfa using patient reported outcomes
    - Characterize the safety of efavaleukin alfa
    - Characterize the PK of efavaleukin alfa
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Screening:
    101 Subject has provided informed consent prior to initiation of any
    study specific activities/procedures.
    102 Age ≥ 18 years to 75 years at screening.
    103 Fulfills classification criteria for SLE according to the 2019
    EULAR/ACR classification criteria for SLE (Aringer et al, 2019), with
    antinuclear antibody ≥ 1:80 by immunofluorescence on Hep-2 cells being present at screening. Anti-dsDNA results based on the Phadia method
    will be used for the purposes of hSLEDAI scoring during screening and
    throughout the study.
    110 Hybrid SLEDAI score ≥ 6 points with a "Clinical" hSLEDAI score ≥ 4
    points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without
    the inclusion of points attributable to laboratory results, including urine
    and immunologic parameters. Including the following protocol specific
    rules:
    - Arthritis: for hSLEDAI scoring purposes, a minimum of 3 joints with
    pain and signs of inflammation (ie, tenderness with swelling or effusion)
    must involve small joints in the hands, wrists, or a combination of joints
    in hands and wrists.
    - Alopecia: subjects should have active hair loss without scarring; should
    neither have alopecia areata nor androgenic alopecia; and should have a
    CLASI activity score for alopecia ≥2.
    - Oral ulcers: ulcers location and appearance must be documented by the
    investigator.
    - Scleritis and episcleritis: the presence of stable SLE-related scleritis
    and episcleritis (ie, that will likely not require initiation/increase in
    immunosuppressants/immunomodulators as outlined in the
    inclusion/exclusion criteria) must be documented by an ophthalmologist
    and other causes excluded.
    - Renal: subjects with urine protein/creatinine ratio < 2000 mg/g (or
    equivalent) in a clean catch spot urine sample can enroll and be scored
    in the hSLEDAI, provided the subject has a clinical hSLEDAI ≥ 4.
    - Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must
    be accompanied by objective findings to be scored in the hSLEDAI.
    105 BILAG index score (BILAG 2004) of ≥ 1 A item or ≥ 2 B items.
    106 Must be taking ≥ 1 of the following SLE treatments (or regional
    equivalent):
    hydroxychloroquine, chloroquine, quinacrine, mycophenolate mofetil,
    azathioprine, methotrexate, dapsone, or oral calcineurin inhibitors, or
    OCS. A subject may enter the study on OCS alone (prednisone ≥ 10
    mg/day or equivalent) only if the subject has previously documented
    trial of anti-malarial or immunosuppressant treatment for SLE. Subjects
    must be on a stable dose for ≥ 8 weeks prior to screening for all
    antimalarials and
    immunosuppressants, with the exception of OCS doses which must be
    stable for ≥ 2 weeks prior to screening.
    107 For subjects taking OCS, the dose must be ≤ 20 mg/day of
    prednisone or OCS equivalent, and the dose must be stable for ≥ 2
    weeks prior to screening visit.
    111. For France, affiliation to a social security scheme is required.
    Day 1 (Baseline):
    The baseline/day 1 visit should occur after confirmation of eligibility by
    the adjudication team within 33 days after the screening visit. At the
    baseline/day 1 visit, the following 2 criteria should be assessed prior to
    randomization:
    108 Stability of SLE treatments: OCS and other
    immunosuppressants/immunomodulator agents and doses must be
    stable since screening visit.
    109 Disease activity: active disease as indicated by clinical hSLEDAI
    score ≥ 4 must be observed (clinical hSLEDAI score is the hSLEDAI
    assessment score without the inclusion of points attributable to
    laboratory results including urine and immunologic parameters).
    E.4Principal exclusion criteria
    231 Lupus nephritis if any of the following are present:
    urine protein creatinine ratio ≥ 2000 mg/g at screening, OR requiring
    induction therapy currently or within 1 year prior to screening, OR
    histological evidence of diffuse proliferative glomerulonephritis within
    12 weeks prior to screening.
    202 Active CNS lupus within 1 year prior to screening including, but not
    limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy,
    demyelinating syndrome, optic neuritis, psychosis, seizures, or
    transverse myelitis.
    232 Currently present or within 1 year prior to screening a diagnosis of
    any chronic inflammatory disease other than SLE which would interfere
    with SLE disease assessment.
    204 History of any disease other than SLE that has required treatment
    with oral or parenteral corticosteroids for > 2 weeks within 4 months
    prior to screening.
    205 Active infection for which anti-infectives are indicated currently or
    within 4 weeks prior to screening visit OR presence of serious infection,
    defined as requiring hospitalization or intravenous anti-infectives within
    8 weeks prior to screening visit.
    206 Active tuberculosis or latent tuberculosis with no documented past
    history of adequate treatment per local standard of care.
    207 Positive test for tuberculosis during screening defined as: either a
    positive or indeterminate QuantiFERON®-TB or T-spot test OR positive
    purified protein derivative (PPD) (≥ 5 mm of induration at 48 to 72
    hours after test is placed).
    233 Positive for hepatitis B surface antigen (HBsAg); or positive for
    hepatitis B core antibody (HBcAb). A positive hepatitis B surface
    antibody (HBsAb) without history of hepatitis B infection (ie, positive
    HBsAg, negative HBsAg and negative HBcAb) is allowed.
    234 Positive for hepatitis C antibody
    210 Known history of HIV or positive HIV test at screening.
    235 Presence of 1 or more significant concurrent medical conditions,
    including but not limited to the following: poorly controlled diabetes or
    hypertension, symptomatic heart failure, myocardial infarction or
    unstable angina pectoris within the past 12 months prior to screening,
    severe chronic pulmonary disease requiring oxygen therapy, multiple
    sclerosis or any other demyelinating disease.
    212 Any history of malignancy with the following exceptions:
    resolved non-melanoma skin cancers > 5 years prior to screening
    resolved cervical carcinoma > 5 years prior to screening
    resolved breast ductal carcinoma in situ > 5 years of screening
    213 Currently receiving or had treatment with: cyclophosphamide,
    chlorambucil, nitrogen mustard, or any other alkylating agent within 6
    months prior to screening or sirolimus within 4 weeks prior to screening.
    237 Currently receiving or had treatment with a Janus kinase (JAK)
    inhibitor within less than 5 drug half-lives prior to screening.
    215 Currently receiving or had treatment with an immune checkpoint
    inhibitor
    216 Currently receiving or had treatment within 12 months prior to
    screening with T-cell depleting agents
    217 Currently receiving or had treatment with an IL-2 based therapy
    238 Current or previous treatment with a biologic agent with
    immunosuppressive/immunomodulatory activity as follows: rituximab
    within 6 months prior to screening; abatacept, belimumab, and
    anifrolumab within the past 3 months prior to screening; other biologics
    within < 5 drug half-lives prior to screening.
    219 Subjects who have received intraarticular, intralesional, or
    intramuscular corticosteroids within 2 weeks prior to screening or
    intravenous corticosteroids within 6 weeks prior to screening.
    220 Subjects who have received live vaccines within 5 weeks prior to
    screening, or plan to receive live vaccines during the treatment period
    and up to 6 weeks after the end of treatment period in the study.
    221 Currently receiving treatment in another investigational device or
    drug study.
    222 Ending a treatment with an investigational drug or investigational
    device less than 3 months or 5 half-lives from the last dose of the
    investigational drug at screening.
    236 Presence of laboratory abnormalities at screening
    224 Any other laboratory abnormality, which in the opinion of the
    investigator, poses a safety risk, will prevent the subject from
    completing the study or will interfere with the interpretation of the study
    results, or might cause the study to be detrimental to the subject
    E.5 End points
    E.5.1Primary end point(s)
    - SRI-4 response at week 52
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 52
    E.5.2Secondary end point(s)
    - BICLA response at week 52
    - LLDAS response at week 52
    - Reduction of OCS to ≤ 7.5 mg/day by week 44 and sustained through
    week 52 in subjects with a baseline OCS dose ≥ 10 mg/day
    - SRI-4 response at week 24
    - BICLA response at week 24
    - hSLEDAI response (ie, reduction ≥ 4 points from baseline) at
    week 24
     hSLEDAI response (ie, reduction ≥ 4 points from baseline) at
    week 52
    - Improvement from baseline in tender and swollen joint count
    ≥ 50% at weeks 8, 12, 24, 36, and 52 in subjects with ≥ 6 tender and
    swollen joints involving hands and wrists at baseline
    - Improvement from baseline in CLASI activity score ≥ 50% at
    week 8, 12, 24, 36, and 52 in subjects with a CLASI activity
    score ≥ 8 at baseline
    - Annualized flare rate (as measured by BILAG score designation of “worse” or “new” resulting in a B score in ≥ 2 organs or an A score in ≥ 1 organ) over 52 weeks
    - Change from baseline in fatigue standardized score using the PROMIS Fatigue SF 7a at week 12, 24, 36, and 52
    - Change from baseline in the physical component score, mental
    component score and individual domains of the SF 36 v2 at week
    12, 24, 36, and 52
    - Change from baseline in the domain scores on the Lupus QoL
    at weeks 12, 24, 36, and 52
    - Treatment-emergent adverse events
    - Serious adverse events
    - Clinically significant changes in laboratory values and vital signs
    - Trough and sparse post-dose serum concentrations of efavaleukin alfa
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 8, 12, 24, 36, and 52
    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) 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 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    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
    Chile
    Colombia
    Hong Kong
    Japan
    Korea, Republic of
    Mexico
    South Africa
    Taiwan
    United States
    Switzerland
    Russian Federation
    Turkey
    Austria
    Bulgaria
    France
    Greece
    Italy
    Poland
    Spain
    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
    Completion of follow-up
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days7
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months8
    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: 215
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 105
    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 110
    F.4.2.2In the whole clinical trial 320
    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)
    6 week safety follow-up
    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 Decision2021-05-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-05-11
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-05-22
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