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    Summary
    EudraCT Number:2020-003509-72
    Sponsor's Protocol Code Number:20200234
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    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 ConcernedAustria - BASG
    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 GmbH
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street AddressFranz-Josefs-Kai 47
    B.5.3.2Town/ cityWien
    B.5.3.3Post code1010
    B.5.3.4CountryAustria
    B.5.4Telephone number+43150217
    B.5.5Fax number+4315021720
    B.5.6E-mailmedinfo-at@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 in hands and wrists; 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 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 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
    Austria
    France
    Poland
    Bulgaria
    Spain
    Switzerland
    Greece
    Italy
    Russian Federation
    Turkey
    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 months8
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months8
    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 state5
    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 Decision2021-05-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-05-22
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