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    Summary
    EudraCT Number:2015-001341-86
    Sponsor's Protocol Code Number:IFN-K-002
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-11-10
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-001341-86
    A.3Full title of the trial
    A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study to
    Evaluate the Neutralization of the Interferon Gene Signature and the
    Clinical Efficacy of IFNa-Kinoid in Adult Subjects with Systemic Lupus
    Erythematosus
    Studio randomizzato, in doppio cieco, controllato verso placebo, di fase IIb per valutare la neutralizzazione della firma genetica dell'interferone e l'efficacia clinica di IFNa-Kinoide in soggetti adulti affetti da lupus eritematoso sistemico
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase IIb study of IFN-K in Systemic Lupus Erythematosus
    Studio di fesa IIb di IFN-K sul lupus eritematoso sistemico
    A.3.2Name or abbreviated title of the trial where available
    IFN-K-002
    IFN-K-002
    A.4.1Sponsor's protocol code numberIFN-K-002
    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 SponsorNEOVACS
    B.1.3.4CountryFrance
    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 supportNeovacs SA
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNeovacs SA
    B.5.2Functional name of contact pointThérèse Croughs
    B.5.3 Address:
    B.5.3.1Street Address3-5 Impasse Reille
    B.5.3.2Town/ cityParigi
    B.5.3.3Post code75014
    B.5.3.4CountryFrance
    B.5.4Telephone number0033153109300
    B.5.5Fax number0033153109303
    B.5.6E-mailtcroughs@neovacs.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 nameIFN-Kinoid
    D.3.2Product code IFN-K
    D.3.4Pharmaceutical form Emulsion for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeIFN-K DS
    D.3.10 Strength
    D.3.10.1Concentration unit µl/ml microlitre(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number380
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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) Yes
    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 placeboEmulsion for injection
    D.8.4Route of administration of the placeboIntramuscular use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Systemic Lupus Erythematosus
    lupus eritematoso sistemico
    E.1.1.1Medical condition in easily understood language
    Lupus
    Lupus
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10042945
    E.1.2Term Systemic lupus erythematosus
    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 main study (at week 36) is to evaluate the neutralization of the IFN gene signature following treatment with IFN-K, as measured by the change from baseline of the expression of IFN-induced genes and to evaluate the efficacy of treatment with IFN-K using the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response criteria.
    The study will be considered as positive if a statistically significant better effect of IFN-K compared to placebo is observed on the neutralization of the IFN gene signature and if at least a trend favoring IFN-K is observed on the BICLA response.
    L'obiettivo primario dello studio principale (a 36 settimane) ¿ di valutare la neutralizzazione della
    firma genica IFN dopo il trattamento con IFN-K, misurata dalla variazione
    dell'espressione dei geni IFN-indotti rispetto al basale, nonch¿ di valutare
    l'efficacia del trattamento con IFN-K utilizzando i criteri di risposta secondo
    l'indice di valutazione composito Composite Lupus Assessment (BICLA)
    basato sul British Isles Lupus Assessment Group (BILAG).
    Lo studio sar¿ considerate positive se verr¿ osservato un effetto IFN-K significativamente migliore da un punto di vista statistic rispetto al placebo sulla neutralizzazione della firma genica IFN e se verr¿ osservata almeno una tendenza a favore di IFN-K sulla risposta BICLA.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are:
    ¿To evaluate the efficacy of treatment with IFN-K using:
    - The SLE Responder Index [(SRI)-4 and above]
    - The SLE Disease Activity Index-2000 (SLEDAI-2K)
    - The BILAG-2004 index
    - The Safety of Estrogen in Lupus Erythematosus National Assessment-
    SLEDAI (SELENA-SLEDAI) Flare index
    - The Systemic Lupus International Collaborating Clinics/American
    College of Rheumatology-Damage Index for Systemic Lupus
    Erythematosus (SLICC/ACR DI)
    - The Cutaneous Lupus Erythematosus Disease Area and Severity Index
    (CLASI) in patients with cutaneous lesions at baseline
    -The Lupus Low Disease Activity State (LLDAS)
    ¿To evaluate the immune response induced by IFN-K
    - Anti-IFNa antibody response
    - Anti-Keyhole Limpet Hemocyanin (KLH) antibody response
    - Anti-IFNa antibody neutralizing capacities
    ¿To assess the safety of IFN-K emulsified with ISA 51 VG
    ¿Valutare l'efficacia del trattamento con IFN K utilizzando:
    - indice di risposta SLE Responder Index [punteggio (SRI) 4 e superiore]
    - indice di attivit¿ della malattia SLE Disease Activity Index 2000 (SLEDAI 2K)
    - indice BILAG 2004
    - indice di esacerbazione Safety of Estrogen in Lupus Erythematosus National Assessment
    - indice Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index per il lupus eritematoso sistemico
    - indice Cutaneous Lupus Erythematosus Disease Area and Severity Index in pazienti che presentano lesioni cutanee al basale
    -Stadio della bassa attivitá di malattia del Lupus (Lupus Low Disease Activity State -LLDAS)
    ¿Valutare la risposta immunitaria indotta da IFN K
    - risposta anticorpale anti IFNa
    - risposta anticorpale anti emocianina da Megathura crenulata
    - capacit¿ neutralizzanti gli anticorpi anti-IFN-K
    ¿Valutare la sicurezza di IFN K emulsionato con ISA 51 VG
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Has had a diagnosis of SLE according to current ACR criteria (4 of 11 ACR criteria)
    2. Has SLEDAI-2K = 6
    3. Has at least 1 BILAG A and/or at least 2 BILAG B
    4. Has a positive IFN gene signature by RT-qPCR as assessed on a limited number of genes
    5. Has anti-nuclear antibodies (ANA) = 1:160 and/or anti-dsDNA antibodies = 7.0 IU/mL
    6. Be a male or female, aged between 18 and 65 years, inclusive, at the time of the screening visit
    7. Agrees to receive influenza vaccination during each influenza season of the study period
    8. Currently receiving at least one of the following treatment:
    • Corticosteroids (CS) at a dose of = 20 mg of prednisone equivalent/day
    • Antimalarial drugs (hydroxychloroquine [HCQ] or chloroquine [CQ]); the patient must have been treated since at least 8 weeks and on stable
    dose for at least 4 weeks prior to first planned administration of the study product
    • Methotrexate (MTX); the patient must have been treated and be on stable dose (= 20 mg/week) for at least 12 weeks prior to the first planned administration of the study product
    • Azathioprine (AZA); the patient must have been treated and be on a stable dose (= 2.5 mg/kg/day) for at least 12 weeks prior to the first planned administration of the study product
    • Mycophenolate mofetil (MMF), the patient must have been treated and be on stable dose (= 2 g/day) for at least 12 weeks prior to the first planned administration of the study product
    9. Study patient and his/her partner has to use effective method of contraception for the duration of the study including the extended follow-up period.
    Note: If of child-bearing potential, effective contraception methods
    include:
    - Female sterilization (have had surgical bilateral oophorectomy with or
    without hysterectomy) or tubal ligation at least 6 weeks prior to the first
    planned administration of the study product. In case of oophorectomy
    alone, the reproductive status of the woman must be confirmed by
    follow up hormone level assessment.
    - Male sterilization (at least 6 months prior to Screening).
    - Combination of the following:
    • Oral, injected or implanted hormonal methods of contraception or
    other forms of hormonal contraception that have comparable efficacy
    (failure rate <1%), for example hormone vaginal ring or transdermal
    hormone contraception or
    • Placement of an intrauterine device (IUD) or intrauterine system
    (IUS)
    • Barrier methods of contraception: condom or occlusive cap
    (diaphragm or cervical/vault caps) with spermicidal
    foam/gel/film/cream/vaginal suppository
    Women are considered post-menopausal and not of child bearing
    potential if they have had 12 months of natural (spontaneous)
    amenorrhea with an appropriate clinical profile (e.g. age appropriate,
    history of vasomotor symptoms) or have had surgical bilateral
    oophorectomy (with or without hysterectomy) or tubal ligation at least
    six weeks ago. In the case of oophorectomy alone, she is considered not
    of child bearing potential only when the reproductive status of the
    woman has been confirmed by follow up hormone level assessment.
    10. Is able and willing to comply with the requirements of the study
    protocol (e.g., completion of the diary cards, return for follow-up visits),
    in the opinion of the Investigator
    11. Has provided written informed consent
    1.Presenza di diagnosi di LES sulla base dei vigenticriteri ACR (4 criteri ACR su 11)
    2.Punteggio SLEDAI 2K = 6
    3.Presenza di almeno 1 BILAG A e/o almeno 2 BILAG B
    4.Presenza della firma genetica dell’ IFN determinata mediante RT qPCR, valutata su un numero limitato di geni
    5.Presenza di anticorpi antinucleo (ANA) = 1:160 e/o anticorpi anti dsDNA = 7,0 UI/mL
    6.Paziente maschio o femmina, di età compresa tra 18 e 65 anni compiuti al momento della visita di screening
    7.Consenso alla vaccinazione antinfluenzale durante ogni stagione influenzale del periodo dello studio
    8.Attualmente in terapia con uno dei seguenti trattamenti:
    •corticosteroidi (CS) ad una dose equivalente a = 20 mg/die di prednisone
    •farmaci antimalarici (idrossiclorochina [HCQ] o clorochina [CQ]); il paziente deve essere in terapia da almeno 8 settimane e ad una dose stabile da almeno 4 settimane prima della prima somministrazione programmata del farmaco sperimentale
    •metotrexato (MTX); il paziente deve essere in terapia ad una dose stabile (= 20 mg/settimana) da almeno 12 settimane prima della prima somministrazione programmata del farmaco sperimentale
    •azatioprina (AZA); il paziente deve essere in terapia ad una dose stabile (= 2,5 mg/kg/die) da almeno 12 settimane prima della prima somministrazione programmata del farmaco sperimentale
    •micofenolato mofetile (MMF); il paziente deve essere in terapia ad una dose stabile (= 2 g/die) da almeno 12 settimane prima della prima somministrazione programmata del farmaco sperimentale
    9.I pazienti partecipanti allo studio e i relativi partner devono far uso di metodi contraccettivi efficaci per l'intera durata dello studio, compreso il period esteso di follow-up.
    10.Paziente in grado e disposto, secondo il parere dello sperimentatore, a rispettare i requisiti del protocollo dello studio (ad es., compilazione delle schede diario, presentarsi alle visite di follow up)
    11.Paziente che ha fornito il consenso informato scritto
    E.4Principal exclusion criteria
    1.Has active, severe lupus nephritis as defined either by the immediate need for cyclophosphamide treatment or by renal BILAG A
    2.Has active, severe, neuropsychiatric SLE, defined as neuropsychiatric BILAG A
    3.During the 4 months prior to the first planned administration of the study product, has been treated with corticosteroids (CS) at a dose of>20mg of prednisone equivalent/day for >7 consecutive days 4. Is currently receiving or has received pulse dose CS (= 250 mg prednisone equivalent/day) within 3 months prior to the first planned administration of the study product
    5.Has received potent immunosuppressive drugs such as cyclophosphamide, cyclosporine A, oral tacrolimus within 3 months prior to the first planned administration of the study product
    6.Has received abatacept, sifalimumab, rontalizumab, anifrolumab, belimumab, TNF antagonists or another registered or investigational biological therapy within 6months prior to the first planned administration of the study product
    7.Has received anti-B-cell therapy (e.g., rituximab, epratuzumab) within 12months prior to the first planned administration of the study product
    8.Has significant ECG abnormalities that are clinically relevant and preclude study eligibility in the Investigator's opinion
    9.Has inflammatory joint or skin disease other than SLE that may interfere with study assessments
    10.Has any laboratory abnormality that is clinically relevant and precludes study entry in the Investigator's opinion
    11.Has a history of malignant cancer, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma
    12.Has frequent recurrences of oral or genital herpes simplex lesions (= 6 occurrences during the 12months prior to first study product administration)
    13.Has had an episode of shingles during the 12months prior to the first planned administration of the study product
    14.Has no IgG against herpes simplex virus (HSV-1 and HSV-2), VZV, CMV or EBV
    15.Is positive for HTLV 1-2 antibodies, HIV antibodies, HCV antibodies, or HBsAg
    16.Is at high risk of significant infection and/or has any current signs or symptoms of infection at entry or has received intravenous antibiotics within 2 months prior to the first planned administration of the study product
    17.Has received any live vaccine within 3 months prior to the first planned administration of the study product (e.g. nasal flu vaccine, oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, Japanese encephalitis vaccine, dengue vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, BCG vaccine, oral typhoid vaccine)
    18.Has used any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, or any investigational or nonregistered vaccine within 30 days prior to the first planned administration of the study product
    19.Has a history of chronic alcohol and/or drug abuse within 6 months prior to the first planned administration of the study product
    20.Is breastfeeding, pregnant, or planning to become pregnant during the study period
    21.Has known hypersensitivity to any component of the study product
    22.Is high-risk HPV positive by RT-qPCR on a cervical swab at Screening or within 3 months prior to the first planned study product administration
    23.Has cytological abnormalities = HSIL on a cervical swab at Screening or within 3 months prior to the first planned study product administration
    1.Presenza di nefrite lupica severa, attiva, definita da immediata necessità di terapia con ciclofosfamide o da BILAG A renale
    2.Presenza di LES neuropsichiatrico severo, attivo, definito come BILAG A neuropsichiatrico
    3.Paziente trattato con CS ad una dose prednisone-equivalente >20mg/die per >7gg consecutivi nei 4 mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    4.Attualmente in terapia o precedentemente trattato con CS in dosaggio pulsato (dose prednisone-equivalente=250mg/die) nei 3mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    5.Precedente terapia con potenti farmaci immunosoppressori, quali ciclofosfamide, ciclosporina A, tacrolimus orale, nei 3mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    6.Precedente terapia con abatacept, sifalimumab, rontalizumab, anifrolumab, belimumab, TNF-antagonisti o altra terapia con agenti biologici registrati o sperimentali nei 6mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    7.Precedente terapia anti-linfociti B (ad es., rituximab, epratuzumab) nei 12mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    8.Presenza di significative anomalie ECG clinicamente importanti e che,secondo il parere dello sperimentatore,precludono la partecipazione allo studio
    9.Presenza di patologia infiammatoria articolare o cutanea diversa dal LES, che potrebbe interferire con le valutazioni dello studio
    10.Anomalie clinicamente importanti nei referti di laboratorio che,secondo il parere dello sperimentatore,precludono l'entrata nello studio
    11.Anamnesi di neoplasia maligna,con l'eccezione delle seguenti neoplasie trattate: carcinoma cervicale in situ, carcinoma basocellulare o carcinoma squamocellulare dermatologico.
    12.Frequenti recidive di lesioni orali o genitali da herpes simplex (= 6recidive nei 12mesi precedenti alla prima somministrazione del prodotto sperimentale)
    13. Comparsa di un episodio di herpes zoster nei 12mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    14. Assenza di IgG verso il virus dell'herpes simplex (HSV-1 e HSV-2), VZV, il CMV o il EBV
    15.Positività per gli anticorpi anti-HTLV 1-2, anticorpi anti-HIV, anticorpi anti-epatite C, o HBsAg
    16.Paziente ad alto rischio di infezione importante e/o che presenta segni e sintomi di infezione al momento dell'entrata nello studio o precedente terapia con antibiotici endovenosi nei 2mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    17.Precedente vaccinazione con vaccino vivo nei 3mesi precedenti alla prima somministrazione programmata del prodotto sperimentale (ad es., vaccino antinfluenzale nasale, vaccino orale antipolio, vaccino MPR, vaccino contro la febbre gialla, contro l'encefalite giapponese, contro la febbre di Dengue, vaccino antirotavirus, vaccino antivaricella, vaccino antizoster, vaccino BCG, vaccino antitifico orale)
    18.Uso di qualsiasi prodotto sperimentale o non registrato nei 30 giorni o 5 emivite, a seconda di quale periodo sia il più lungo, o qualsiasi vaccino sperimentale o non registrato nei 30 giorni precedenti alla prima somministrazione programmata del prodotto sperimentale
    19.Anamnesi di abuso cronico di alcol e/o sostanze nei 6 mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    20.Paziente femmina che allatta con latte materno, è in gravidanza o prevede di iniziare una gravidanza durante il periodo dello studio
    21.Presenza di nota ipersensibilità a qualsiasi componente del prodotto sperimentale
    22.Positività verso il HPV ad alto rischio, confermata mediante RT-qPCR, o tampone cervicale allo screening o nei 3 mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    23.Presenza di anomalie citologiche = HSIL su un tampone cervicale allo screening o nei 3mesi precedenti alla prima somministrazione programmata del prodotto sperimentale
    E.5 End points
    E.5.1Primary end point(s)
    Two co-primary endpoints will be evaluated in the trial:
    ¿ Change from baseline in the expression of IFN-induced genes at Week 36.
    ¿ Response to treatment with IFN-K as measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response criteria at Week 36:
    - All BILAG A scores at baseline improve to B/C/D and all BILAG B scores improve to C/D at Week 36
    and
    - No BILAG worsening in other body systems: no new BILAG A or = 2 new BILAG B scores at Week 36
    and
    - No worsening in SLEDAI-2K total score at Week 36 compared with baseline
    and
    - No deterioration in PGA (< 10% worsening) on VAS 100 mm at Week 36 compared with baseline
    and
    - No addition or increased dose level of anti-malarial drugs or immunosuppressive drugs or corticosteroids between Week 24 and Week 36
    Durante lo studio saranno valutati due endpoint coprimari:
    ¿ Variazione dell'espressione genica IFN-indotta dal basale alla
    Settimana 36.
    ¿ Risposta al trattamento con IFN-K, misurata mediante i criteri di
    risposta secondo l'indice di valutazione composito Composite Lupus
    Assessment (BICLA) basato sul British Isles Lupus Assessment Group
    (BILAG) alla Settimana 36:
    ¿ tutti i punteggi BILAG A al basale migliorati a B/C/D e
    tutti i punteggi BILAG B migliorati a C/D alla
    Settimana 36
    e
    ¿ nessun peggioramento del BILAG in altri sistemi
    corporei: nessun nuovo punteggio BILAG A o nuovi
    punteggi = 2 BILAG B alla Settimana 36
    e
    ¿ nessun peggioramento del punteggio totale SLEDAI-2K
    alla Settimana 36 rispetto al basale
    e
    ¿ nessun deterioramento nel PGA (peggioramento < 10%)
    sulla VAS 100 mm alla Settimana 36 rispetto al basale
    e
    ¿ nessuna aggiunta o nessun aumento del livello di dose di
    farmaci antimalarici o immunosoppressori o di
    corticosteroidi tra la Settimana 24 e la Settimana 36
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 36
    Settimana 36
    E.5.2Secondary end point(s)
    ¿ Response to treatment with IFN-K, as measured by the SLE Responder Index (SRI)-4 response criteria at Week 36:
    - Reduction = 4 points in SELENA-SLEDAI
    and
    - No new BILAG A
    and
    - No more than 1 new BILAG B
    and
    - No deterioration in PGA (< 10% worsening) on VAS 100 mm compared with baseline; ¿ Response to treatment with IFN-K, as measured by SLEDAI response, defined as a reduction of the SLEDAI-2K score of at least 4 points at Week 36 compared to baseline; ¿ Response to treatment with IFN-K, as measured by BILAG grade changes by body system; Response to treatment with IFN-K, as measured by incidence of SLE flare
    (SELENA SLEDAI flare index, BILAG flares); Response to treatment with IFN-K, as measured by SLICC/ACR-DI; Response to treatment with IFN-K, as measured by Cutaneous LE Disease
    Area and Severity Index (CLASI); At timepoints specified on the flow chart, Geometric Mean Titers (GMT) and
    seroconversion rates for:
    ¿ Anti-IFNa binding antibody titers
    ¿ Anti-IFNa neutralizing antibody titers
    ¿ Anti-KLH binding antibody titers; Occurrence, intensity and relationship of any solicited local and systemic
    AEs during a 7-day follow-up period (i.e. day of study product
    administration and 6 subsequent days) after each IFN-K or placebo dose; Occurrence, intensity and relationship of unsolicited local and systemic
    AEs occurring throughout the study period; Occurrence and relationship of all SAEs occurring throughout the study
    period; Occurrence and intensity of solicited injection site reactions 1 hour post
    study product administration; Occurrence and intensity of solicited systemic reactions 1 hour post study
    product administration; Hematological and biochemical levels within or outside the normal ranges
    and percent change from baseline at each visit; Occurrence, intensity and relationship of any abnormality in physical
    examination, vital signs, 12-lead ECG, clinical laboratory evaluations; Rate and severity of viral infe; Evaluation of clinical response by assessing disease activity using: PGA
    scores, Number of SLE flares, Time to first SLE flare in patients, 28-
    Tender and Swollen Joint Counts, Joint Pain VAS and incidence of patient
    requiring change in lupus therapy (intensification and/or addition of drugs); Quality of life using:
    ¿ Changes in the SF-36 score: Physical Component Summary (PCS)
    and Mental Component Summary (MCS) scores
    ¿ FACIT fatigue score; Evaluation of biological response by assessing :
    - Changes in the levels of auto-antibodies (anti-dsDNA, anti-Smith
    antigen [anti-Sm], anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-cardiolipin,
    and anti-¿2-glycoprotein I antibodies)
    - Changes in the levels of biomarkers (C3, C4, CH50)
    - Neutralizing Anti-IFNa antibodies towards IFNa subtypes
    - Anti-IFNa and anti-KLH antibody isotyping
    - IFN¿ cross neutralization
    - Anti-hemagglutinin antibody response; Attainment of Lupus Low Disease Activity State (LLDAS) as assessed at each extended follow up visit
    ¿Risposta al trattamento con IFN K, misurata sulla base dei criteri di risposta SLE Responder Index (SRI) 4 alla Settimana 36:
    ¿ riduzione = 4 punti nel SELENA SLEDAI
    e
    ¿ nessun nuovo BILAG A
    e
    ¿ non pi¿ di 1 nuovo BILAG B
    e
    ¿ nessun deterioramento nel PGA (peggioramento < 10%) sulla VAS 100 mm rispetto al basale; ¿ Risposta al trattamento con IFN K, misurata tramite la risposta SLEDAI, definita come una riduzione di almeno 4 punti nel punteggio SLEDAI 2K alla Settimana 36 rispetto al basale; ¿Risposta al trattamento con IFN K, misurata dalle variazioni del grado BILAG per sistema corporeo; Risposta al trattamento con IFN-K, misurata dall'incidenza di
    esacerbazioni del LES (indice di esacerbazione SELENA SLEDAI,
    esacerbazioni BILAG); Risposta al trattamento con IFN-K, misurata tramite SLICC/ACR-DI; Risposta al trattamento con IFN-K, misurata tramite l'indice Cutaneous LE
    Disease Area and Severity Index (CLASI); Ai time-point specificati nel diagramma di flusso, la media geometrica dei
    titoli (GMT) e i tassi di sieroconversione per:
    ¿ Titoli degli anticorpi leganti anti-IFNa
    ¿ Titoli degli anticorpi neutralizzanti anti-IFNa
    ¿ Titoli degli anticorpi leganti anti-KLH; Insorgenza, intensit¿ e relazione di qualsiasi evento avverso (AE) locale e
    sistemico sollecitato durante un periodo di follow-up di 7 giorni (ossia, il
    giorno della somministrazione del prodotto sperimentale e nei 6 giorni
    successivi) dopo la somministrazione di ogni dose di IFN-K o placebo; Insorgenza, intensit¿ e relazione degli AE locali e sistemici non sollecitati
    che si manifestano durante l'intero periodo dello studio; Insorgenza e relazione di tutti gli eventi avversi seri (SAE) che si
    manifestano durante l'intero periodo dello studio; Insorgenza e intensit¿ delle reazioni sollecitate al sito di iniezione 1 ora
    dopo la somministrazione del prodotto sperimentale; Insorgenza e intensit¿ delle reazioni sistemiche sollecitate 1 ora dopo la
    somministrazione del prodotto sperimentale; Livelli ematologici e biochimici che rientrano o non rientrano negli
    intervalli normali e variazione percentuale dal basale ad ogni visita; Insorgenza, intensit¿ e relazione di qualsiasi anomalia nell'esame obiettivo,
    parametri vitali, ECG a 12 derivazioni, analisi cliniche di laboratorio; ctions Tasso e severit¿ delle infezioni virali; Valutazione della risposta clinica mediante la valutazione della malattia
    basata su: punteggi PGA, numero di esacerbazioni del LES, tempo alla
    prima esacerbazione del LES nei pazienti, conta a 28 articolazioni
    tumefatte e dolenti, VAS per il dolore articolare e incidenza dei
    cambiamenti di terapia del paziente per il lupus (intensificazione e/o
    aggiunta di farmaci) che si rendono necessari; Qualit¿ della vita valutata sulla base di:
    ¿ variazioni del punteggio SF-36: punteggi del riassunto della
    componente fisica (PCS) e della componente psichica (MCS)
    ¿ punteggio della scala FACIT-Fatigue
    ; Valutazione della risposta biologica determinata tramite:
    - variazioni dei livelli degli autoanticorpi (anticorpi anti-dsDNA, verso l¿antigene anti-Smith [anti-Sm], anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-cardiolipina e anti-¿2-glicoproteina I)
    - variazioni dei livelli dei biomarker (C3, C4, CH50)
    - anticorpi anti-IFNa neutralizzanti verso i sottotipi IFNa
    - isotipizzazione degli anticorpi anti-IFNa e anti-KLH - neutralizzazione crociata di IFN¿
    - risposta anticorpale anti-emoagglutinina; Raggiungimento dell’indice dello stadio di bassa malattia del Lupus (Low Disease Activity State - LLDAS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 36; Week 36; end of trial; Week 36; Week 36; Week 36; At timepoints specified on the flow chart; Week 36; throughout the study period; throughout the study
    period; 1 hour post
    study product administration; 1 hour post study
    product administration; at each visit; Week 36; throughout the study period; Week 36; Week 36; Week 36; Week 36
    Settimana 36; Settimana 36; fine studio; settimana 36; Settimana 36; settimana 36; time-point specificati nel diagramma di flusso; Settimana 36; durante l'intero periodo dello studio; durante l'intero periodo dello studio; 1 ora
    dopo la somministrazione del prodotto sperimentale; 1 ora dopo la
    somministrazione del prodotto sperimentale; ad ogni visita; settimana 36; durante l'intero periodo di studio; Settimana 36; Settimana 36; Settimana 36; Settimana 36
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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 Yes
    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 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 concerned7
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Belgium
    Chile
    Colombia
    Croatia
    France
    Georgia
    Germany
    Italy
    Korea, Democratic People's Republic of
    Korea, Republic of
    Mexico
    Moldova, Republic of
    Netherlands
    Peru
    Philippines
    Poland
    Russian Federation
    Taiwan
    Thailand
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months7
    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: 178
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 77
    F.4.2.2In the whole clinical trial 178
    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)
    Following the 12-week Maintenance Period, patients will enter the 12-week Follow-up Period and subsequently enter in an Extended 240 week Follow-up Period. The visit at Week 276 will be considered as the last planned visit.
    If patients remain positive for anti-IFNa neutralizing antibodies after this Extended Follow up Period, they will be proposed to be enrolled in another 5-year follow up study to confirm the favorable safety profile of IFN-K.
    Dopo il Maintenance Period di 12w, i pazienti entreranno nel periodo di FU di 12 w e successivamente saranno seguiti durante un periodo di FU esteso di 240w. La visita alla w276 sará considerata l'ultima visita programmata. Se i pazienti rimarrano positivi agli anticorpi neutralizzanti anti-IFNa dopo questo periodo esteso di FU, essi avranno la possibilitá di essere reclutati in un altro studio di fu della durata di 5 anni, per confermare il profilo di sicurezza favorevole di IFN-K.
    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 Decision2015-09-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-19
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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