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    Summary
    EudraCT Number:2021-000665-32
    Sponsor's Protocol Code Number:80202135SJS2001
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-09-08
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2021-000665-32
    A.3Full title of the trial
    A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Nipocalimab in Adults with Primary Sjogren's Syndrome (pSS)
    Studio multicentrico, randomizzato, controllato con placebo, in doppio cieco per valutare l’efficacia e la sicurezza di nipocalimab in adulti affetti da sindrome di Sjögren primaria (SSp)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Nipocalimab in Adults with Primary Sjogren's Syndrome (pSS)
    Uno studio su Nipocalimab in adulti con la sindrome di Sjögren primaria (SSp)
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code number80202135SJS2001
    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 SponsorJANSSEN CILAG INTERNATIONAL NV
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag International NV
    B.5.2Functional name of contact pointClinical Registry Group
    B.5.3 Address:
    B.5.3.1Street AddressArchimedesweg 29
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333CM
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031715242166
    B.5.5Fax number0031715242110
    B.5.6E-mailClinicalTrialsEU@its.jnj.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 namenipocalimab
    D.3.2Product code [M281]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnipocalimab
    D.3.9.1CAS number 2211985-36-1
    D.3.9.2Current sponsor codeM281
    D.3.9.3Other descriptive nameJNJ-80202135
    D.3.9.4EV Substance CodeSUB195356
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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) 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 infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Sjogren's Syndrome
    sindrome di Sjögren primaria
    E.1.1.1Medical condition in easily understood language
    Primary Sjogren's Syndrome
    sindrome di Sjögren primaria
    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 21.0
    E.1.2Level LLT
    E.1.2Classification code 10040766
    E.1.2Term Sjogren's disease
    E.1.2System Organ Class 100000004859
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of nipocalimab in participants with primary Sjogren’s syndrome
    (pSS) versus placebo
    Valutare l’efficacia di nipocalimab in partecipanti con sindrome di Sjögren primaria (SSp) rispetto al placebo
    E.2.2Secondary objectives of the trial
    - To evaluate the safety of nipocalimab
    treatment versus placebo in participants with
    pSS

    - To evaluate the pharmacokinetics (PK) and
    immunogenicity of nipocalimab in
    participants with pSS

    - To evaluate the effect of nipocalimab versus
    placebo on levels of serum biomarkers related
    to pSS
    • Valutare la sicurezza del trattamento con nipocalimab rispetto al placebo nei partecipanti con SSp
    • Valutare la farmacocinetica (PK) e l’immunogenicità di nipocalimab nei partecipanti con SSp
    • Valutare l’effetto di nipocalimab rispetto al placebo sui livelli di biomarcatori sierici correlati alla SSp
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: optional labial salivary gland biopsy sub study

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: sottostudio opzionale di biopsia delle ghiandole salivari labiali
    E.3Principal inclusion criteria
    - Meets classification criteria for primary sjogren's syndrome (pSS) by the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) within 5 years but at least 6 months prior to screening
    - At screening is seropositive for antibodies to pSS-associated antigen A (60 kilodalton [kDa] Ro/sjogren's syndrome-related antigen [SSA])
    - Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) score greater than or equal to (>=) 6 and less than or equal to (<=) 13
    - At least low activity as defined in the biological domain of European League Against Rheumatism (EULAR) and in at least low activity in at least one of the following ESSDAI domains: cutaneous, articular, glandular, constitutional, hematologic, and lymphadenopathy
    - It is recommended that participants are up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, applicable local vaccine labelling, guidelines, and standards-of-care for participants receiving immune-targeted therapy will be followed when determining an appropriate interval between vaccination and study enrollment.
    -Soddisfacimento dei criteri di classificazione della SS primaria secondo il Collegio Americano di Reumatologia (ACR) 2016/Lega europea contro le malattie reumatiche (EULAR; Shiboski, 2017) entro 5 anni ma almeno 6 mesi prima dello screening
    - Allo screening è sieropositivo per gli anticorpi diretti contro l’antigene A associato alla SSp (Ro/SSA da 60 kDa)
    - Punteggio ClinESSDAI totale > =6 e <=13, inclusi
    - Deve dimostrare attività almeno bassa come definito nel dominio biologico dell’ESSDAI
    E
    attività almeno bassa in almeno uno dei seguenti domini ESSDAI: cutaneo, articolare, ghiandolare, costituzionale, ematologico e linfadenopatico.
    - Si raccomanda ai partecipanti di aggiornarsi su tutte le vaccinazioni adeguate all’età prima dello screening, come previsto dalle linee guida mediche locali di routine. Per i partecipanti allo studio che hanno recentemente ricevuto vaccini approvati a livello locale (incluso l’uso autorizzato in caso di emergenza) per la malattia da coronavirus 2019 (COVID-19) prima dell’ingresso nello studio, attenersi all’etichetta del vaccino locale applicabile, alle linee guida e allo standard di cura per i partecipanti che ricevono una terapia immuno-mirata quando si stabilisce un intervallo appropriato tra la vaccinazione e l’arruolamento nello studio
    E.4Principal exclusion criteria
    -Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her pSS or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
    - Comorbidities (for example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months
    - Has any unstable or progressive manifestation of pSS that is likely to warrant escalation in therapy beyond permitted background medications and/or has severely active pSS (clinESSDAI score greater than [>] 13)
    - Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention
    - Has sjogren's syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition (for example, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease [IBD]) is the primary diagnosis or has clinical manifestations that, in the opinion of the
    investigator, are likely to interfere with the investigator's ability to assess pSS manifestations
    - Il soggetto presenta una qualsiasi sindrome da immunodeficienza clinica confermata o sospetta non correlata al trattamento della sua SSp o presenta un’anamnesi familiare di immunodeficienza congenita o ereditaria, a meno che non ne sia stata confermata l’assenza nel partecipante.
    - Presenza di comorbilità (diverse dalla SSp, per es. asma, broncopneumopatia cronica ostruttiva) che abbiano richiesto 3 o più cicli di glucocorticoidi sistemici nei 12 mesi precedenti.
    - Presenza di qualsiasi manifestazione instabile o progressiva di SSp che potrebbe giustificare un’intensificazione della terapia oltre i farmaci di base consentiti e/o SSp gravemente attiva (punteggio clinESSDAI >13)
    - Uso pregresso di ciclofosfamide orale negli ultimi 3 mesi o ciclofosfamide EV nei 6 mesi precedenti la prima somministrazione del trattamento in studio.
    - Presenza di sindromi sovrapposte alla sindrome di Sjögren in cui un’altra condizione infiammatoria autoimmune reumatica o sistemica confermata (ovvero, artrite reumatoide [AR], lupus eritematoso sistemico [LES], sclerodermia, malattia infiammatoria intestinale [IBD]) rappresenta la diagnosi primaria o presenza di manifestazioni cliniche che, a giudizio dello sperimentatore, potrebbero interferire con la capacità dello sperimentatore di valutare le manifestazioni della SSp.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in Clinical European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (clinESSDAI) score at Week 24
    Variazione rispetto al basale nel punteggio dell’Indice clinico di attività della malattia nella sindrome di Sjögren (clinESSDAI) della Lega europea contro le malattie reumatiche (EULAR) alla Settimana 24
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to week 24
    alla settimana 24 rispetto al basale
    E.5.2Secondary end point(s)
    1. Change from baseline in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score at Week 24
    2. Improvement of >=4 points from baseline in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score (minimal clinically important improvement) at Week 24
    3. Improvement of >=4 points from baseline in clinESSDAI score (minimal clinically important improvement) at Week 24
    4. ESSPRI response defined as a decrease of one point or a decrease of >=15% from baseline
    (minimal clinically important improvement) at Week 24
    5. Sjogren's Syndrome Responder Index (SSRI) response defined as >=20% improvement from
    baseline in at least two of five domains (fatigue, oral dryness, ocular dryness, unstimulated whole salivary flow, erythrocyte sedimentation rate) at Week 24
    6. Improvement in disease activity level by >=1 level in at least one clinESSDAI or ESSDAI domain (biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular) at Week 24 - Improvement from baseline in >=3 of 5 composite of relevant endpoints for Sjogren’s Syndrome (CRESS) categories at Week 24
    7. Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
    8. Percentage of Participants with Adverse Events of Special interests (AESIs)
    9. Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs)
    10. Percentage of Participants with Clinically Significant Abnormalities in Vital Signs
    11. Percentage of Participants with Clinically Significant Abnormalities in Laboratory Parameters
    12. Serum Concentration of Nipocalimab Over Time
    13. Number of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])
    14. Number of Participants with Change from Baseline in Biomarkers
    15. Number of Participants with Change from Baseline in Autoantibodies
    • Variazione rispetto al basale nel punteggio dell’Indice EULAR della sindrome di Sjögren riferito dal paziente (ESSPRI) alla Settimana 24
    • Miglioramento di >=4 punti rispetto al basale nel punteggio dell’Indice EULAR di attività della malattia nella sindrome di Sjögren (ESSDAI) (miglioramento minimo clinicamente importante) alla Settimana 24
    • Miglioramento di >=4 punti rispetto al basale nel punteggio clinESSDAI (miglioramento minimo clinicamente importante) alla Settimana 24
    • Risposta ESSPRI definita come una diminuzione di un punto o una diminuzione >=15% rispetto al basale (miglioramento minimo clinicamente importante) alla Settimana 24
    • Risposta dell’Indice di risposta della sindrome di Sjögren (SSRI), definita come miglioramento >=20% rispetto al basale in almeno due di cinque domini (affaticamento, secchezza orale, secchezza oculare, flusso salivare intero non stimolato, velocità di eritrosedimentazione) alla Settimana 24
    • Miglioramento del livello di attività della malattia di >=1 livello in almeno un dominio clinESSDAI o ESSDAI (biologico, ematologico, cutaneo, costituzionale, linfoadenopatia e linfoma e ghiandolare) alla Settimana 24
    • Miglioramento rispetto al basale in >=3 di 5 endpoint compositi rilevanti per le categorie della sindrome di Sjögren (CRESS) alla Settimana 24

    • Numero e percentuale di partecipanti con eventi avversi emergenti dal trattamento (TEAE), eventi avversi di particolare interesse (AESI) ed eventi avversi seri (SAE) emergenti dal trattamento fino alla visita di fine studio
    • Numero e percentuale di partecipanti con anomalie clinicamente significative nei segni vitali e nei test di sicurezza di laboratorio fino alla visita di fine studio
    • Sintesi delle concentrazioni sieriche di nipocalimab nel tempo nei partecipanti che ricevono il trattamento attivo dello studio
    • Incidenza e titoli di anticorpi contro nipocalimab (anticorpi anti-farmaco [ADA] e anticorpi neutralizzanti [NAb]) nei partecipanti che ricevono il trattamento attivo dello studio
    • Variazione rispetto al basale nei biomarcatori
    • Variazione rispetto al basale nei autoanticorpi
    E.5.2.1Timepoint(s) of evaluation of this end point
    secondary endpoint 1-7 at week 24
    secondary endpoint 8-12, up to week 36
    secondary endpoint 13 at week 30
    secondary endpoint 14-16 up t week 36
    endpoint secondario 1-7 alla settimana 24
    endpoint secondario 8-12 fino alla settimana 36
    endpoint secondario 13 alla settimana 30
    endpoint secondario 14-16 fino alla 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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    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 trial3
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA37
    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
    Japan
    Taiwan
    United States
    France
    Germany
    Italy
    Netherlands
    Poland
    Portugal
    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
    last follow-up assessment (8 weeks after the last infusion of study intervention) for the last participant.
    ultima valutazione di follow up (8 settimane dopo l'ultima infusione dell'intervento in studio) per l'ultimo partecipante
    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 months7
    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 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: 135
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 150
    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
    nessuno
    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 Decision2021-11-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-15
    P. End of Trial
    P.End of Trial StatusOngoing
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