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    Summary
    EudraCT Number:2016-001121-14
    Sponsor's Protocol Code Number:CL010_168
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-01-07
    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 number2016-001121-14
    A.3Full title of the trial
    Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of CCX168 (Avacopan) in Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis Treated Concomitantly with Rituximab or Cyclophosphamide/Azathioprine
    Studio di Fase 3, randomizzato, in doppio cieco, controllato verso placebo per valutare la sicurezza e l¿efficacia di CCX168 (Avacopan) in pazienti con vasculite associata ad anticorpi citoplasmatici antineutrofili (ANCA) in associazione con rituximab o ciclofosfamide/azatioprina
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Trial to Evaluate the Safety and Efficacy of CCX168 (Avacopan), a new drug for the treatment of Vasculitis of a certain type, called ANCAAssociated Vasculitis (AAV).
    Studio clinic per valutare la sicurezza e l'efficacia di CCX168 (Avacopan), un nuovo farmaco per il trattamento di un particolare tipo di vasculite, chiamata Vasculite ANCA associate (AAV).
    A.4.1Sponsor's protocol code numberCL010_168
    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 SponsorCHEMOCENTRYX, 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 supportChemoCentryx, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationChemoCentryx, Inc.
    B.5.2Functional name of contact pointAntonia Potarca
    B.5.3 Address:
    B.5.3.1Street Address850 Maude Avenue
    B.5.3.2Town/ cityMountain View, CA
    B.5.3.3Post code94043
    B.5.3.4CountryUnited States
    B.5.4Telephone number0031630892290
    B.5.5Fax number0016502102910
    B.5.6E-mailapotarca@chemocentryx.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 Yes
    D.2.5.1Orphan drug designation numberMPA - EMA/OD/149/14, GPA -EMA/OD/150/14
    D.3 Description of the IMP
    D.3.1Product nameAvacopan
    D.3.2Product code CCX168
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAvacopan
    D.3.9.1CAS number 1346623-17-3
    D.3.9.2Current sponsor codeCCX168
    D.3.9.4EV Substance CodeSUB31899
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Prednison acis¿ 5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderacis Arzneimittel GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 namePrednisone
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codePrednisone
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Prednison acis¿ 20 mg
    D.2.1.1.2Name of the Marketing Authorisation holderacis Arzneimittel GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 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 placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
    Vasculite associata ad anticorpi citoplasmatici anti neutrofili (ANCA)
    E.1.1.1Medical condition in easily understood language
    Vasculitis (a disorder that destroys blood vessels by inflammation) of a certain kind, called ANCA-associated vasculitis
    Vasculite (una malattia che distrugge I vasi sanguigni tramite l'infiammazione) di un determinate tipo, chiamata vasculite associata ad ANCA
    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 10063344
    E.1.2Term Microscopic polyangiitis
    E.1.2System Organ Class 10047065 - Vascular disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10050894
    E.1.2Term Anti-neutrophil cytoplasmic antibody positive vasculitis
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10072579
    E.1.2Term Granulomatosis with polyangiitis
    E.1.2System Organ Class 10047065 - Vascular disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain remission in patients with active anti-neutrophil
    cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab
    L¿obiettivo primario consiste nel valutare l¿efficacia di CCX168 (avacopan) per indurre e mantenere la remissione nei pazienti con vasculite associata ad anticorpi citoplasmatici antineutrofili (Anti-Neutrophil Cytoplasmic Antibody, ANCA)
    ((ANCA)-Associated Vasculitis, AAV) attiva, quando utilizzato in combinazione con ciclofosfamide seguita da azatioprina, o in combinazione con rituximab.
    E.2.2Secondary objectives of the trial
    1. Evaluation of the glucocorticoid-induced toxicity compared between test and control group
    2. Evaluation of rapidity of response compared between test and control group
    3. Evaluation of the safety compared between test and control group
    4. Assessment of health-related quality-of-life changes compared between test and control group
    5. Assessment of changes in parameters of renal disease compared between test and control group
    6. Assessment of changes in cumulative organ damage compared between test and control group
    7. Assessment of changes in markers of pharmacodynamics in plasma and urine compared between test and control group
    8. Evaluation of the pharmacokinetic profile of CCX168 in patients with AAV.
    1. Valutazione della tossicit¿ indotta da glucocorticoidi nel gruppo sperimentale rispetto al gruppo di controllo
    2. Valutazione della rapidit¿ di risposta nel gruppo sperimentale rispetto al gruppo di controllo
    3. Valutazione della sicurezza nel gruppo sperimentale rispetto al gruppo di controllo
    4. Valutazione delle variazioni della qualit¿ della vita nel gruppo sperimentale rispetto al gruppo di controllo
    5. Valutazione delle variazioni dei parametri della malattia renale nel gruppo sperimentale rispetto al gruppo di controllo
    6. Valutazione delle variazioni del danno cumulativo agli organi nel gruppo sperimentale rispetto al gruppo di controllo
    7. Valutazione delle variazioni dei marcatori di farmacodinamica nel plasma e nelle urine nel gruppo sperimentale rispetto al gruppo di controllo
    8. Valutazione del profilo farmacocinetico di CCX168 in pazienti con AAV.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis, consistent with Chapel-Hill Consensus
    Conference definitions
    2. Aged at least 18 years, with newly-diagnosed or relapsed AAV where treatment with cyclophosphamide or rituximab is needed; where
    approved, adolescents (12-17 year old) may be enrolled
    3. Positive test for anti-PR3 or anti-MPO (current or historic) antibodies
    4. At least one major item, or at least 3 minor items, or at least the 2 renal items of proteinuria and hematuria in the BVAS
    5. Estimated glomerular filtration rate =15 mL/minute/1.73 m2 (using the MDRD method) at screening
    6. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; written Informed Consent should
    be obtained from the legal guardian in accordance with regional laws or regulations for patients 12 to 17 years of age
    7. Judged by the Investigator to be fit for the study, based on medical history, physical examination (including electrocardiogram [ECG]), and
    clinical laboratory assessments.
    1. Diagnosi clinica di granulomatosi con poliangioite (di Wegener) o poliangioite microscopica, coerente con le definizioni della Chapel-Hill Consensus Conference
    2. Avere almeno 18 anni, con AAV di nuova diagnosi o recidivata dove sia necessario il
    trattamento con ciclofosfamide o rituximab; dove approvato, gli adolescenti (12-17 anni di
    età) possono essere arruolati
    3. Test positivo per anticorpi anti-PR3 o anti-MPO (attuale o storico);
    4. Almeno un evento maggiore, o almeno 3 eventi minori, o almeno i 2 eventi renali di
    proteinuria ed ematuria nel BVAS
    5. Velocità di filtrazione glomerulare stimata = 15 ml/minuto/1,73 m2 (utilizzando il metodo
    MDRD) allo screening
    6. Essere disposti e in grado di fornire il consenso informato scritto e rispettare i requisiti del
    protocollo dello studio; il consenso informato scritto deve essere ottenuto dal tutore legale
    in conformità alle normative o alle leggi regionali per i pazienti di età compresa tra 12 e 17
    anni, e
    7. Essere secondo lo sperimentatore altrimenti adatti allo studio, sulla base dell’anamnesi,
    dell’esame obiettivo (incluso l’elettrocardiogramma [ECG]) e delle valutazioni cliniche di
    laboratorio.
    E.4Principal exclusion criteria
    1. Pregnant or breast-feeding
    2. Alveolar hemorrhage requiring invasive pulmonary ventilation support
    anticipated to last beyond the screening period of the study
    3. Any other known multi-system autoimmune disease including eosinophilic granulomatosis with polyangiitis (Churg-Strauss), systemic
    lupus erythematosus, IgA vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjögren's syndrome, anti-glomerular basement membrane
    disease, or cryoglobulinemic vasculitis
    4. Required dialysis or plasma exchange within 12 weeks prior to screening
    5. Have had a kidney transplant
    6. Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil, or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the
    cyclophosphamide or rituximab dose on Day 1
    7. Received intravenous glucocorticoids, >3000 mg methylprednisolone equivalent, within 4 weeks prior to screening
    8. Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior
    to the screening visit
    9. Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e., CD19 count > 0.01x109/L); received anti-TNF treatment, abatacept, alemtuzumab, IVIg, belimumab, tocilizumab, or eculizumab within 12 weeks prior to screening
    10. Currently taking a strong inducer of the cytochrome P450 3A4 (CYP3A4) enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John's wort
    11. Any of the following within 12 weeks prior to screening: symptomatic congestive heart failure requiring prescription medication, unstable angina (unless successfully treated with stent or bypass surgery), clinically significant cardiac arrhythmia, myocardial infarction or stroke
    12. History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis

    1. Gravidanza o allattamento;
    2. Emorragia alveolare che richieda una ventilazione polmonare di supporto invasiva che si
    prevede possa protrarsi oltre il periodo di screening dello studio;
    3. Qualsiasi altra malattia autoimmunitaria multi-sistema nota inclusi la granulomatosi
    eosinofila con poliangioite (Churg-Strauss), il lupus eritematoso sistemico, la vasculite da
    IgA (Henoch-Schönlein), la vasculite reumatoide, la sindrome di Sjögren, la malattia della
    membrana basale glomerulare o la vasculite crioglobulinemica;
    4. Dialisi o plasmaferesi effettuata entro 12 settimane prima dello screening
    5. Essere stati sottoposti a un trapianto di rene
    6. Avere ricevuto ciclofosfamide entro 12 settimane prima dello screening; se si sta assumendo
    azatioprina, micofenolato mofetile o metotrexato al momento dello screening, questi farmaci devono essere interrotti prima di ricevere la dose di ciclofosfamide o rituximab il Giorno 1;
    7. Avere ricevuto glucocorticoidi per via endovenosa, ad una dose equivalente a > 3000 mg di metilprednisolone, entro 4 settimane prima dello screening;
    8. Avere preso una dose giornaliera per via orale di un glucocorticoide equivalente a più di 10 mg di prednisone per più di 6 settimane continuamente prima della visita di screening;
    9. Avere ricevuto rituximab o altro anticorpo delle cellule B entro 52 settimane dallo screening
    o 26 settimane purché abbia avuto luogo la ricostituzione delle cellule B (ossia, conta di
    CD19 > 0,01 x 10 9/L); aver ricevuto un trattamento anti-TNF, abatacept, alemtuzumab,
    IVIg, belimumab, tocilizumab o eculizumab entro 12 settimane prima dello screening
    10. Attualmente si sta prendendo un forte induttore dell’enzima citocromo P450 3A4 (CYP3A4), come carbamazepina, fenobarbital, fenitoina, rifampicina, o iperico;
    11. Uno qualsiasi dei seguenti eventi entro 12 settimane prima dello screening: insufficienza
    cardiaca congestizia sintomatica che necessiti di un farmaco da prescrizione, angina instabile (a meno che non sia stata trattata con successo con stent o intervento di bypass), aritmia cardiaca clinicamente significativa, infarto miocardico o ictus
    12. Storia o presenza di qualsiasi forma di tumore entro 5 anni prima dello screening, con eccezione del carcinoma della pelle a cellule basali o a cellule squamose escisso o carcinoma in situ come carcinoma cervicale o mammario in situ che sia stato escisso o resecato completamente e non presenti evidenza di metastasi o ricorrenza locale
    E.5 End points
    E.5.1Primary end point(s)
    1. The proportion of patients achieving disease remission at Week 26, defined as a BVAS of 0 and not taking glucocorticoids within 4 weeks
    prior to Week 26.
    2. The proportion of patients achieving sustained disease remission, defined as remission at Week 26 without relapse to Week 52 (BVAS of 0 and not taking glucocorticoids within 4 weeks prior to Week 52).
    1. La proporzione dei pazienti che raggiungo la remissione alla settimana 26, definite come BVAS 0 e che non prendono glucocorticoidi nelle 4 settimane precedent la settimana 26
    2. La proporzione dei pazienti che raggiungono una remissione duratura della malattia, definite come remissione alla settimana 26 senza recidiva alla settimana 52 (BVAS 0 e che non prendono glucocorticidi nelle 4 settimane precedent la settimana 52)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Both endpoints will be assessed after 52 weeks of treatment
    Entrambi gli End point verranno valutati dopo 52 settimane di trattamento
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints include:
    1. Glucocorticoid-induced toxicity as measured by change from baseline over the first 26 weeks in the glucocorticoid toxicity index;
    2. Early remission, defined as BVAS of 0 at Week 4;
    3. Change from baseline over 52 weeks in health-related quality-of-life as measured by the domains and component scores of the SF-36 v2 and
    EQ-5D-5L VAS and index;
    4. Proportion of patients and time to experiencing a relapse after previously achieving remission in the study; relapse is defined as occurrence of at least one major item in the BVAS, or three or more
    minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after having achieved remission (BVAS = 0) in
    the study;
    5. In patients with renal disease at baseline (based in the BVAS renal component), the change in eGFR from baseline over 52 weeks;
    6. In patients with renal disease at baseline (based in the BVAS renal component), the percent change in UACR from baseline over 52 weeks;
    7. In patients with renal disease at baseline (based in the BVAS renal component), the percent change in urinary MCP-1:creatinine ratio from baseline over 52 weeks;
    8. Change in the VDI from baseline over 52 weeks.

    Safety endpoints, other than glucocorticoid-induced toxicity listed under the efficacy endpoints, include:
    1. Patient incidence of treatment-emergent serious adverse events, adverse events, and withdrawals due to adverse events;
    2. Change from baseline and shifts from baseline in all safety laboratory parameters;
    3. Change from baseline in vital signs, and
    4. Incidence of clinically significant ECG changes from baseline.

    PK endpoint:
    CCX168 (and metabolite) plasma concentration results will be used to calculate trough plasma concentrations (Cmin) over the course of the clinical trial.

    PD endpoints:
    The following PD endpoints may be assessed:
    1. Change and percent change from baseline in plasma biomarkers such as cystatin C, complement fragments, inflammatory chemokine and cytokine levels.
    2. Change and percent change from baseline in urine biomarkers such as renal injury and inflammation markers (e.g., KIM-1 and NGAL), soluble CD163, complement fragments, inflammatory chemokine and cytokine levels;
    3. Change from baseline in CBC count (especially WBCs, neutrophils, and lymphocytes) and lymphocyte subset counts including B cells, T cells, and natural killer cells;
    4. Change from baseline in blood cell gene expressions such as neutrophil functional status markers.
    End point secondary di efficacia includono:
    1. Valutazione della tossicit¿ dei glucocorticoidi misurato come cambiamento dal basale durante le prime 26 settimane tramite l'indice di tossicit¿ dei glucocorticoidi
    2. Remissione precoce, definita come BVAS 0 alla settimana 4
    3. Cambiamenti rispetto al basale della qualit¿ della vita e della salute durante le 52 settimane misurato come I domini e I risultati dei componenti degli indici SF-36- V2 e EQ-5D-5L VAS
    4. Proporzione dei pazienti e tempo impiegato perch¿ si verifichi una ricaduta dopo precedente remissione durante lo studio; la ricaduta viene definite come ricorrenza di almeno evento maggiore nel BVAS, oppure 3 o pi¿ eventi minori nel BVAS, oppure 1 o 2 eventi minori nel BVAS registrati a due visite consecutive dopo aver raggiunto la remissione (BVAS=0) durante lo studio
    5. Il cambiamento in eGFR dal basale durante le 52 settimane in pazienti con malattia renale allo screening (basato sula componente renale del BVAS)
    6. Il cambio percentuale nel UACR dallo screening per 52 settimane in pazienti con malattia renale allo screening (basato sulla componente renale del BVAS)
    7. Il cambio percentuale nel rapport MCP-1:Creatinina urinaria dallo screening alla settimana 52 in pazienti con malattia renale allo screening (basato sulal componente renale del BVAS)
    8. Cambio nel VDI dallo screening fino alla setimana 52

    End point di sicurezza, oltre che la tossicit¿ indotta dai glucocorticoidi, includono:

    1. Incidenza di SAE dovuti al trattamento, AE, e ritiri dovuti ad eventi avversi
    2. Cambiamenti dallo screening di tutti I parametri di sicurezza valutati tramite test di laboratorio
    3. Cambiamenti dal basale nei segni vitali e
    4. Incidenza di cambiamenti significativi nelle ECG dallo screening

    End point di Farmacocinetica
    I risultati della concentrazione plasmatica di CCX168 (e dei suoi metaboliti) verranno usati per calcolare la concentrazione minima nel plasma durante lo studio

    End point di Farmacodinamica
    I seguenti end pint di PD verranno valutati:
    1. Cambiamento e percentuale nei biomarcatori presenti nel plasma come Cistatina C, frammenti del complemento, chemochine infiammatorie e citochine
    2. Cambiamento e relative percentuale dallo screening nei biomarcatori dell'urina come I marcatori di infiammazione e danno renale (e.g. KIM-1 e NGAL), Cd163 solubile, frammenti del complemento, chemochine e citochine infiammatorie
    3. Cambiamenti dallo screening nella conta delle CBC (in particolare WBC, neutrofili e linfociti) e sottopopolazioni linfocitarie incluse cellule B, e natural killer
    4. Cambiamenti r ispetto allo screening nell'espressione genica delle cellule del sangue come I marcatori funsionali dei neutrofili
    E.5.2.1Timepoint(s) of evaluation of this end point
    various, refer to information in E.5.2
    Vari, fare riferimento alle informazioni nella sezione E.5.2
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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) Yes
    E.8.2.2Placebo No
    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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA106
    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
    Australia
    Austria
    Belgium
    Canada
    Czechia
    Denmark
    France
    Germany
    Hungary
    Ireland
    Italy
    Netherlands
    New Zealand
    Spain
    Sweden
    Switzerland
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LPLV
    LPLV
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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 Yes
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 10
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 240
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Adolescents
    Adolescenti
    F.4 Planned number of subjects to be included
    F.4.1In the member state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 300
    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 - expected normal treatment of that condition
    Nessuno - trattamento normale per la malattia in esame
    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 Decision2017-05-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-04-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-11-01
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