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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2018-003682-34
    Sponsor's Protocol Code Number:VKTX01
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-03-22
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2018-003682-34
    A.3Full title of the trial
    A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients
    Pivotní klinická studie fáze 3 pro hodnocení bezpečnosti a účinnosti přípravku clazakizumab při léčbě chronické aktivními protilátkami zprostředkované rejekce u příjemců transplantované ledviny.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to measure how safe and successful Clazakizumab is in preventing kidney transplant rejection
    A.4.1Sponsor's protocol code numberVKTX01
    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 SponsorVitaeris Inc.
    B.1.3.4CountryCanada
    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 supportVitaeris Inc.
    B.4.2CountryCanada
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVitaeris Inc.
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address1500 – 355 Burrard Street
    B.5.3.2Town/ cityVancouver, BC,
    B.5.3.3Post codeV6C 2G8
    B.5.3.4CountryCanada
    B.5.5Fax number+1604-608-3822
    B.5.6E-mailregulatory@vitaerisbio.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 nameClazakizumab 12.5 mg/mL
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCLAZAKIZUMAB
    D.3.9.1CAS number 1236278-28-6
    D.3.9.3Other descriptive nameCLAZAKIZUMAB
    D.3.9.4EV Substance CodeSUB117542
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number12.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Active Antibody-Mediated Rejection (CABMR) in Kidney Transplant Recipients
    E.1.1.1Medical condition in easily understood language
    Kidney rejection after transplant cause by specific antibodies. This needs to be established in blood and biopsy investigations.
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To evaluate the efficacy of clazakizumab in preventing all-cause composite allograft loss due to CABMR (defined as return to dialysis, allograft nephrectomy, re-transplantation, estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m^2 or death from any cause) (Final Analysis).
    2. To evaluate the efficacy of clazakizumab in slowing/preventing the progressive loss of kidney function (as measured by eGFR using the Modification of Diet in Renal Disease 4 (MDRD4) equation) (Interim Analysis #2 (IA #2)).
    3. To evaluate the safety of clazakizumab.
    E.2.2Secondary objectives of the trial
    1. To evaluate the effects of clazakizumab on death-censored allograft loss (defined as return to dialysis, allograft nephrectomy, re-transplantation or eGFR <15 mL/min/1.73 m^2 but excluding death from any cause).
    2. To evaluate the effects of clazakizumab on albuminuria.
    3. To evaluate the effects of clazakizumab on DSA titers and mean fluorescence intensity (MFI) scores.
    4. To evaluate the effects of clazakizumab on incidence of acute rejection episodes (TCMR and ABMR).
    5. To evaluate the effects of clazakizumab on the histology of kidney biopsies according to the Banff 2015 lesion grading scores.
    6. To evaluate the effects of clazakizumab on overall patient survival.
    7. To evaluate the effects of clazakizumab on healthcare utilization due to ABMR and patient reported outcomes including health-related quality of life (HRQoL).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18-70 years.
    2. Living donor/deceased donor kidney transplant recipients ≥6 months from time of transplant.
    3. Diagnosis of CABMR (according to Banff 2015 diagnostic criteria) to include all of the following:
    • Biopsy-proven CABMR (i.e., chronic glomerulopathy (cg) >0) with/without C4d staining. Repeat biopsy to be performed if previous biopsy is not within 6 months (+3 weeks) of the start of the screening period. The local pathologist’s diagnosis will be reviewed by a central pathologist to confirm eligibility for entry into the study. Subjects without evidence of chronic tissue injury on light microscopy but who have glomerular basement membrane double contours on electron microscopy (cg1a) are eligible.
    • Positive for human leukocyte antigen (HLA) DSA (using single-antigen bead-based assays) post-transplant. Local laboratory DSA results will be reviewed by the central HLA reviewer to confirm eligibility for entry into the study. If presence of HLA DSA is confirmed within 6 months (+3 weeks) of the start of the screening period, the test does not need to be repeated for eligibility.
    • Note: Treatments for ABMR (including CABMR) or TCMR are not allowed within 3 months of the start of screening (see Exclusion Criterion 3). If a subject has received one of these treatments at any time prior, a repeat biopsy and repeat DSA test must be performed after halting / completing treatment (to show continuing CABMR). At least 2 months ± 2 weeks should elapse from the end of treatment before the repeat biopsy and DSA test can be performed.
    4. Written informed consent obtained from subject (or legally acceptable representative) before any trial-related procedures.
    E.4Principal exclusion criteria
    1. Participant is unable or unwilling to comply with study procedures in the opinion of the Investigator.
    2. Multi-organ transplant recipient or cell transplant (islet, bone marrow, stem cell) recipient. Note: recipients of multiple previous kidney transplants are allowed.
    3. Treatment for ABMR (including CABMR) or TCMR within 3 months of the start of screening.
    4. Received T cell depleting agents (e.g., alemtuzumab, anti-thymocyte globulin) within 3 months of the start of screening.
    5. Treatment with mTOR inhibitors within 4 weeks of the start of screening.
    6. Biopsy showing pure TCMR or advanced interstitial fibrosis (ci3), advanced tubular atrophy (ct3), vascular fibrous intimal thickening (cv3) or other significant causes of renal dysfunction (e.g., BK virus (BKV) nephropathy, glomerulonephritis).
    7. Impaired renal function due to disorders in the transplanted allograft (e.g., renal artery stenosis, hydronephrosis).
    8. eGFR <25 mL/min/1.73 m^2 or >65 mL/min/1.73 m^2 (MDRD4).
    9. Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (UACR) ≥2,200 mg/g (≥220 mg/mmol). If spot UACR is above defined limits, repeat test on separate day to confirm ineligibility (or collect 24-hour urine to confirm nephrotic range proteinuria (≥3.0 g/day)).
    10. Pregnant, breastfeeding, or unwillingness to practice adequate contraception (i.e., a highly effective or acceptable method of contraception) during the study and for 5 months after last dose of investigational drug.
    11. History of anaphylaxis or known hypersensitivity to clazakizumab or to any constituent of the drug product.
    12. Abnormal liver function tests (LFTs) (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin >1.5 x upper limit of normal) or other significant liver disease.
    13. History of active tuberculosis (TB).
    14. History of latent TB (e.g., positive QuantiFERON-TB test) without history of active TB unless subject has completed a full course of prophylactic treatment.
    15. History of human immunodeficiency virus (HIV) infection or positive for HIV.
    16. Seropositive for hepatitis B surface antigen (HBsAg).
    17. Hepatitis C virus (HCV) RNA positive.
    18. Known Epstein-Barr virus (EBV) mismatch (at time of transplant): donor seropositive, recipient seronegative.
    19. History of gastrointestinal perforation; diverticular disease or divertikulitis (except if disease has been fully excised); or inflammatory bowel disease (except fully excised ulcerative colitis).
    20. Neutropenia (<1,000/mm^3) or thrombocytopenia (<50,000/mm^3).
    21. Active infections requiring systemic antimicrobial agents and unresolved prior to screening.
    22. History of or current invasive fungal infection or other opportunistic infection, including (but not limited to) the following: a nontuberculous mycobacterial infection, aspergillosis, pneumocystosis, and toxoplasmosis.
    23. Active viral infections such as BKV, CMV, or EBV based on polymerase chain reaction (PCR) testing. Active infection is defined as a test result ≥ lower limit of quantification (LLOQ).
    24. Current or recent (within 3 months) participation in an interventional trial.
    25. Administration of a live vaccine within 6 weeks of the start of screening, including but not limited to the following:
    • Adenovirus
    • Measles, mumps, and rubella
    • Oral polio
    • Oral typhoid
    • Rotavirus
    • Varicella zoster
    • Yellow fever
    26. History of alcohol or illicit substance (including marijuana) abuse.
    27. Present or previous (within 3 years) malignancy except for basal cell carcinoma, fully excised squamous cell carcinoma of the skin, or non-recurrent (within 5 years) cervical carcinoma in-situ.
    28. Presence of a condition or abnormality (i.e., clinically significant endocrine, autoimmune, metabolic, neurological, psychiatric/psychological, renal, gastrointestinal, hepatic, and hematological or any other system abnormalities that are uncontrolled with standard treatment) that in the opinion of the Investigator would compromise the safety or life expectancy of the patient or the quality of the data.
    29. History of intolerance to trimethoprim and/or sulfamethoxazole. This criterion does not apply if subject is already taking another suitable Investigator-approved alternative for Pneumocystis jiroveci pneumonia (PJP) prophylaxis, or if subject is willing to begin taking an Investigator-approved alternative prophylactic therapy at least 1 week prior to the Day 1 Baseline visit (Visit 2).
    30. Prior exposure to clazakizumab, TCZ, or other IL-6/IL-6R blockers.
    31. ABO-incompatible transplant recipient.
    32. Severe hypogammaglobulinemia (defined as immunoglobulin G (IgG) <400 mg/dL).
    33. Prior (within 2 years of the start of screening) exposure to proteasome inhibitors (e.g., bortezomib).
    34. Active infection with COVID-19.
    E.5 End points
    E.5.1Primary end point(s)
    Final Analysis Primary Endpoint:
    • Time to all-cause composite allograft loss (defined as return to dialysis, allograft nephrectomy, re-transplantation, eGFR <15 mL/min/1.73 m^2 or death from any cause (including death with functioning allograft)). An eGFR <15 mL/min/1.73 m^2 must be confirmed by a repeat measurement taken between 14 to 30 days later. Temporary return to dialysis due to acute kidney injury (AKI) and temporary eGFR decline to <15 mL/min/1.73 m^2 due to AKI are both excluded.

    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary efficacy endpoint will be analyzed as part of the final analysis when approximately 221 all-cause allograft loss events have occurred.
    E.5.2Secondary end point(s)
    • Incidence and time to death-censored allograft loss.
    • Change in mean eGFR from Baseline to End of Study (EOS).
    • Change in spot UACR from Baseline to EOS.
    • Change in DSA titers and MFI scores from Baseline to EOS.
    • Incidence of acute rejection episodes (TCMR and ABMR) from Baseline to EOS.
    • Change in Banff lesion grading score (2015 criteria) of pre-treatment to post treatment (Week 52) kidney biopsies.
    • Overall patient survival.
    • Healthcare utilization associated with the treatment of ABMR to Week 52 as well as to EOS.
    • Change in patient reported outcomes (including HRQoL) from Baseline to Week 52 as well as to EOS, using multiple tools.

    E.5.2.1Timepoint(s) of evaluation of this end point
    From Baseline to Week 52 and / or End of Study (EOS) as detailed above
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic 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) 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 No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the 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 concerned1
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA29
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Canada
    Czech Republic
    France
    Germany
    Hungary
    Netherlands
    Spain
    Switzerland
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months10
    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: 310
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 350
    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)
    The post-trial treatment will be performed by the trial investigator and/or the patient’s non-trial physician based on guidance from the trial investigator as applicable. This could also involve further treatment with Interleukin-6 inhibitors, if required.
    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 Decision2019-10-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-19
    P. End of Trial
    P.End of Trial StatusCompleted
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