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    Summary
    EudraCT Number:2018-001003-36
    Sponsor's Protocol Code Number:KPL-301-C001
    National Competent Authority:Slovenia - JAZMP
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-08-30
    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 ConcernedSlovenia - JAZMP
    A.2EudraCT number2018-001003-36
    A.3Full title of the trial
    A Phase 2, randomized, double-blind placebo-controlled study to test the efficacy and safety of KPL-301 in giant cell arteritis
    Randomizirana, dvojno slepa, s placebom nadzorovana študija 2. faze za preverjanje učinkovitosti in varnosti KPL-301 pri arteritisu celic velikank
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study to test treatment of KPL-301 compared to placebo in giant cell arteritis
    A.4.1Sponsor's protocol code numberKPL-301-C001
    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 SponsorKiniksa Pharmaceuticals, Ltd. (Hamilton, Bermuda) c/o Kiniksa Pharmaceuticals Corp.
    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 supportKiniksa Pharmaceuticals Corp.
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportKiniksa Pharmaceuticals, Ltd.
    B.4.2CountryBermuda
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKiniksa Pharmaceuticals, Ltd. (Hamilton, Bermuda) c/o Kiniksa Pharmaceuticals Corp.
    B.5.2Functional name of contact pointKiniksa Medical Information Group
    B.5.3 Address:
    B.5.3.1Street Address100 Hayden Ave
    B.5.3.2Town/ cityLexington, Massachusetts
    B.5.3.3Post code02421
    B.5.3.4CountryUnited States
    B.5.4Telephone number17814319100
    B.5.5Fax number18885227408
    B.5.6E-mailstudyinfo@kiniksa.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 nameMavrilimumab
    D.3.2Product code KPL-301
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    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 INNMAVRILIMUMAB
    D.3.9.1CAS number 1085337-57-0
    D.3.9.2Current sponsor codeKPL-301
    D.3.9.3Other descriptive namen/a
    D.3.9.4EV Substance CodeSUB189175
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Prednisone Tablets, USP
    D.2.1.1.2Name of the Marketing Authorisation holderPar Pharmaceutical
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 Tablets, USP
    D.3.2Product code N/A
    D.3.4Pharmaceutical form Tablet
    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 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 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 placeboSolution for injection in pre-filled syringe
    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
    giant cell arteritis
    E.1.1.1Medical condition in easily understood language
    an inflammatory disease of blood vessels
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10018250
    E.1.2Term Giant cell arteritis
    E.1.2System Organ Class 100000004866
    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 of the study is to evaluate the efficacy of KPL-301 versus placebo, coadministered with a 26-week steroid taper, for maintaining sustained remission for 26 weeks in subjects with newonset or relapsing/refractory giant cell arteritis (GCA).
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study, in subjects with new-onset and relapsing/refractory GCA, are:
    a) To evaluate the effect of KPL-301 vs placebo on cumulative corticosteroid dose.
    b) To evaluate the effect of KPL-301 vs placebo on health-related quality of life (HRQoL).
    c) To evaluate the safety and tolerability of KPL-301.
    d) To evaluate the pharmacokinetics (PK) of KPL-301.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able and willing to provide written informed consent and to comply
    with the study protocol
    2. Age of ≥ 50 to 85 inclusive
    3. Diagnosis of new-onset or relapsing GCA classified according to the
    following criteria:
    New-onset: Initial diagnosis of GCA within 6 weeks of Day 0, defined as:
    a) Westergren ESR > 30 mm/hour or CRP ≥ 1 mg/dL
    b) AND at least one of the following:
    i. Unequivocal cranial symptoms of GCA (new-onset localized headache,
    scalp or temporal artery pain or tenderness, ischemia-related vision loss,
    or otherwise unexplained mouth or jaw pain upon mastication)
    ii. Unequivocal extracranial symptoms of GCA such as claudication of the
    extremities
    iii. Symptoms of PMR, defined as shoulder and/or hip girdle pain
    associated with inflammatory morning stiffness
    c) AND at least one of the following:
    i. TAB or ultrasound revealing features of GCA
    ii. Evidence of large-vessel vasculitis by angiography or cross-sectional
    imaging study such as MRI, CT/CTA, or PET-CT of the aorta or other
    great vessels
    Relapsing: Diagnosis of GCA > 6 weeks before Day 0 AND:
    Active GCA within 6 weeks of Day 0 defined as clinical sign/symptom(s)
    as per above and Westergren ESR> 30 mm/hour or CRP ≥ 1 mg/ dL
    Refractory nonremitting: Diagnosis of GCA > 6 weeks before Day 0 AND
    No remission since the diagnosis of disease as per clinical expectations.
    i.e. Presence of sign/symptoms as per above and Westergren
    ESR>30mm/hour or CRP ≥ 1 mg/ dL within 6 weeks of Day 0
    4. Remission of GCA at or before Day 0 (resolution of GCA symptom(s)
    and CRP < 1.0 mg/dL or ESR < 20 mm in the first hour), such that the
    subject can safely participate in the study and follow the protocol
    defined procedures, including initiation of the prednisone taper at the
    protocol-specified starting dose (i.e., ≤60 mg/day)
    5. At Day 0, receiving or able to receive oral prednisone up to 60 mg/day
    for the treatment of GCA
    6. If using methotrexate (MTX), oral or parenteral up to 25mg/week is
    permitted in screening if started more than 6 weeks prior to Day 0 and
    should be tapered to zero by Day 0.
    7. Willing to receive antiplatelet therapy depending on the Investigator's
    decision
    8. Willing to receive treatment for prevention of corticosteroid-induced
    osteopenia/osteoporosis depending on the Investigator's decision
    9. Female subjects must be:
    a) postmenopausal, defined as at least 12 months post cessation of
    menses (without an alternative medical cause), or
    b) permanently sterile following documented hysterectomy, bilateral
    salpingectomy, bilateral ophorectomy, or tubal ligation or having a male
    partner with vasectomy as affirmed by the subject, or
    c) nonpregnant, nonlactating, and if sexually active having agreed to use
    a highly effective method of contraception (i.e., hormonal contraceptives
    associated with inhibition of ovulation or intrauterine device [IUD], or
    intrauterine hormone-releasing system [IUS], or sexual abstinence)
    from Screening visit until the final Washout Safety Follow-up visit 84 ± 3
    days from EOT Visit.
    10. Male subjects must have documented vasectomy or if sexually active
    must agree to use a highly effective method of contraception with their
    partners of childbearing potential (i.e., hormonal contraceptives
    associated with the inhibition of ovulation or intrauterine device [IUD],
    or intrauterine hormone-releasing system [IUS], or sexual abstinence)
    from Day 0 until the final Washout Safety Follow-up visit 84± 3 days
    from EOT Visit. Male subjects must agree to refrain from donating sperm
    during this time period.
    E.4Principal exclusion criteria
    General Exclusion Criteria
    1. Major surgery within 8 weeks prior to Screening or planned major
    surgery within 12 months after randomization
    2. Transplanted organs (except corneal transplant performed more than
    3 months prior to randomization)
    3. Major ischemic event unrelated to GCA within 12 weeks of Screening
    Exclusions Related to Prior or Concomitant Therapy
    4. Concurrent enrollment in another clinical study, with the exception of
    observational studies
    5. Previous treatment with KPL-301
    6. Treatment with any non-biologic investigational drug therapy within 4
    weeks or 5 half-lives of the study agent, whichever was longer, prior to
    Screening
    7. Any cell-depleting biological therapies (e.g., anti-CD20) within 12
    months prior to Day 0; or previous treatment with noncell-depleting
    biological therapies (such as anti-tumor necrosis factor [TNF], anakinra,
    anti-Interleukin [IL]-6 receptor [e.g. tocilizumab], or abatacept) within
    8 weeks (or 5 half-lives, whichever is longer) prior to Screening
    8. Treatment with alkylating agents within 12 weeks prior to Screening
    9. Intramuscular, IV corticosteroids, Intra-articular corticosteroids
    within 4 weeks prior to Screening
    10. Receipt of live (attenuated) vaccine within the 4 weeks before Day 0
    11. Treatment with hydroxychloroquine, cyclosporine A, azathioprine,
    cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks of
    Screening Relating to Medical History
    12. Female subjects who are pregnant, intending to become pregnant, or
    are breastfeeding
    13. Any condition that, in the opinion of the Investigator, could interfere
    with evaluation of KPL-301 or interpretation of subject safety or
    confound the results of the study
    14. Known history of allergy or reaction to any component of the KPL-
    301 or placebo formulation or to any other biologic therapy or
    prednisone or any of its excipients
    15. Positive (or 2 indeterminate) QuantiFERON test results.
    16. Clinically significant active infection including signs/symptoms
    suggestive of infection, any significant recurrent or chronic infection
    (including positive hepatitis C virus antibody [HCVAb]), or any episode
    of infection requiring hospitalization or treatment with IV antibiotics
    within 12 weeks before Screening. Subjects with any opportunistic
    infection within 6 months before Screening will be excluded from the
    study.
    17. Subjects with chronic active hepatitis B infection as defined below
    will be excluded from the study:
     Hepatitis B surface antigen (HbsAg) positive
     Hepatitis B anti-core antibody positive but anti-surface antibody
    negative
    18. Subjects at a high risk of infection (e.g., history of hereditary or
    acquired immune deficiency disorder including a history of known
    human immunodeficiency virus [HIV] infection), a history of an infected
    joint prosthesis at any time with that prosthesis still in situ, leg ulcers,
    indwelling urinary catheter, or persistent or recurrent chest infections
    19. History of cancer within the last 10 years - except for basal and
    squamous cell carcinoma of the skin or in situ carcinoma of the cervix
    treated and considered cured
    20. Evidence of clinically uncontrolled respiratory disease. The
    Investigator should review the data from subjects' respiratory
    assessments including chest x-ray and pulmonary function tests (PFTs)
    including DLCO performed during the screening period or within 12
    weeks prior to Day 0 if results of prior assessments are available.
    Available PFT and DLCO assessments must have had values ≥ 60% of
    predicted for measurements performed and no uncontrolled lung
    disease. A subject's medical regimen should not have been significantly
    intensified to control lung disease within 12 weeks prior to Day 0.
    21. History of chronic respiratory tract infections
    22. Congestive heart failure of New York Heart Association classification
    III or IV
    23. At screening blood tests, any of the following:
    a) Aspartate transaminase (AST) > 2 × upper limit of normal (ULN)
    b) Alanine transaminase (ALT) > 2 × ULN
    c) Hemoglobin < 75 g/L
    d) Neutrophils < 1.5 × 109/L
    e) Creatinine clearance (CrCl) <30 mL/min
    E.5 End points
    E.5.1Primary end point(s)
    Time to flare by week 26 defined as time from randomization to the first
    flare occurring within the treatment period
    E.5.1.1Timepoint(s) of evaluation of this end point
    Appro. 32 weeks after the start of the study
    E.5.2Secondary end point(s)
    • Sustained remission rate at Week 26
    • Percentage of subjects who have completed the corticosteroid taper and who have a normal ESR by week 26
    • Percentage of subjects who have completed the corticosteroid taper and who have a normal CRP by Week 26
    • Percentage of subjects who completed the corticosteroid taper and who have no signs/symptoms of GCA nor new or worsening vasculitis by imaging by Week 26
    • Time to elevated ESR by week 26
    • Time to elevated CPR by week 26
    • Time to signs/symptoms of GCA or new or worsening vasculitis by week 26
    • Cumulative steroid dose at Week 26 and at the end of the Washout Safety Follow-up Period
    • Change in clinical GCA assessments (including NRS and FACIT) over time
    • Change in quality-of-life (EO-5D and SF-36) over time
    E.5.2.1Timepoint(s) of evaluation of this end point
    Appro. 44 weeks after the start of the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    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 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) 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA36
    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
    Belgium
    Croatia
    Estonia
    Germany
    Ireland
    Italy
    Netherlands
    New Zealand
    Poland
    Serbia
    Slovenia
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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 years0
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months11
    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: 20
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 52
    F.4.2.2In the whole clinical trial 70
    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)
    After subjects complete the 26-week double blind treatment period, they will discontinue and wash off of blinded KPL-301 or placebo during a 12-week Washout Period, which includes close safety follow-up and monitoring for potential GCA flares. After the final Washout Safety Follow-up visit (Week 38) has been completed, the subjects will exit the trial and should be transitioned to SoC per investigator judgement.
    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 Decision2018-10-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-09-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-12-11
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