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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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:2018-000998-72
    Sponsor's Protocol Code Number:4083-006
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-07-18
    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 ConcernedGermany - PEI
    A.2EudraCT number2018-000998-72
    A.3Full title of the trial
    A Phase 2, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects with Moderate to Severe Atopic Dermatitis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study to test the safety and possible benefits of an investigational study drug, KHK4083, in patients with atopic dermatitis.
    A.4.1Sponsor's protocol code number4083-006
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03703102
    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 SponsorKyowa Kirin Co., Ltd.
    B.1.3.4CountryJapan
    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 supportKyowa Kirin Co., Ltd
    B.4.2CountryJapan
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKyowa Kirin Co., Ltd
    B.5.2Functional name of contact pointRegulatory Affairs Department
    B.5.3 Address:
    B.5.3.1Street Address1-9-2 Otemachi
    B.5.3.2Town/ cityChiyoda-ku, Tokyo
    B.5.3.3Post code100-0004
    B.5.3.4CountryJapan
    B.5.4Telephone number+8135205-7219
    B.5.5Fax number+8135205-7165
    B.5.6E-mailHQYJ@kmail.kyowa-kirin.co.jp
    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 nameKHK4083
    D.3.2Product code KHK4083
    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 INNNot available
    D.3.9.2Current sponsor codeKHK4083
    D.3.9.4EV Substance CodeSUB178562
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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
    Moderate to Severe Atopic Dermatitis
    E.1.1.1Medical condition in easily understood language
    Moderate to severe eczema
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10003639
    E.1.2Term Atopic dermatitis
    E.1.2System Organ Class 100000004858
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of four dose regimens of KHK4083 compared to placebo as measured by the change from baseline in Eczema Area and Severity Index (EASI) score following multiple subcutaneous (SC) injections for 16 weeks in subjects with moderate to severe AD.
    E.2.2Secondary objectives of the trial
    To evaluate the effects on:
    • skin symptoms
    • itching and sleeping
    • quality of life (QoL)
    following multiple SC injections of KHK4083 for 16 weeks in comparison with placebo in subjects with moderate to severe AD.

    To evaluate the effects on
    • skin symptoms
    • itching and sleeping
    • QoL
    following multiple SC injections of KHK4083 for 36 weeks in subjects with moderate to severe AD.

    To evaluate the safety of multiple SC injections of KHK4083 in subjects with moderate to severe AD
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Voluntarily signed informed consent to participate in the study;
    2) Men and women ≥18 years at the time of informed consent;
    3) Chronic AD, according to American Academy of Dermatology Consensus Criteria (Eichenfield et al, 2014) or the local diagnostic criteria, that has been present for at least 1 year before screening;
    4) EASI score ≥16 at screening and baseline;
    5) IGA score ≥3 (moderate) at both screening and baseline;
    6) BSA ≥10% at both screening and baseline;
    7) Documented recent history (within 1 year prior to screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks);
    8) Women of childbearing potential (WOCBP) and fertile men must agree to use highly effective contraceptive methods per the approved local guidance in each country from the time of informed consent to 6 months after the last dose of IP (for women) or from the start of IP administration to 6 months after the last dose of IP (for men). WOCBP must have a negative serum pregnancy test result at screening and a negative urinary pregnancy test result at baseline assessments.
    For Germany, WOCBP and fertile men must agree to use highly effective contraceptive methods that can achieve a failure rate of less than 1% per year from the time of informed consent to 6 months after the last dose of IP (for men). WOCBP must have a negative serum pregnancy test result at screening and a negative urinary pregnancy test result at baseline assessments and at each dose interval.
    Birth control methods considered highly effective used consistently and correctly include:
    • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
    - oral
    - intravaginal
    - transdermal
    • Progestogen-only hormonal contraception associated with inhibition of ovulation
    - oral
    - injectable
    - implantable
    • Intrauterine device
    • Intrauterine hormone-releasing system
    • Bilateral tubal occlusion
    • Vasectomised partner
    • Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of the study treatments).
    E.4Principal exclusion criteria
    1) Current or past history of clinically significant illness(es) deemed by the Investigator to be likely to affect the study conduct and assessments.
    2) Any of the following laboratory abnormalities at screening:
    • Serum creatinine: >1.5 mg/dL
    • AST or ALT: ≥2.5 times the upper limit of normal (ULN)
    • Neutrophil count: <1.5 x 10e3/μL
    • Other laboratory abnormalities that may affect the completion or evaluation of the study, as judged by the Investigator;
    3) Active malignancies, or onset or a history of treatment of malignancies within 5y prior to informed consent (except curatively treated in situ cervical carcinoma, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma);
    4) Past history of alcohol or substance abuse within 1y before screening visit; active alcohol dependence or drug dependence;
    5) Current or past history of any suicidal behavior;
    6) History of major immunologic reaction to any other biologic product or any excipient of KHK4083;
    7) History of ≥3 systemic infections requiring systemic administration (excluding oral administration) of antimicrobials, antifungals, or antivirals within 1y prior to baseline visit;
    8) Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4w before the baseline visit, or superficial skin infections within 2w before the baseline visit;
    9) Treatment with live vaccination within 12w prior to baseline visit. Inactivated vaccination is allowed;
    10) Treatment with any biological product (including an investigational product(IP)) within 12w or 5 half-lives, whichever is longer, prior to baseline visit;
    11) Treatment with 3 or more biological products (including an IP) within 2y before the baseline visit;
    12) Participation in a clinical or equivalent study and use of an IP (other than biologics) or unapproved medical device within 4w or 5 half-lives, whichever is longer, prior to baseline visit;
    13) Treatment with any of the following medications or therapies within 4w or 5 half-lives, prior to baseline visit;
    • Systemic corticosteroids (inhaled corticosteroids, eye, ear, or nasal drops containing corticosteroids are allowed, suppositories or enemas containing corticosteroids are not allowed)
    • Systemic treatment with methotrexate, mycophenolate, calcineurin inhibitors, thalidomide, or other immunosuppressants
    • Phototherapy for the treatment of AD
    • Janus kinase inhibitors
    14) Treatment with any of the following medications for the treatment of AD within 1w prior to baseline visit;
    • Topical corticosteroids
    • Topical calcineurin inhibitors or other immunosuppressive agents
    • Topical agents including crotamiton, Eucrisa®/crisaborole
    • Combination topical agents containing a corticosteroid or a calcineurin-inhibiting component or other immunosuppressive agents
    • Chinese herbal medicines
    15) Any planned surgical treatment or invasive procedure during the study;
    16) Any conditions not allowing for discontinuation of prohibited concomitant drugs or therapies;
    17) Pregnant or breastfeeding women, or women willing to become pregnant;
    18) Evidence of HIV infection or positive for HIV antibodies at screening; or current acquired, common variable or inherited, primary or secondary immunodeficiency;
    19) Positive test for active hepatitis B (HB) infection at screening defined as:
    • Positive for HBsAg;
    • Positive for anti-HBcAb or positive for HBV-DNA;
    If any HB tests has an indeterminate or the result cannot be interpreted with certainty, confirmatory testing as per local guidelines will be performed.
    20) Positive for anti-HC virus antibody at screening, and confirmed infection with HC virus by RNA or other test. If the HC test has an indeterminate result, confirmatory testing will be performed by an alternative method that is locally accepted;
    21) Evidence or history of active TB, either treated or untreated, or latent TB (defined as a positive purified protein derivative or interferon-gamma release assay test without evidence of clinically manifested active TB), the treatment of which was completed more than 12m before baseline visit or untreated. Evaluation of TB will be conducted according to the local standards of care or as determined by local guidelines and will include PPD or IGRA tests and may consist of history, physical examinations and chest X-ray.
    Subjects with latent TB who meet either of the following conditions can be enrolled:
    • Subjects with latent TB who have completed an appropriate course of anti-TB treatment as per local guidelines or standards of care within 12m before baseline visit.
    • Subjects with latent TB who have been receiving appropriate TB treatment as per local guidelines or standards of care for at least 28d before baseline visit.
    22) Previous participation in a study of KHK4083 and use of an IP;
    23) Other conditions unsuitable for participation in the study in the opinion of the Investigator.
    E.5 End points
    E.5.1Primary end point(s)
    • Percent change from baseline to Week 16 in EASI score
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and week 16
    E.5.2Secondary end point(s)
    Effects on skin symptoms following 16 weeks treatment
    • Achievement of 50%, 75%, or 90% reduction from baseline in EASI score (EASI-50, EASI-75, or EASI-90) at Week 16
    • Change from baseline to Week 16 in EASI score
    • Change and percent change from baseline to Week 16 in SCORAD score
    • Achievement of an Investigator’s Global Assessment (IGA) score of 0 or 1 and a reduction from baseline of ≥2 points at Week 16
    • Change from baseline to Week 16 in percent body surface area of involvement of AD (BSA)

    Effects on itching and sleeping following 16 weeks treatment
    • Change and percent change from baseline to Week 16 in pruritus NRS score
    • Change and percent change from baseline to Week 16 in sleep disturbance NRS score

    Effects on QoL following 16 weeks treatment
    • Change from baseline to Week 16 in Dermatology Life Quality Index (DLQI)

    Effects on skin symptoms following 36 weeks treatment
    • Change and percent change from baseline in EASI score at each time point
    • Achievement of EASI-50, EASI-75, or EASI-90 at each time point
    • Change and percent change from baseline in SCORAD score at each time point
    • Achievement of an IGA score of 0 or 1 and a reduction from baseline of ≥2 points at each time point
    • Change from baseline in percent BSA at each time point


    Effects on itching and sleeping following 36 weeks treatment
    • Change and percent change from baseline in pruritus NRS score at each time point
    • Change and percent change from baseline in sleep disturbance NRS score at each time point

    Effects on QoL following 36 weeks treatment
    • Change from baseline in DLQI at each time point

    Safety
    • Treatment-emergent adverse events (TEAEs)
    • Laboratory values
    • Vital signs
    • Standard 12-lead electrocardiogram (ECG)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Skin symptoms: baseline, week 1, week 2, biweekly to week 36 then every 4 weeks to week 56.
    Itching and sleeping: baseline, week 1, week 2, biweekly to week 36 then every 4 weeks to week 56.
    Safety: throughout study
    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 Yes
    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) 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 trial5
    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 concerned10
    E.8.5The trial involves multiple Member States No
    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
    Canada
    Germany
    Japan
    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 years2
    E.8.9.1In the Member State concerned months4
    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 months6
    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: 238
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 12
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 250
    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
    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 Decision2018-12-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-01-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-11-12
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