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    Summary
    EudraCT Number:2012-001645-41
    Sponsor's Protocol Code Number:JAK115919
    National Competent Authority:Estonia - SAM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-11-27
    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 ConcernedEstonia - SAM
    A.2EudraCT number2012-001645-41
    A.3Full title of the trial
    An adaptive Phase II study to evaluate the efficacy, pharmacodynamics, safety and tolerability of GSK2586184 in patients with active systemic lupus erythematosus.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the efficacy and safety of GSK2586184 in SLE
    A.4.1Sponsor's protocol code numberJAK115919
    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 SponsorGlaxoSmithKline Research and Development Limited
    B.1.3.4CountryUnited Kingdom
    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 supportGSK
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointClinical Trials Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road
    B.5.3.2Town/ cityUxbridge
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 02089904466
    B.5.5Fax number+44020 89901234
    B.5.6E-mailGSKClinicalSupportHD@gsk.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 nameGSK2586184
    D.3.2Product code GSK2586184
    D.3.4Pharmaceutical form Tablet
    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 INNGSK2586184
    D.3.9.1CAS number 1206163-45-2
    D.3.9.2Current sponsor codeGSK2586184
    D.3.9.3Other descriptive nameN-(5-{4-[(3,3-dimethyl-1-azetidinyl)carbonyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.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 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 nameGSK2586184
    D.3.2Product code GSK2586184
    D.3.4Pharmaceutical form Tablet
    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 INNGSK2586184
    D.3.9.1CAS number 1206163-45-2
    D.3.9.2Current sponsor codeGSK2586184
    D.3.9.3Other descriptive nameN-(5-{4-[(3,3-dimethyl-1-azetidinyl)carbonyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 placeboTablet
    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
    Systemic Lupus Erythematosus
    E.1.1.1Medical condition in easily understood language
    Systemic Lupus Erythematosus (chronic autoimmune disorder)
    E.1.1.2Therapeutic area Body processes [G] - Bones and nerves physological processes [G11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level PT
    E.1.2Classification code 10042945
    E.1.2Term Systemic lupus erythematosus
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To estimate the relationship between dose of GSK2586184 and pharmacodynamic effect on expression of selected messenger ribonucleic acid (mRNA) transcripts following 2 weeks of treatment in SLE patients
    • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by SELENA SLEDAI score following 12 weeks of treatment in SLE patients
    • To evaluate the safety and tolerability of repeat doses of GSK2586184 in SLE patients.
    E.2.2Secondary objectives of the trial
    • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by the SRI following 12 weeks of treatment in SLE patients
    • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by the SLEDAI-2K and S2K RI-50 scores following 12 weeks of treatment in SLE patients
    • To estimate the relationship between changes in the expression of selected mRNA transcripts following dosing with GSK2586184 and clinical response
    • To assess the pharmacokinetics of GSK2586184 in SLE patients.
    • To define the PK/PD relationship of JAK-1 inhibition on the interferon (IFN) transcriptional signature biomarker following 2 weeks of treatment.
    • To define the PK/PD relationship of JAK-1 inhibition on clinical response parameters following 12 weeks of treatment.
    • To estimate any impact of GSK2586184 treatment on patient reported outcomes
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligible for enrolment in the study must meet all of the following criteria:
    1. Age and Gender: Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent.
    2. SLE classification: Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria, with 4 or more of the 11 ACR criteria present, serially or simultaneously during any interval or observation.
    3. Severity of disease: Have clinically active SLE disease defined as a SELENA SLEDAI score ≥8 at screening during the 35-day screen period.
    4. Auto antibodies: Are serologically active having unequivocally positive antinuclear antibody (ANA) or anti-double stranded DNA (anti-dsDNA) antibody test results from 2 independent time points as follows:
    • Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study’s central laboratory results. A positive test is defined as a positive ANA test equivalent to a titre ≥1:80 as defined in the central laboratory manual and/or a positive anti-dsDNA (≥30 IU/mL) serum antibody.
    OR
    • One positive historical test result and 1 positive test result for either ANA or anti-dsDNA during the screening period.
    Historical documentation of a positive test of ANA (e.g., ANA by HEp-2 titre) or anti-dsDNA antibody (e.g., anti-dsDNA by Farr assay) must include the date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive vs. negative OR negative,
    equivocal/borderline positive). Only unequivocally positive values as defined in the laboratory’s reference range are acceptable; borderline values will not be accepted.
    5. Treatment for SLE: patient stable on either no treatment or on a stable dose of corticosteroids (≤15mg/day prednisone or prednisone equivalent or less) stable for a minimum of 30 days prior to screening and through to Day 0/Randomisation and /or an anti-malarial therapy[hydroxychloroquine (≤400mg daily dose) or chloroquine (≤ 500mg daily dose) or quinacrine ( ≤100mg daily dose)]for a minimum of 60 days prior to the Day 0/Randomisation Visit. Subjects receiving azathioprine (≤ 2mg/kg/day or ≤ 150mg/day, whichever is greater) or mycophenolate mofetil (≤ 1.5g/day), or MTX (≤20mg/week), either alone or in addition to steroids and / or an anti-malarial therapy as described above, if they have been on a stable dose of azathioprine OR
    mycophenolate mofetil OR MTX for a minimum of 90 days prior to the Day 0 /Randomisation Visit.
    For those subjects on alternating day dosing of steroids, use the average of 2 daily doses to calculate the average daily steroid dose.
    6. ECG: Single QTc, < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
    7. Prevention of Pregnancy:
    Females: A female subject is eligible to participate if she is not pregnant, as confirmed by a negative serum human chorionic gonadotrophin (hCG) test, or lactating and at least one of the following conditions applies: Please refer to page 41 bullet point 7 of the study protocol for details.
    8. Informed consent: Capable of giving written informed consent, including confirmation that the subject is not mentally or legally incapacitated, and compliance with the requirements and restrictions listed in the consent form.
    French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
    E.4Principal exclusion criteria
    Subjects meeting any of the following criteria must not be enrolled in the study:
    1. Kidney Disease
    2. CNS Disease
    3. Alcohol Abuse
    4. Substance Abuse
    5. Hepatitis B
    6. Hepatitis C
    7. HIV
    8. Previous investigational product exposure
    9. Previous and current medication
    10. Prior biological therapies
    11. Transplantation
    12. Uncontrolled Other Diseases
    13. Surgery and Other Conditions
    14. Cancer
    15. Infections
    16. Mycobacterium Tuberculosis
    17. Haematology
    18. Serum immunoglobulin (Ig) levels
    19. Liver Function Tests
    20. Other laboratory abnormalities
    21. Drug sensitivity
    22. Blood donation
    * Please refer to the study protocol section 5.3 Exclusion Criteria pages 43-44 for further details.
    E.5 End points
    E.5.1Primary end point(s)
    1. Interferon transcriptional signature biomarker expression over time (Interim Analysis 1, Primary Endpoint)
    2. SELENA SLEDAI score over time (Interim Analysis 2, 3 and final analysis, Primary Endpoint)
    3. Change from baseline for blood pressure, heart rate and temperature over time.
    4. Change from baseline in clinical chemistry and hematology parameters over time.
    5. Number and severity of adverse events during the study period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    * Primary endpoints 1 to 5 will be evaluated during the 12 week treatment period.
    * Primary endpoint 1 is the key decision making pharmacodynamic endpoint at Interim Analysis 1 after the first 25 subjects have been treated for 2 weeks
    * Primary endpoint 2 is the key decision making clinical efficacy primary endpoint at Interim Analyses 2 and 3 (if conducted)
    E.5.2Secondary end point(s)
    1. SRI Response Rate over time. Response is defined as:
    ≥ 4 point reduction from baseline in the SELENA SLEDAI score,
    AND
    No worsening (increase of <0.30 points from baseline) in Physicians Global Assessment (PGA)
    AND
    No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with baseline.
    To evaluate the response over time, the percentage of subjects achieving a response on the composite endpoint, and each of the components of this endpoint, will be presented by visit.
    2. Change from baseline in SLEDAI-2K score and the S2K RI-50 score during 12 weeks of treatment with GSK2586184
    3. Individual plasma concentrations of GSK2586184 and data permitting, summary PK parameters.
    4. Mean change from baseline in Short Form-36 Health Survey (SF-36) score (8 domains) at Week 12.
    5. Mean change from baseline in Brief Fatigue Inventory (BFI) score (9 items) at Weeks 2, 4, 6, 8, 10 and 12.
    6. Mean change from baseline in Brief Pain Inventory (BPI) (short form) score (15 items) at weeks 2, 4, 6, 8, 10 and 12.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary endpoints 1 through 6 will be evaluated during the 12 week treatment period.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability of GSK2586184 in adult patients with active SLE.
    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 No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Adaptive
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA44
    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
    Argentina
    Brazil
    Chile
    Hong Kong
    Korea, Republic of
    Peru
    South Africa
    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
    LSLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 175
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 75
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 137
    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)
    The investigator is responsible for ensuring that consideration has been given to the poststudy
    care of the patient’s medical condition whether or not GSK is providing specific post study treatment.
    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 Decision2012-12-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-12-20
    P. End of Trial
    P.End of Trial StatusCompleted
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