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    Summary
    EudraCT Number:2010-020993-41
    Sponsor's Protocol Code Number:LPZ114458
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-05-06
    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 ConcernedSweden - MPA
    A.2EudraCT number2010-020993-41
    A.3Full title of the trial
    A phase 2a study to evaluate the effect of rilapladib (SB-659032)
    on biomarkers related to the pathogenesis and progression of
    Alzheimer’s disease.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the effect of rilapladib (SB 659032) on Alzheimer’s disease.
    A.4.1Sponsor's protocol code numberLPZ114458
    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 Ltd
    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 supportGlaxoSmithKline
    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 pointGSK Clinical Support Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressGlaxoSmithKline, Iron Bridge Road, Stockley Park West
    B.5.3.2Town/ cityUxbridge
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number440208990 4466
    B.5.5Fax number440208990 4968
    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 namerilapladib
    D.3.2Product code SB-659032
    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.3.9.2Current sponsor codeSB-659032
    D.3.9.3Other descriptive namerilapladib
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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
    Alzheimer's Disease
    E.1.1.1Medical condition in easily understood language
    Alzheimer's Disease is a brain disease that causes problems with memory, thinking and behavior.
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10001896
    E.1.2Term Alzheimer's disease
    E.1.2System Organ Class 10029205 - Nervous system 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 examine in an exploratory manner whether rilapladib produces changes in CSF biomarkers that are consistent with effects on increased CNS Aβ clearance in AD patients and whether these findings are associated with changes in CSF neurodegenerative markers and selected cognitive endpoints.
    E.2.2Secondary objectives of the trial
    - To examine the effects of rilapladib on BBB permeability (CSF albumin
    quotient), peripheral Aβ levels (Aβ42 and Aβ40) and plasma Lp-PLA2 activity.
    - To further evaluate the effects of rilapladib on cognition.
    - To assess the safety and tolerability of rilapladib over a 24 week treatment period.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. A clinical diagnosis of possible Alzheimer’s disease in accordance with the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria, with radiological (Magnetic Resonance Imaging [MRI] or Computed Tomography [CT]) evidence of significant cerebrovascular disease (CVD), assessed within the last 12 months, including at least one of the following:
    a. CT: Extensive periventricular and deep white matter lesions: patchy or diffuse symmetrical areas of low attenuation (intermediate density between normal white matter and cerebrospinal fluid), with ill-defined margins extending to the centrum semiovale, and at least one lacunar infarct.
    And/Or
    b. MRI: White matter lesions: extending caps or irregular halo or diffusely confluent hyperintensities or extensive white matter changes
    And/Or
    c. Lacunar cases: Multiple lacunes (e.g. > 5) in the deep grey matter.
    2. Male or female between 50 and 80 years of age inclusive, at the time of signing the informed consent.
    3. Subject has a documented history of at least 6 months of ongoing Alzheimer's disease therapy (AChEIs and/or ± memantine) with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).
    4. Mini-Mental Status Examination (MMSE) score between 20 and 26 at Screening.
    5. Clinical Dementia Rating Scale (CDR) score of 0.5 or 1.0 at Screening.
    6. A female subject is eligible to participate if she is of:
    a. Non-childbearing potential defined as pre-menopausal females with a
    documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].
    NB: Females on hormone replacement therapy (HRT) and whose
    menopausal status is in doubt will be required to use one of the
    contraception methods described in the protocol.
    b. Child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until completion of the follow-up visit.
    7. Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if the subject is unable to provide informed consent due to cognitive status, the subject will provide assent and full written informed consent will be provided by a legally acceptable representative
    8. The subject has a dedicated caregiver who is willing to supervise participation in the study (i.e. clinic visits, medication). A non-cohabiting caregiver must spend sufficient time with the subject so that, in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behaviour for the purpose of the baseline CDR assessment, and to oversee the subject’s compliance and to report on their health throughout the study. This would normally be possible
    when the caregiver spends a few hours each day with the subject.
    9. In the opinion of the investigator, the subject has the ability to comply with study procedures (cognitive and other testing) and is fluent in the language used for the administration of the cognitive tests.
    E.4Principal exclusion criteria
    1. History and/or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. structural or developmental abnormality, epilepsy, infectious, degenerative or inflammatory/demyelinating CNS conditions such as Parkinson’s disease and frontotemporal dementia (in accordance with the Work Group on Frontotemporal Dementia and Pick’s Disease criteria)
    2. History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that would interfere with participation in the study; major depressive disorder in the past year; current active depression requiring initiation of treatment
    3. Evidence of: current vitamin B12 deficiency, positive syphilis serology or active thyroid dysfunction.
    4. History of alcohol or other substance abuse.
    5. History of intra cerebral haemorrhage due to: CAA, uncontrolled hypertension, cerebral arteriovenous malformation, coagulopathy, CNS vasculitis or any other condition that the investigator and/or medical monitor considers as a relevant risk factor for intracerebral haemorrhage
    6. Recent CV event defined as:
    a. ST-elevation MI or non-ST-elevation MI,
    b. coronary revascularization (PCI or CABG)
    c. stroke
    d. resuscitated sudden death
    e. prior carotid surgery or stenting procedure
    7. Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy (either systolic blood pressure >160mmHg or diastolic blood pressure >110mmHg).
    8. QTcB interval >450 msec; or QTcB > 480 msec in subjects with bundle branch block based on ECG assessment at the Screening.
    9. HbA1c >12.0 at Screening, or uncontrolled diabetes.
    10. History of glaucoma or any other findings in the baseline eye exam.
    11. History of adult asthma (or reactive airway disease).
    12. Previous history of anaphylaxis, severe allergic reaction or history of
    hypersensitivity to any of the components of the formulation.
    13. Significant abnormalities on clinical chemistry, haematology or urinalysis.
    14. History of chronic viral hepatitis or other chronic hepatic disorders.
    15. Abnormal Screening blood tests regarding: ALT or AST, alkaline phosphatase and bilirubin, creatinine clearance
    16. Other clinically significant abnormality on physical (including neurological), laboratory or ECG examination that could be detrimental to the subject.
    17. Planned major surgery within the study period.
    18. Use of systemic steroids or other immunosuppressants within the last 30 days.
    19. Current treatment with barbiturates, MAO inhibitors, butyrophenones, phenothiazines and other “conventional” antipsychotic within 30 days or 5 half-lives prior to Screening, whichever is longer.
    20. Treatment with antidepressants, (other than MAO inhibitors), thyroid hormones, atypical antipsychotics (e.g. risperidone), benzodiazepines and other sedatives / hypnotics unless prescribed at a stable dose for at least 2 months prior to Screening.
    21. Current treatment with known potent inhibitors of CYP3A4.
    22. Current treatment with known potent Pgp inhibitors.
    23. Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision in the 6 months prior to screening and/or during study
    24. Investigational medications or devices including symptomatic AD treatment during the 60 days prior to the Screening visit, or within 5 half-lives of use of the investigational drug prior to the Screening Visit, whichever is longer.
    25. Participation in another investigational drug (with the exception of anti-amyloid monoclonal antibodies [mAbs]) or device study where subject was treated chronically (i.e. > 1 single dose) with a study agent intended to impact AD progression during the 12 months prior to Screening.
    26. Subjects who pose a significant suicide risk.
    27. Subject or caregiver is an immediate family member or employee of the participating Investigator, any of the participating site staff or GSK staff.
    28. Any contraindication to lumbar puncture or insertion of CSF catheter including but not limited too:
    a. Thrombocytopenia or other coagulation disorders (including subjects receiving coumarin-derived anti-coagulants or low-molecular-weight heparin). Screening INR, prothrombin time and platelet results should be reviewed as part of this assessment of contraindication to LP.
    b. The presence of cutaneous or soft tissue infection overlying or
    adjacent to the site of lumbar puncture.
    c. Previous spinal surgery that could complicate access to the
    subarachnoid space.
    d. Suspicion of increased intracranial pressure due to a cerebral mass.
    29. Subjects with both parents of Japanese, Chinese, or Korean ancestry and plasma Lp-PLA2 activity ≤ 20.0nmol/mL.1
    NB. This will require a sample to be taken at Screening for subjects with this ancestry for assessment of plasma Lp-PLA2 activity.
    E.5 End points
    E.5.1Primary end point(s)
    • Change from baseline in CSF Aβ42, Aβ40 and Aβ42/ Aβ40 ratios at Week 24.
    • Change from baseline in CSF tau and P-tau measures at Week 24.
    • Change from baseline in the CogState battery working memory/executive function composite score at Week 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    E.5.2Secondary end point(s)
    • Change from baseline in CSF albumin quotients at Week 24.
    • Change from baseline in plasma levels of Aβ42, Aβ40 and ratio Aβ42/Aβ40 at Week 24.
    • Change from baseline in plasma Lp-PLA2 activity at Week 24.
    • Change from baseline in CogState battery overall composite score.
    • Change from baseline in CogState battery attention composite score.

    Safety Endpoints
    • Assessment of safety and tolerability by analysis of AE data and changes from
    baseline in vital signs, clinical laboratory values, neurological examination, EM
    of peripheral blood mononuclear cells and electrocardiograms (ECGs).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 24
    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 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) 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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    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
    Bulgaria
    Canada
    Germany
    Italy
    Spain
    Sweden
    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
    LPLV
    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 months6
    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 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.1.1Number of subjects for this age range: 0
    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: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 102
    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 120
    F.4.2.2In the whole clinical trial 120
    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)
    Not applicable.
    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 Decision2011-07-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-08-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-02-18
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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