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    Summary
    EudraCT Number:2015-004711-21
    Sponsor's Protocol Code Number:20130287
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-05-10
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2015-004711-21
    A.3Full title of the trial
    Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab (AMG 145) on LDL-C in Subjects With Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed Dyslipidemia
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study is to evaluate evolocumab in people with type 2 diabetes mellitus with high cholesterol (hypercholesterolemia or mixed dyslipidemia).
    A.4.1Sponsor's protocol code number20130287
    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 SponsorAmgen Inc.
    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 supportAmgen Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ Medical Info - Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post code(CH-)6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@amgen.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 Yes
    D.2.1.1.1Trade name Repatha 140 mg solution for injection in pre-filled pen
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameEvolocumab
    D.3.2Product code AMG 145
    D.3.4Pharmaceutical form Solution for injection in pre-filled pen
    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 INNEVOLOCUMAB
    D.3.9.2Current sponsor codeAMG 145
    D.3.9.4EV Substance CodeSUB128552
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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 Yes
    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 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 nameEvolocumab
    D.3.2Product code AMG 145
    D.3.4Pharmaceutical form Solution for injection in cartridge
    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 INNEVOLOCUMAB
    D.3.9.2Current sponsor codeAMG 145
    D.3.9.4EV Substance CodeSUB128552
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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 Yes
    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
    D.8 Placebo: 2
    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
    Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed Dyslipidemia
    E.1.1.1Medical condition in easily understood language
    Type 2 diabetes mellitus with high cholesterol ( elevated LDL-cholesterol in blood) and/or mixed dyslipidemia (abnormal amounts of lipids in blood).
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10020604
    E.1.2Term Hypercholesterolemia
    E.1.2System Organ Class 10027433 - Metabolism and nutrition disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level PT
    E.1.2Classification code 10067585
    E.1.2Term Type 2 diabetes mellitus
    E.1.2System Organ Class 10027433 - Metabolism and nutrition disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10058110
    E.1.2Term Dyslipidemia
    E.1.2System Organ Class 10027433 - Metabolism and nutrition 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 evaluate the effect, tthe safety and tolerability of 12 weeks of subcutaneous (SC) evolocumab monthly (QM) compared with placebo QM on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in subjects with type 2 diabetes mellitus and hypercholesterolemia or mixed dyslipidemia on maximally tolerated dose of statin of at least moderate-intensity oral daily.
    E.2.2Secondary objectives of the trial
    To assess the effects of 12 weeks of SC evolocumab QM compared
    with placebo QM, in subjects with type 2 diabetes mellitus and hypercholesterolemia or mixed dyslipidemia in combination with maximally tolerated dose of statin of at least moderate-intensity oral daily on the following:
    - Change from baseline in LDL-C, and percent change from baseline in non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), total cholesterol (TC), lipoprotein(a) (Lp[a]), triglycerides, HDL-C, and very low-density lipoprotein cholesterol (VLDL-C)
    - Percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L)
    - Percent of subjects attaining a 50% reduction in LDL-C from baseline
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Subject has provided written informed consent

    -Male or female ≥ 18 years of age at signing of informed consent

    -Type 2 diabetes mellitus:
    •with hemoglobin A1c (HbA1c) < 10%
    •receiving pharmacologic treatment for diabetes mellitus for ≥ 6 months prior to screening
    •stable diabetes therapy prior to randomization to IP and not expected to change during the duration of study participation. Stable diabetes therapy is defined as no new agents added, and no dose change of any antihyperglycemic drug within 2 months prior to randomization and daily insulin dose not changed by > 25% and > 25 units within 1 month prior to randomization

    -Subject must be on maximally tolerated dose of statin of at least moderate intensity at signing of the informed consent (see Appendix D) and is expected to remain on stable statin intensity for the duration of study in the opinion of the investigator:
    •subjects without known clinical CVD must be on at least moderate-intensity statin prior to randomization
    • subjects with known clinical CVD must be on high intensity statin (or moderate intensity if certified by principal investigator to be highest tolerated dose) prior to randomization). Clinical CVD is defined as a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.

    -Subjects without known clinical CVD must have a fasting LDL-C during lipid stabilization of ≥ 100 mg/dL (2.6 mmol/L) or non-HDL-C ≥ 130 mg/dL (3.4 mmol/L) as determined by the central laboratory

    -Subjects with known clinical CVD must have a fasting LDL-C during lipid stabilization of ≥ 70 mg/dL (1.8 mmol/L) or Non-HDL-C ≥ 100 mg/dL (2.6 mmol/L) as determined by the central laboratory

    -Fasting triglycerides ≤ 600 mg/dL (6.8 mmol/L) by central laboratory prior to randomization

    -Subject tolerates screening placebo injection

    E.4Principal exclusion criteria
    -Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months prior to randomization

    -Uncontrolled hypertension defined as sitting systolic blood pressure (BP) > 180 mmHg or diastolic BP > 110 mmHg

    -Subject has taken a cholesterylester transfer protein inhibitor in the last 12 months prior to randomization, such as: anacetrapib, dalcetrapib, or evacetrapib

    -Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate < 20 mL/min/1.73 m2 during screening

    -Persistent active liver disease or hepatic dysfunction, defined as Child-Pugh score of C

    -Female subject of childbearing potential not willing to use an acceptable method(s) of effective birth control during the screening/lipid stabilization period, during treatment with IP and for an additional 15 weeks after the end of treatment with IP.

    Female subjects of non-childbearing potential are not required to use contraception during the study and include those who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or who are postmenopausal. Postmenopausal is defined as 12 months of spontaneous and continuous amenorrhea in a female ≥ 55 years old; or age < 55 years but no spontaneous menses for at least 2 years; or age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved.

    Acceptable methods of effective birth control include:
    •true sexual abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception),
    •vasectomized partner (provided that partner is the sole sexual partner of the female participant who is of childbearing potential and that the vasectomized partner has received medical assessment of the surgical success),
    •bilateral tubal ligation/occlusion, use of hormonal birth control methods (oral, intravaginal, [eg, vaginal ring], transdermal, injectable, or implantable),
    • intrauterine devices,
    •intrauterine hormonal releasing system, or
    •2 barrier methods (each partner must use one barrier method) and the female partner must use if available spermicide in addition to a barrier – males must use a condom; females must choose either a diaphragm, OR cervical cap, OR contraceptive sponge. (Note: If spermicide is not commercially available in the country or region, the two barrier method without spermicide iswould then be considered acceptable.).
    Note: Additional medications given during the study may alter the contraceptive requirements. These additional medications may require an increase in the number of contraceptive methods, the change in type of contraceptive methods and/or length of time that contraception is to be utilized and/or length of time breastfeeding is to be avoided. The investigator is to discuss these contraceptive changes with the study subject.

    - Female subject is pregnant or breast feeding, or planning to become pregnant or planning to breastfeed during the screening/lipid stabilization period, during treatment with IP and for an additional 15 weeks after the end of treatment with IP

    -Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 1 year prior to randomization

    -Subject has previously received evolocumab or any other therapy to inhibit PCSK9

    -Currently receiving treatment in another investigational device or IP, or < 30 days since ending treatment on another investigational device or drug study(s) or planning to receive other investigational procedures while participating in this study

    -Subject has known sensitivity to any of the active substances or their excipients to be administered during dosing, eg, carboxymethylcellulose

    -Subject likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge

    - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

    E.5 End points
    E.5.1Primary end point(s)
    - Mean percent change from baseline in LDL-C at weeks 10 and 12
    - Percent change from baseline in LDL-C at week 12
    - Subject incidence of treatment emergent adverse events
    - Safety laboratory values and vital signs at each scheduled assessment
    E.5.1.1Timepoint(s) of evaluation of this end point
    At day 1, week 8, week 10, and week 12.
    E.5.2Secondary end point(s)
    For the mean of weeks 10 and 12 and for week 12:
    • Tier 1
    − Change from baseline in LDL-C
    − Percent change from baseline in non-HDL-C
    − Percent change from baseline in ApoB
    − Percent change from baseline in TC
    − Achievement of target LDL-C < 70 mg/dL (1.8 mmol/L)
    − LDL-C response (50% reduction of LDL-C from baseline)

    • Tier 2
    − Percent change from baseline in Lp(a)
    − Percent change from baseline in triglycerides
    − Percent change from baseline in HDL-C
    − Percent change from baseline in VLDL-C
    E.5.2.1Timepoint(s) of evaluation of this end point
    At day 1, week 8, week 10, and week 12.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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) 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 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.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    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
    Mexico
    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 years
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days15
    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: 400
    F.1.3Elderly (>=65 years) Yes
    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 state70
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 400
    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 Decision2016-05-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-09-05
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