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    Summary
    EudraCT Number:2014-005142-21
    Sponsor's Protocol Code Number:MLN1202-2005
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2015-06-16
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2014-005142-21
    A.3Full title of the trial
    A Multicenter, Randomized, Double Blind, Placebo Controlled, Proof of Concept, Phase 2 Study to Evaluate the Efficacy and Safety of Weekly Subcutaneous MLN1202, in Improving Diabetic Nephropathy Subjects with Macroalbuminuria
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    MLN1202 75, 105, 150 mg as add-on to ACE/ARB to treat Diabetic Nephropathy
    A.3.2Name or abbreviated title of the trial where available
    MLN1202 75, 105, 150 mg as add-on to ACE/ARB to treat Diabetic Nephropathy
    A.4.1Sponsor's protocol code numberMLN1202-2005
    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 SponsorTakeda Development Centre Europe 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 supportTakeda Development Centre Americas, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTakeda Development Centre Americas, Inc.
    B.5.2Functional name of contact pointMedical Director, Clinical Science
    B.5.3 Address:
    B.5.3.1Street AddressOne Takeda Parkway
    B.5.3.2Town/ cityDeerfield
    B.5.3.3Post codeIL60015
    B.5.3.4CountryUnited States
    B.5.4Telephone number001224554 6500
    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 nameMLN1202
    D.3.2Product code MLN1202
    D.3.4Pharmaceutical form Lyophilisate for 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 INNplozalizumab
    D.3.9.1CAS number 1610761-46-0
    D.3.9.2Current sponsor codeMLN1202
    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.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
    Diabetic Nephropathy:
    Adults (age 18 - 90 years inclusive) with type 2 diabetes, an eGFR of 25-59 mL/min/1.73 m2, and with macroalbuminuria (>300 mg/g) will be randomized.
    E.1.1.1Medical condition in easily understood language
    Diabetic kidney disease (patients with type 2 diabetes)
    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 18.0
    E.1.2Level PT
    E.1.2Classification code 10061835
    E.1.2Term Diabetic nephropathy
    E.1.2System Organ Class 10038359 - Renal and urinary 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 characterize the effects of 85 days treatment with MLN1202 on urinary albumin-creatinine ratio (UACR) in subjects with type 2 diabetes, advanced kidney disease (diabetic nephropathy) and macro-albuminuria (UACR>300 mg/g) based on an average of 3 consecutive days first morning void sample collection.
    E.2.2Secondary objectives of the trial
    Secondary Objectives:
    To characterize the effect of MLN1202 on urinary albumin-creatinine ratio over time.

    To characterize the effect of MLN1202 on total protein-creatinine ratio over time.

    Additional Objectives:
    To characterize the effect of study drug on glycosylated hemoglobin fraction (HbA1c); high sensitivity C-reactive protein (hs-CRP); homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function HOMA-BCF; and renal function, as measured by creatinine.
    To assess the safety and tolerability of study drug; evaluate the PK of MLN1202 given by SC injection in patients with CKD.
    To evaluate the correlation between genetic markers and the effect of MLN1202 on UACR; subject’s pain during weekly SC injections; the role of baseline urinary MCP-1 as a biomarker for the effect of MLN1202 on albuminuria.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subject eligibility is determined according to the following criteria:

    1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.

    2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

    3. At the time of Screening the subject is male or female and aged 18-90 years inclusive at first dose of study medication.

    4. The subject was previously diagnosed with type 2 diabetes mellitus per ADA criteria.

    5. The subject has an estimated glomerular filtration rate based on serum creatinine (eGFR, determined by MDRD equation) of 25-59 mL/min/1.73 m(2) at Screening.

    6. The subject has been on a stable dose of ACE inhibitor or ARB for 8 weeks prior to Screening.

    7. The subject has residual albuminuria despite stable treatment with an ACE inhibitor or an ARB for at least 8 weeks prior to Screening (urine albumin:creatinine ratio [UACR] of > 300 mg/g creatinine, inclusive at Screening).

    8. The subject has HbA1c test result less than or equal to 10.5% at screening.

    9. Subject regularly using DPP4i or SGLT2 to treat diabetes has been on a stable dose and regimen within 2 months prior to Screening.

    10. All patients who are not surgically sterile or post-menopausal, or whose partners are not surgically-sterile or postmenopausal, must use two effective birth control methods or abstain from intercourse during this study.
    E.4Principal exclusion criteria
    Any subject who meets any of the following criteria will not qualify for entry into the study:

    1. Subject has received any investigational compound within 90 days prior to Screening.

    2. The subject is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

    3. Subject is taking any combination of dual RAS inhibition (such as an ACE inhibitor and an ARB or an ACE inhibitor and a mineralocorticoid receptor antagonist).

    4. Subject has type 1 diabetes mellitus or a history of ketoacidosis.

    5. Subject has poorly-controlled blood pressure (systolic blood pressure >160 or diastolic blood pressure >110, with blood pressure measured in the seated position after at least 5 minutes of rest) at Screening and Day 1.

    6. Subject has received dialysis within 3 months of Screening.

    7. Subject has infectious diseases or leg ulcers at Screening (all per discretion of Principal Investigator [PI]).

    8. Subject has severe concurrent disease which, in the judgment of the investigator, would interfere significantly with the assessments of safety and efficacy during this study.

    9. Subject with known infection with human immunodeficiency virus (HIV), or a positive test for Hepatitis B, Hepatitis C, or TB at Screening.

    10. Subject has used long-term immune suppressants, steroid therapy (except for topical use or inhalation), chronic use of non-steroidal anti-inflammatory drug (NSAIDs), cyclooxygenase type 2 (COX-2) inhibitors within 2 weeks prior to Screening. Short-term use is defined as a duration of ≤4 weeks of continuous use.

    11. In the judgment of the principal investigator, patients who are likely to be non-compliant or uncooperative during the study.

    12. Subjects with known non-diabetic kidney disease (such as autosomal dominant polycystic kidney disease (ADPCKD), IgA nephropathy, focal segmental glomerulosclerosis, or obstructive uropathy). Hypertensive nephrosclerosis superimposed on diabetic kidney disease is acceptable.

    13. Subject had a previous renal transplant.

    14. Subject has hypersensitivity to other monoclononal antibodies (mAb) or to any component of the formulation of MLN1202.

    15. The subject has history of malignancy within the previous 5 years (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin).

    16. Subject is symptomatic with dysuria, and has a positive urine culture at screening.




    E.5 End points
    E.5.1Primary end point(s)
    Efficacy: The primary endpoint for this study is UACR at 85 days, relative to the baseline (average of 3 consecutive first in the morning urine voids).

    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 85, relative to baseline average of 3 consecutive first in the morning voids
    E.5.2Secondary end point(s)
    Secondary endpoints for this study are:

    • UACR change from baseline over time at Day 29, 57, 85, and 113, (these collections will be single first morning void with the exception of Day 85 and 113 which will use the average of 3 consecutive first morning voids).

    • Urinary protein:creatinine change from baseline over time at Day 29, 57, 85, and 113, relative to baseline.

    Additional Endpoints:
    • UACR change from baseline over time at Day 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 113 (these collections will be single first morning voids with the exception of Days 85 and 113 which will use the average of 3 consecutive first morning voids).
    • Change from Baseline in plasma glycosylated hemoglobin at Day 29, 57, 85, and 113.
    • Percent change from Baseline in serum hs-CRP at Day 29, 57, 85, and 113.
    • Change from Baseline in HOMA-IR and HOMA-BCF at Day 85.
    • Change from Baseline in serum creatinine at Day 29, 57, 85, and 113.
    • Change from Baseline in eGFR at Day 29, 57, 85, and 113.
    • The safety and tolerability of therapy will be assessed by collected AEs, labs, vital signs, physical examination, and electrocardiogram (ECG).
    • Pharmacokinetic parameters of MLN1202 in subjects with chronic kidney disease.
    • A 1-10 pain scale measures [Pain Assessment Scale, Appendix G] will be used to evaluate subject’s pain during weekly SC injections.

    Pharmacodynamic Endpoints:
    The following pharmacodynamic (PD) parameters will be determined:
    • Concentrations of MCP-1 in serum and urine.
    • Counts and relative percentages of monocyte and neutrophil populations (from differential white blood cell counts and flow cytometry of classical, inflammatory and intermediate monocytes, and mature, intermediate, and immature neutrophils in peripheral blood).
    • Change from Baseline in renal tumor necrosis factor alpha [TNF-α].

    Immunogenicity Endpoints:
    • Proportion of patients with positive ADA (monthly) during the study.
    • Proportion of patients with positive neutralizing ADA during the study.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary Endpoints:
    UACR at Day 29, 57, 85, and 113, change from baseline over time
    (Day 85 and 113 will use the average of 3 consecutive first morning voids)

    UPC change from baseline over time at Day 29, 57, 85, and 113.
    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 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 trial4
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Austria
    Denmark
    Mexico
    Peru
    Serbia
    Slovakia
    South Africa
    United States
    E.8.7Trial has a data monitoring committee Yes
    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 years1
    E.8.9.1In the Member State concerned months5
    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 months8
    E.8.9.2In all countries concerned by the trial days20
    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: 62
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 94
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-06-16. Yes
    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 state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 34
    F.4.2.2In the whole clinical trial 156
    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 study medication will not be available upon completion of the subject’s participation in the study. The subject should be returned to the care of a physician and standard therapies as required.
    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 Decision2015-08-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-06-17
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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