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    Summary
    EudraCT Number:2014-002072-92
    Sponsor's Protocol Code Number:B5161002
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2015-01-12
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-002072-92
    A.3Full title of the trial
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate The Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 In Ambulatory Boys With Duchenne Muscular Dystrophy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 Study to Evaluate The Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 In Duchenne Muscular Dystrophy
    A.4.1Sponsor's protocol code numberB5161002
    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 SponsorPfizer Inc. 235 East 42nd Street, New York, NY 10017
    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 supportPfizer Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc
    B.5.2Functional name of contact pointClinical Trials.gov Call Centre
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York, NY
    B.5.3.3Post code10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1800 718 1021
    B.5.5Fax number+1303 739 1119
    B.5.6E-mailClinicalTrials.gov_Inquiries@pfizer.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1105
    D.3 Description of the IMP
    D.3.2Product code PF-06252616
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN-
    D.3.9.3Other descriptive namePF-06252616
    D.3.9.4EV Substance CodeSUB88240
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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) Yes
    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/infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Duchenne's Muscular Dystrophy
    E.1.1.1Medical condition in easily understood language
    Duchenne's Muscular Dystrophy
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10013801
    E.1.2Term Duchenne muscular dystrophy
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To determine the safety and tolerability of multiple ascending repeat IV doses of PF-06252616 in ambulatory boys with DMD.
    - To demonstrate the efficacy of treatment with IV doses of PF-06252616 based on an observed mean change from baseline on function (4 Stair Climb) as compared to placebo following 49 weeks of treatment.
    E.2.2Secondary objectives of the trial
    - To characterize the effects of PF-06252616 on muscle strength and other functional assessments compared to placebo
    - To evaluate the PD activity of PF-06252616 based on the percent change of muscle volume from baseline as compared to placebo
    - To evaluate the PD profile of PF-06252616 based on GDF-8 (myostatin) modulation in serum
    - To characterize the PK profile of PF-06252616
    - To evaluate the immunogenicity of PF-06252616
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Ambulatory boys age 6 to <10 years old (at the time of randomization), diagnosed with DMD. Diagnosis must be confirmed in subject’s medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor). Results must confirm the presence of a mutation in the dystrophin gene(s) which is clinically consistent with the diagnosis of DMD.
    2. Subjects who are able to perform the 4 stair climb in ≥0.33 but <1.6 stairs/second.*
    3. Evidence of a personally signed and dated informed consent and assent (where appropriate) document indicating that the subject and a legally acceptable representative/parent(s)/legal guardian have been informed of all pertinent aspects of the study.
    4. Subjects and their legal guardians who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Subjects will be required to provide assent in compliance with local regulations and IRB requirements.
    5. Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to signing informed consent. There should be no significant change (>0.2 mg/kg) in dosage or dose regimen (not related to body weight change) for at least 3 months immediately prior to signing the informed consent and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
    6. Adequate hepatic and renal function on screening laboratory assessments:
    •GGT ≤upper limit of normal (ULN).
    •Alkaline phosphatase ≤ULN.
    •Total Bilirubin ≤ULN.
    •Serum Albumin≥LLN.
    •Serum creatinine ≤ULN.
    7. No underlying disposition for iron accumulation on screening laboratory assessments:
    •Serum Iron≤ULN.
    •Serum Ferritin ≤ULN.
    •% Transferrin Saturation ≤ULN.
    8. No underlying disposition for bleeding disorder on screening laboratory assessments:
    •PT/INR ≤1.25 x ULN.
    •aPTT ≤1.25x ULN.
    9. Iron content estimate on the screening liver MRI is within the normal range as determined by R2* value (R2*≤75 Hz at 1.5 T or R2*≤139 Hz at 3.0 T).

    *Note: The 4 stair climb is expressed as a velocity in the inclusion criteria rather than a time in seconds (>2.5s but ≤12s), in an attempt to reduce the risk of subjects purposefully manipulating their performance at screening in order to enroll.
    E.4Principal exclusion criteria
    1. Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions.
    2. History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study.
    3. Any injury which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior fractures must be fully healed and at least 3 months from injury date.
    4. Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease.
    5. Compromised cardiac function (left ventricular ejection fraction <60% as determined on a screening cardiac MRI or echocardiogram). Subjects may be receiving ACE (angiotensin-converting-enzyme) inhibitors or beta blockers; however they must have initiated treatment more than 3 months prior to screening to ensure stable therapy.
    6. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including uncontrolled hypertension), hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
    7. Documented history of iron overload including hemochromatosis, beta thalassemia major, beta thalassemia intermedia or hemolytic anemia.
    8. Unwilling or unable (eg, metal implants, requires sedation) to undergo examination with closed MRI without sedation.
    9. Participation in other studies involving investigational drug(s) (Phases 1-4) for a minimum of 30 days or within 5 half-lives (whichever is longer) prior to signing the informed consent and/or during study participation.
    10. Current or prior treatment with Exon skipping and nonsense mutation targeted therapies.
    11. Current or prior treatment within the past 3 months with androgens or human growth hormone.
    12. Current treatment with immunosuppressant therapies (other than glucocorticoid steroids), aminoglycosides (eg, gentamicin), multi-vitamins with iron and iron supplements and other investigational therapies.
    13. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein.
    14. Have suicidal ideation and behavior associated with actual intent and/or method and/or plan and/or action (eg, self-harming behaviors) in the past 6 months based on the Columbia-Suicide Severity Rating Scale (C-SSRS Children’s Baseline/Screening Appendix 1) or at baseline (C-SSRS Children’s Since Last Visit Appendix 2).
    15. Subjects who, in the opinion of the investigator, are biologically capable of having children and are sexually active who are unwilling or unable to use a condom to prevent potential transfer of exposure to drug through semen; male subjects of childbearing potential, with their female partners at risk for pregnancy, who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol (in addition to the condom to prevent potential transfer of drug through semen) for the duration of the study and through completion on final study visit.
    16. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are related to Pfizer employees directly involved in the conduct of the study.
    17. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

    Note: Screening laboratory tests with results considered by the investigator to be transient and inconsistent with the subject’s clinical condition may be repeated once during the screening period for confirmation of eligibility.
    E.5 End points
    E.5.1Primary end point(s)
    Safety:
    - Incidence of dose limiting or intolerability treatment related AEs by Week 49.
    - Incidence, severity and causal relationship of treatment emergent AEs (TEAEs) and withdrawals due to TEAEs by Week 49.
    - Incidence and magnitude of abnormal laboratory findings (clinical laboratory tests [hematology, chemistry, GGT, PT, aPTT, creatine kinase, amylase, serum ferritin,
    serum iron, Total Iron Binding Capacity (TIBC), % transferrin saturation, hormone [luteinizing hormone [LH], follicle stimulating hormone [FSH], thyroxine [T4],
    thyroid stimulating hormone [TSH], fecal occult and urinalysis) by Week 49.
    - Abnormal and clinically relevant changes in liver MRI by Week 45 and physical examinations (including nose and throat mucosal exam and Tanner stage), weight, vital signs, ECG, cardiac MRI or echocardiogram measured LVEF (and other exploratory cardiac endpoints), DXA (bone mineral density), x-ray (bone age) and C-SSRS parameters by Week 49. Cardiac MRI with gadolinium is the preferred method for cardiac imaging. If the subject has a
    contraindication to gadolinium, cardiac MRI without gadolinium will be acceptable. Echocardiogram may be substituted if it is not possible to perform cardiac MRI or if
    use of echocardiogram is dictated by the local standard of care.

    Efficacy:
    - Mean change from baseline on the 4 stair climb (4SC) as compared to placebo by Week 49.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 49
    E.5.2Secondary end point(s)
    Strength and Function:
    - Mean change from baseline as compared to placebo on function tests including, Forced Vital Capacity (FVC), Northstar Ambulatory Assessment (NSAA), range of
    motion (ROM), Performance of Upper Limb (PUL), 6MWD at Week 17, 33, 49, 65, 81 and 97. Mean change from baseline as compared to placebo on the 4 SC at Week 17, 33, 65, 81 and 97.
    - Mean change from baseline as compared to placebo on muscle strength by myometry and the modified Medical Research Council [MRC] scale at Week 17, 33, 49, 65, 81
    and 97.

    Pharmacodynamic:
    - Mean percent change as compared to placebo in muscle volume as measured on MRI by Week 17, 33, 49, 65, 81 and 97.
    - Noncompartmental GDF-8 parameters such as AUCt(GDF-8), AUCt,ss(GDF-8), CGDF-8(0), Cmax,ss(GDF-8), Tmax(GDF-8), Ctrough,ss(GDF-8), and Css,av (GDF-8), may be determined.

    Pharmacokinetic:
    - All subjects receiving active drug: Cmax, Tmax, and Ctrough for all visits with PF-06252616 dosing.
    - All subjects receiving active drug in Period 1 followed by placebo in Period 2 (Sequence 2): terminal t½ for Visit 19 (last dose in Period 1) using concentration data from samples collected during placebo treatment in Period 2.
    - Subjects with additional PK sampling receiving active drug in Period 1: AUCt and Cav for Visits 3, 9, and 15 (first dose of each dose escalation level); AUCt, Cav, and CL for Visits 7, 13, and 19 (last dose of each dose escalation level); for subjects in Sequence 2, also Vss for Visit 19.

    Immunogenicity:
    Incidence of ADA and neutralizing antibody (NAb) development by Week 97.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 17, 33, 49, 65, 81 and 97.
    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 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) 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    Italy
    Japan
    United Kingdom
    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 years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months3
    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 Yes
    F.1.1Number of subjects for this age range: 105
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 105
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    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 No
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Boys aged 6 to <10 years old with Duchenne's Muscular Dystrophy
    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 16
    F.4.2.2In the whole clinical trial 105
    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)
    Patients who withdraw from or complete the trial will go back onto the standard of care they were receiving before the trial, as determined by the treating physician. Upon establishing safety and efficacy in Study B5161002, subjects who complete this study may be invited to participate in an open label extension study.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation TREAT-NMD, The University of Newcastle upon Tyne
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-03-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-02-04
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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