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    Summary
    EudraCT Number:2018-002247-28
    Sponsor's Protocol Code Number:MOM-M281-004
    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:2018-12-31
    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 number2018-002247-28
    A.3Full title of the trial
    A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Adults with Generalized Myasthenia Gravis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    To evaluate the efficacy, safety and tolerability of M281 injection for the treatment of patients with Myasthenia gravis, a neuromuscular disease
    A.4.1Sponsor's protocol code numberMOM-M281-004
    A.5.4Other Identifiers
    Name:IND NumberNumber:138975
    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 SponsorMomenta Pharmaceuticals, 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 supportMomenta Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMomenta Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street Address301 Binney Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02142
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrialinfo@momentapharma.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 nameM281 Injection
    D.3.2Product code M281
    D.3.4Pharmaceutical form Solution for injection
    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 INNM281
    D.3.9.1CAS number 2211985-36-1
    D.3.9.3Other descriptive nameM281
    D.3.9.4EV Substance CodeSUB182674
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 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
    Treatment of MG, with an initial focus on patients with gMG treated with M281 injection and evaluation of the expected reduction of circulating levels of antibodies by blocking IgG recycling, including the pathogenic autoantibodies that cause MG, and to ameliorate manifestations of the disease.
    E.1.1.1Medical condition in easily understood language
    Treatment of Myasthenia gravis (neuromuscular disease) to evaluate the safety efficacy and tolerability of M281 Inj. in patients who have insufficient clinical response to ongoing standard therapy.
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10028417
    E.1.2Term Myasthenia gravis
    E.1.2System Organ Class 10029205 - Nervous system 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 evaluate the safety and tolerability of treatment with M281 injection in patients with gMG who have an insufficient clinical response to ongoing, stable standard of care therapy.
    To determine the efficacy of M281 injection for gMG as measured by the change in Myasthenia Gravis – Activities of Daily Living (MG-ADL) score.
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of M281 injection as measured by changes in the Quantitative Myasthenia Gravis (QMG) score and the revised Myasthenia Gravis Quality of Life - 15 Scale (MG-QoL15r).
    To determine the pharmacokinetics (PK) of M281 injection.
    To estimate the pharmacodynamic (PD) activity of M281 injection as measured by effects on total serum immunoglobulin (Ig)G concentrations.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Is a male or female outpatient ≥18 years of age.
    2. Has a documented history of gMG and clinical signs/symptoms of gMG.
    3. Has a documented diagnosis of gMG by a positive serologic test for a gMG-related pathogenic autoantibody (anti-AChR or anti-MuSK autoantibodies), confirmed at Screening, and is on stable therapy for MG. If the patient receives the first dose of M281 before the Screening results are available and the results are subsequently negative, the patient may be replaced.
    4. Has a Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II, III, or IVa at Screening.
    5. Has a QMG score of ≥12 at Screening and Baseline.
    6. If taking a glucocorticosteroid, the patient must provide/obtain documentation showing the dose and regimen has been stable for at least 4 weeks prior to Screening.
    7. If taking an acetylcholinesterase inhibitor, the patient must provide/obtain documentation
    showing the dose and regimen has been stable for at least 2 weeks prior to randomization on Day 1.
    8. If taking statins at Screening, the patient must provide/obtain documentation showing the dose and regimen has been stable for at least 2 months prior to Screening.
    9. If currently receiving immunosuppressants, the patient must provide/obtain documentation showing that the patient has been on the given immunosuppressant for ≥6 months and has been on a stable dose for ≥3 months prior to Screening. Allowed concomitant immunosuppressants are azathioprine, mycophenolate mofetil/ mycophenolic acid, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide.
    10. Has total serum IgG, serum albumin, and serum calcium concentrations within the normal range of the reference laboratory at Screening.
    11. Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol.
    12. Is up to date on all age-appropriate vaccinations as per routine local medical guidelines.
    13. Women of childbearing potential, defined as women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at Baseline. Menopausal women must have an elevated serum follicle-stimulating hormone level (FSH) at Screening; if the FSH is not elevated, they are considered to be of childbearing potential and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline to be eligible.
    14. Women of childbearing potential (including menopausal women who do not have elevated FSH) must agree to remain totally abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a reliable and highly effective method of contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive used in combination with an additional barrier method) during the study and for 30 days after the last study treatment.
    Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
    15. Male patients must agree to remain totally abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a reliable and highly effective method of contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive used in combination with an additional barrier method) to avoid pregnancy of the patient’s partner(s) during the study and for 100 days following the last study treatment, unless the patient provides documentation of a vasectomy at least 6 months prior to Screening. Male patients must also abstain from sperm donation during the study and for 100 days following the last treatment.
    Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
    16. A patient using herbal, naturopathic, and traditional Chinese remedies and ayurvedic and nutritional supplements is eligible if the use of these medications is acceptable to the Investigator. These remedies must be at a stable dose and regimen using the same preparation for ≥2 months prior to Screening.
    17. Is able to understand and voluntarily provide written informed consent to participate in the study and comply with all study procedures.
    E.4Principal exclusion criteria
    1.Has MGFA Class I, IVb, or V disease, or presence of MG crisis (MGFA Class V) at Screening or Baseline, history of MG crisis within 1 month of the Screening visit, or fixed weakness (and/or ‘burnt out’ MG).
    2.Has received rituximab or eculizumab within 12 months prior to Screening.
    3.Has received plasmapheresis, immunoadsorption therapy, or IVIG within 6 weeks prior to randomization on Day 1.
    4.Has a serious or clinically significant infection.
    5.Has a chronic infection.
    6.Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her gMG, including human immunodeficiency virus (HIV) infection, or has a family history of congenital or hereditary immunodeficiency.
    7.Has a positive or equivocal QuantiFERON®-TB Gold test, and/or a known close exposure to family or individuals known to have tuberculosis.
    8.Has had a splenectomy.
    9.Received treatment for malignancy within the 5 years prior to Screening, with the exceptions of properly treated basal or squamous cell carcinoma of the skin or properly treated carcinoma in situ of the cervix.
    10.Has a hypersensitivity to M281 or any constituent of the study drug solution.
    11.Has had a prior severe drug reaction that included shock or severe hypersensitivity.
    E.5 End points
    E.5.1Primary end point(s)
    1. M281 safety will be evaluated in terms of the incidence of AEs compared to placebo.
    2. Change of MG-ADL score for each treatment group from baseline to Day 57. It will be evaluated via dose-response analyses and with mixed-effects model repeated measures (MMRM) analyses.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Dose-respond analyses and MMRM analyses will be performed using data from Day 15, 29, 43 and 57. MMRM analyses will include variables for baseline MG-ADL score, treatment-by-study week interaction, and autoantibody type, with variance-covariance structure assumed as compound symmetry.
    E.5.2Secondary end point(s)
    1. A model-based analysis of total MG-ADL score change from Baseline and difference from placebo in relationship to total serum IgG percent of Baseline and treatment frequency. All five study arms will be included in a simultaneous analysis of total MG-ADL score as a function of total serum IgG (Baseline to Day 57).
    2. A model-based analysis of total MG-ADL score change from Baseline and difference from placebo during the study as a response to percent change in total serum IgG (Baseline to Day 57), for patients positive for anti-AChR antibodies only.
    3. Responder analysis: number of patients with a 2-, 3-, 4-, 5-, 6-, 7-, or ≥8-point improvement in total MG-ADL score from Baseline to Day 57.
    4. Change in total QMG score from Baseline to Day 57.
    5. Change in total MG-QoL15r score from Baseline to Day 57.
    6. Shift in MGFA classification from Baseline to Day 57 for each treatment group.
    7. Change in total serum IgG from Baseline to Day 57 for each treatment group.
    8. Change in total MG-ADL, QMG, and MG-QoL15r scores over time after the last dose.
    9. Responder analysis: number of patients with a 2-, 3-, 4-, 5-, 6-, 7-, or ≥8-point improvement in total QMG score over time after the last dose.
    10. Shift in MGFA classification over time after the last dose.
    11. Change in total serum IgG over time after the last dose.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The model-based analysis of total MG-ADL score change from Baseline, change from placebo will assess a set of monotonic models to define the effect of IgG lowering on MG-ADL changes from baseline to Day 57. The models will be averaged and the effects will be summarized by median IgG lowering for each of the treatment groups. A second analysis will perform the same model-based assessment (from Baseline to Day 57) including only patients positive for anti-AChR antibodies.
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity Assessments, Biomarkers
    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 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.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Belgium
    Canada
    France
    Germany
    Italy
    Poland
    Spain
    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
    The study includes a Screening Period of up to 4 weeks, an 8-week Treatment Period, and an 8-week follow-up period (beginning after the last infusion). Last visit of the patient will take place at Day 113. Total study duration is 20 weeks.
    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 months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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: 36
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 24
    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 No
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 60
    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)
    Upon completion of the study at or on Day 113 patients may have the option to enroll in a separate open-label extension study where they will receive treatment with M281.
    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 Decision2019-02-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-06-25
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