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    Summary
    EudraCT Number:2004-002815-10
    Sponsor's Protocol Code Number:C0168T67
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-07-10
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2004-002815-10
    A.3Full title of the trial
    Multicenter, Randomized, Double-Blind, Active-Controlled Trial Comparing REMICADE® (infliximab) and REMICADE® plus Azathioprine to Azathioprine in the Treatment of Patients with Crohn’s Disease Naive to both Immunomodulators and Biologic Therapy (Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease) SONIC
    A.3.2Name or abbreviated title of the trial where available
    SONIC
    A.4.1Sponsor's protocol code numberC0168T67
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCentocor B.V.
    B.1.3.4CountryNetherlands
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Remicade
    D.2.1.1.2Name of the Marketing Authorisation holderCentocor 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.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNinfliximab
    D.3.9.3Other descriptive nameChimeric IgG1 monoclonal antibody
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal antibody
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Imuran
    D.2.1.1.2Name of the Marketing Authorisation holderPrometheus Laboratories Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNazathioprine
    D.3.9.3Other descriptive name6-[(methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboPowder for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule*
    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
    moderate to severe Crohn’s Disease
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.1
    E.1.2Level LLT
    E.1.2Classification code 10011401
    E.1.2Term Crohn's disease
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the Main Study will be to compare the efficacy of infliximab + placebo capsules and infliximab combined with azathioprine (AZA) to azathioprine + placebo infusions in the treatment of patients with moderate-to-severe Crohn’s disease.

    The primary objective of the Study Extension will be to evaluate the long-term efficacy and safety of infliximab and/or AZA through week 54.
    E.2.2Secondary objectives of the trial
    1) To assess the effect of infliximab and/or AZA on complete mucosal healing in patients with Crohn’s disease.

    2) To assess the corticosteroid-sparing abilities of therapy with infliximab and/or AZA in patients with moderate-to-severe Crohn’s disease.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Full title: SONIC Open-Label Extension Study
    Date: 17 January 2007, 5th amendment of original SONIC protocol
    The primary objective is to assess the long-term efficacy of infliximab maintenance therapy in achieving and/or maintaining remission at week 100 (approximately 2 years) after enrollment in SONIC OLE in patients with Crohn’s disease. Patients in clinical remission will be defined as those with a CDAI < 150.
    The secondary objectives are:
    1. To evaluate the benefits of long-term maintenance treatment with infliximab.
    2. To assess the rate of discontinuation from long-term maintenance treatment with
    infliximab.
    3. To evaluate health-related quality of life and pharmacoeconomic benefits of long-term maintenance treatment with infliximab. Safety will be assessed by analysis of adverse events and serious adverse events throughout the study.
    E.3Principal inclusion criteria
    1) Are considered eligible according to the following tuberculosis (TB) screening criteria:
    a. Have no history of latent or active TB prior to screening.
    b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
    c. Have had no recent close contact with a person with active TB.
    d. Within 1 month prior to the first administration of study agent have a negative tuberculin skin test.
    e. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB. For European Countries Only: If according to country-specific guidelines lateral views are not done, having only the posterior-anterior view is acceptable.
    2) Are 21 years of age or older at the time of the first study infusion (Week 0); may be male or female.
    3) Have a CDAI score of ≥ 220 and ≤ 450.
    4) Have Crohn’s disease of at least 6 weeks duration, with colitis, ileitis, or ileocolitis, confirmed by radiography or endoscopy. Single or multiple draining fistulas may be present provided there is no evidence of active fistula-related abscess.
    5) Are EITHER:
    a. Corticosteroid-dependent (ie, patients who become symptomatic after a decrease in corticosteroid dose such that they have a CDAI ≥ 220 [budesonide alone does not qualify as a corticosteroid for the purpose of this criterion]), OR
    b. Are being considered for their second (or greater) course of oral systemic corticosteroids (prednisone or equivalent), (budesonide alone does not qualify as a corticosteroid for the purpose of this criterion) for active Crohn’s disease within the past 12 months, OR
    c. Are 5-ASA failures (ie, patients who have not had an adequate response to at least a 4-week course of 5-ASA or sulfasalazine (ie, 2.4 g/day 5-ASA or equivalent in sulfasalazine [Germany only: 3 to 4 g/day 5-ASA or equivalent in sulfasalazine] for at least 4 weeks), OR
    d. Are budesonide failures (i.e., patients who have not had an adequate response to a course of budesonide ≥6 mg/day [Germany only: ≥9 mg/day] for at least 4 weeks). Budesonide failures who are 5-ASA-naive are eligible for this study.
    6) Are able to adhere to the concomitant medication requirements as described in the protocol, section 4.1: Inclusion Criteria (under bullet six).
    7) Are able to adhere to the study visit schedule and other protocol requirements.
    8) Are capable of providing written informed consent. Written informed consent must be obtained prior to performing any study-related procedures.
    9) Women of childbearing potential and all men who are (or become) sexually active must use adequate birth control measures (eg, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the study and must continue such precautions for 6 months after receiving the last study agent infusion.
    10) The screening laboratory tests must meet the following criteria:
    a. Hemoglobin > 8.5 g/dL
    b. WBC count > 3.5 billion cells/L
    c. Neutrophils > 1.5 billion cells/L
    d. Platelets >100 billion cells/L
    e. AST and ALT levels must be within 2 times the ULN for the laboratory conducting the test. Alkaline phosphatase levels must be within 3 times ULN for the laboratory conducting the test.

    For the OLE extension the following criteria are applicable:
    1. Must have completed the week 50 visit in the Main study.
    2. Have a CDAI score of ≤450 at the time of the first infusion.
    3. Are able to adhere to the concomitant medication requirements as detailed in
    Section 7 of this Appendix.
    4. Are able to adhere to the SONIC OLE visit schedule (see Section 6 of this
    Appendix).
    5. Are capable of providing written informed consent. Written informed consent
    must be obtained prior to performing any procedures in SONIC OLE.
    6. Women of childbearing potential and all men who are (or become) sexually
    active must use adequate birth control measures (eg, oral contraceptives,
    intrauterine device, barrier method with spermicide, or surgical sterilization)
    throughout the study and must continue such precautions for 6 months after
    receiving the last infliximab infusion.
    7. The screening laboratory tests must meet the following criteria:
    a. Hemoglobin > 8.5 g/dL (5.3 mmol/L)
    b. White blood cell (WBC) count > 3.5 x 109 cells/L
    c. Neutrophils > 1.5 x 109 cells/L
    d. Platelets >100 x 109 cells/L
    e. ALT levels must be within 5 times the ULN for the laboratory
    conducting the test.
    E.4Principal exclusion criteria
    1)Have local manifestations of CD like strictures, active fistula-related abscesses, or other complications for which surgery might be indicated or might preclude utilization of CDAI to assess response to therapy If an abscess has been present previously, at least 6 weeks must have elapsed between drainage of the abscess and screening.
    2)Have had intra-abdominal surgery within 6 months prior to screening.
    3)Have received treatment with parenteral nutrition within 6 weeks of screening.
    4)Have an ostomy or stoma.
    5)Have known severe fixed symptomatic stenosis of the large or small intestine.
    6)Are pregnant, nursing, or planning pregnancy during the trial or within 6-month period thereafter.
    7)Have shown an hypersensitivity response, including anaphylaxis, to an immunoglobulin product.
    8)Have an allergy to murine proteins or other chimeric proteins.
    9)Have received within 3 months prior to screening or are expected to receive any live virus or live bacterial vaccinations during the trial or up to 3 months after the last administration of study agent.
    10)Have had a serious infection, or been hospitalized for an infection, or treated with intravenous antibiotics for an infection within 2 months prior to screening.
    11)Have a history of latent or active granulomatous infection.
    12)Have had a BCG vaccination within 12 months of screening.
    13)Have had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to screening.
    14)Have a chest radiograph within 3 months prior to randomization that shows an abnormality suggestive of a malignancy or current active infection, including TB.
    15)Are considered ineligible according to the TB eligibility assessment, screening and early detection of reactivation rules defined in the protocol.
    16)Have current active hepatitis B or a history of hepatitis C infection.
    17)Have HIV infection.
    18)Have signs, symptoms of or a history of SLE; severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases.
    19)Have a transplanted organ.
    20)Have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, like lymphadenopathy of unusual size or location or splenomegaly.
    21)Have any known malignancy or history of malignancy within the 5-year prior to screening.
    22)Have multiple sclerosis or other central demyelinating disorder.
    23)Have had a chronic or recurrent infectious disease including but not limited to chronic renal infection; chronic chest infection; sinusitis; recurrent urinary tract infection; open, draining, or infected skin wound or ulcer.
    24)Have a concomitant illness that could interfere with the patient’s participation in the trial.
    25)Have used any investigational drug within 30 days prior to screening, or within 5 half-lives of the investigational agent, whichever is longer.
    26)Are participating in another trial using an investigational agent, procedure, or device during participation in this trial.
    27)Have previously participated in 3 or more investigative trials in CD within 5 years prior to screening. Patients participating in the TREAT registry must discontinue from the registry before enrolling in SONIC.
    28)Have a history of substance abuse within the previous 3 years, history of noncompliance to medical regimens, or other condition/circumstance that could interfere with the patient’s adherence to protocol requirements.
    29)Have a concomitant diagnosis or any history of CHF.
    30)Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
    31)Are known to have a homozygous mutant or heterozygous thiopurine methyltransferase (TPMT) phenotype.TPMT phenotype should not be assayed in patients within 90 days of receipt of a red blood cell transfusion.
    32)Weigh more than 140 kg.
    33)Have previously received natalizumab.
    34)Have recently close contact with a person with active TB.
    35)Positive stool culture for enteric pathogens, pathogenic ova, or parasites, or Clostridium difficile toxin.
    For the SONIC OLE extension:
    1.Are deemed ineligible according to the TB screening criteria defined in the protocol.
    2.Have experienced an adverse event during or within 1 hour following the study agent infusion in the SONIC Main study, resulting in bronchospasm with wheezing, dyspnea requiring ventilatory support, or hypotension with a >40 mm Hg decrease in systolic blood pressure that is associated with symptoms.
    3.Have had a delayed hypersensitivity reaction.
    4.Are pregnant, nursing, or planning pregnancy during the OLE or within the 6-month period thereafter.
    5.Have been unblinded to study treatment in the SONIC Main study.
    6.Have been diagnosed with a malignancy.
    7.Have previously received any other TNF-a blocking agent or any other biological drug.
    8.Have required or requires a Crohn’s disease-related surgery.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint will be the proportion of patients in corticosteroid-free clinical remission, ie, patients with a CDAI of less than 150 who have not been taking oral systemic corticosteroids (prednisone or equivalent) for at least 3 weeks and have not been taking budesonide at a dose greater than 6 mg/day for at least 3 weeks at week 26.

    The primary end point of the SONIC OLE extension wil be the proportion of patients in clinical remission, ie, patients with a CDAI of less than 150, at the week 100 visit of the SONIC OLE.
    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 Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of Life
    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.8.1.7.1Other trial design description
    The OLE extension will be an open label trial
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 EEA69
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    N.A.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 234
    F.4.2.2In the whole clinical trial 500
    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)
    N.A.
    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 Decision2005-05-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-07-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2009-12-11
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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