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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2005-005358-27
    Sponsor's Protocol Code Number:ASMAB1
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-04-10
    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 ConcernedUK - MHRA
    A.2EudraCT number2005-005358-27
    A.3Full title of the trial
    Efficacy of Rituximab (Mabthera) in active ankylosing spondylitis: a clinical and magnetic resonance imaging study
    A.3.2Name or abbreviated title of the trial where available
    Rituximab in AS
    A.4.1Sponsor's protocol code numberASMAB1
    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 SponsorUniversity Hospital of North Staffordshire
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    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 Information not present in EudraCT
    D.2.1.1.1Trade name MabThera 500
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 Concentrate 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.3.11 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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Ankylosing spondylitis (AS) is an inflammatory condition primarily affecting the spine. The disease may remain symptomatic and progressive life-long. It is part of the family of spondyloarthropathies which also comprises psoriatic arthritis, reactive arthritis and enteropathic arthritis.
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This study is a single centre, 12 month open label proof of concept study, to determine the efficacy of Rituximab (Mabthera), a B cell depleting chimeric monoclonal antibody in Ankylosing Spondylitis (AS). Ten patients with AS according to the New York modified criteria, will be infused with Rituximab. The primary outcome of response to Mabthera treatment will be change in spinal and sacroiliac enthesitis/osteitisbe assessed by MRI scans of the sacroiliac joints and lumbar spine at 0 and 3 months.
    The Haywood Hospital rheumatology unit already has experience using Rituximab in rheumatology patients both within clinical trials and on a clinical need named patient basis.
    E.2.2Secondary objectives of the trial
    Secondary outcomes will include changes before and after treatment in Bath AS Disease Activity Index (BASDAI), Bath AS functional Index (BASFI), Bath AS Metrology Index (BASMI), SF-36, ASQoL and ASQ (AS quality of life), 66 swollen joint count, MASES enthesitis score, CRP/ESR and a broad screen of cytokines linked to AS disease activity including IL-1, IL-6, TNF-α, TGFβ1, VEGF, M-CSF, IFNγ and MMP-3.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    Patients with AS according to the New York modified criteria attending Haywood Hospital, Stoke-on-Trent
    Age between 18-70 years old
    Receiving a stable dose of NSAID for at least 1 month
    Patients willing and able to give informed consent and to comply with the requirements of the protocol.
    Bath AS disease activity (BASDAI) index > 4 (on a scale of 0-10)
    Nocturnal and total back pain visual analogue scale (0-100mm) over 40mm
    Acute inflammatory response (C-reactive protein (CRP) > 10mg/L)
    Failure to respond to at least one non-steroidal anti inflammatory drugs (NSAID)
    If the patient is of reproductive potential (males and females), then they must be using a reliable means of contraception (e.g. contraceptive pill, intrauterine device, physical barrier)
    E.4Principal exclusion criteria
    General
    Contraindications to MRI
    Bone/joint surgery within 8 weeks prior to screening or joint surgery planned within 36 weeks trial entry
    Rheumatic autoimmune disease other than AS
    Psoriasis
    Inflammatory bowel disease
    Excluded previous/concomitant therapies
    Current or previous anti-TNF-α therapy
    Oral prednisolone dose above 10mg daily
    Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti CD-3, anti CD-19)
    Previous treatment within 6 months with iv γ-globulin or Prosorba® Column
    Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit or during the trial.
    General safety
    History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
    Significant cardiac or pulmonary disease
    Known significant uncontrolled concurrent diseases such as renal, hepatic, nervous system, endocrine or gastrointestinal disorders
    Known active bacterial, viral, fungal (excluding fungal infections of the nails beds), mycobacterial or other infections, or any major episode of infection requiring hospitalisation within 4 weeks of screening
    History of significant recurrent infections
    Primary or secondary immunodeficiency
    History of cancer. Including solid tumours and haematological malignancies (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
    Pregnant or lactating females
    History of alcohol, drug or chemical abuse within 6 months of screening
    Lack of peripheral venous access
    Intolerance or contraindications to oral or iv corticosteroids
    Laboratory Criteria
    Serum creatinine > 140umol/L
    Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) > 2.5 times upper limit of normal
    Platelet count < 100 109/L
    Haemoglobin < 8.5 g/dL
    Neutrophils < 1.5 x 103/μL
    Levels of IgG and IgM below 5.65 and 0.55 mg/mL respectively
    E.5 End points
    E.5.1Primary end point(s)
    To determine the efficacy of Rituximab (Mabthera), a B cell depleting chimeric monoclonal antibody in Ankylosing Spondylitis (AS). The primary outcome of response to Mabthera treatment will be change in spinal and sacroiliac enthesitis/ osteitis and using magnetic resonance imaging (MRI) comparing the score of enthesitis in spine at 0 and 3 months.
    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 No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    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 No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    E.8.2.3Other No
    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 No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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 end of the trial will occur 12 months following the entry of the last patient into the trial. At this point a final MRI will be performed to assess long term response in terms of suppression of MRI enthesitis/osteitis.
    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 months4
    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 months4
    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.1.3Elderly (>=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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 10
    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)
    No additional treatment or care over and above that normally given for ankylosing spondylitis once subjects end their participation in the trial.
    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 Decision2006-06-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-07-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2009-07-08
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