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    The EU Clinical Trials Register currently displays   41189   clinical trials with a EudraCT protocol, of which   6743   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2006-002306-64
    Sponsor's Protocol Code Number:Ritux-AS-01
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-10-04
    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 ConcernedGermany - PEI
    A.2EudraCT number2006-002306-64
    A.3Full title of the trial
    Open label clinical trial with Rituximab (MabThera ®) in Ankylosing Spondylitis - Extension of open label trial: Re-Treatment of patients who have shown response to first course of Rituximab
    A.3.2Name or abbreviated title of the trial where available
    Ritux-AS-01
    A.4.1Sponsor's protocol code numberRitux-AS-01
    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 SponsorCharité Universitaetsmedizin
    B.1.3.4CountryGermany
    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 Yes
    D.2.1.1.1Trade name Rituximab/ Mabthera
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Ltd.
    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.3.1Product nameMabThera
    D.3.2Product code Ro45-2294
    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.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNrituximab
    D.3.9.1CAS number 174722-31
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Information not present in EudraCT
    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
    Moderate to severe ankylosing spondylitis who have had an inadequate response to or do not tolerate conventional therapy including NSAIDs, DMARDs and TNF alpha inhibitors

    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
    To evaluate the efficacy and safety of rituximab when added to NSAIDs and/ or methotrexate both for TNFalpha inhibitor naïve or TNFalpha inhibitor failure patients with moderate to severe ankylosing spondylitis.

    Primary endpoint: Efficacy Evaluation in week 24 and until study end: ASAS 20 in AS patients naïve to TNFalpha inhibitors as well as in AS patients with previous therapy with TNFalpha inhibitors.

    Patients who have shown good response to initial treatment with Rituximab (good response defined as reaching ASAS20 criteria on two consecutive visitis between week 12 and week 24) are eligible for a second course of Rituximab if they show a flare of their disease (flare defined as a 1.5-point-worsening of the BASDAI score between week 24 and 48 compared to the best BASDAI score between week 12 and 24).

    Primary endpoint for patients who are re-treated: ASAS20 response at week R-24.
    E.2.2Secondary objectives of the trial
    Secondary endpoints:

    Safety Evaluations: Adverse events, vital signs, physical examination results, and clinical laboratory values until week (R-) 48.


    Efficacy Evaluations: ASAS 40 response, ASAS criteria for partial remission, 20%, 50% and 70% improvement of disease activity (BASDAI), improvement of BASMI, BASFI, SF-36, number of swollen joints, number of enthesitic regions (Maastricht Index), regression of inflammation (CRP, ESR), patients– and physicians global assessment, general and nocturnal pain, EQ-5D, socioeconomic questionnaire, MRI for acute and chronic lesions at 24 weeks and at 48 weeks compared to screening for patients receiving course 1 and MRI for acute and chronic lesions at week R-24 and R-48 for patients receiving course 2 (re-treatment), B cell and T cell analysis at weeks (R-) 4, (R-) 12, (R-) 24 and (R-) 48 for patients receiving course 1 (or(and) 2.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria:

    - Patients 18 – 65 years of age who have moderate to severe ankylosing spondylitis.

    - Active disease is defined as a BASDAI score of > = 4 plus a back pain score (BASDAI question 2) of >= 4 despite concurrent NSAID therapy, or intolerance to NSAIDs

    - If on prednisone, £10 mg per day must be stable for 4 weeks prior to baseline.

    - If on methotrexate, £ 25 mg per week must be stable for 4 weeks prior to baseline

    - Women of child bearing potential must have a negative pregnancy urine test at study baseline and use an adequate, effective method of contraception (such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, vasectomised partner) for a duration of 12 months after stop of rituximab therapy. Sexual active men must use an accepted method of contraception for a duration of 12 months after first administration of rituximab.

    - Willingness and capability to give written informed consent, written consent for data protection (legal requirement in Germany: datenschutzrechtliche Einwilligung) and willingness to participate and to comply with the study

    - Patients are eligible for a second course of rituximab if they: A) in response assessment period= week 12- week 24: have shown a response after the first administration of rituximab; response defined as reaching ASAS20 criteria (compared to screening) on at least two subsequent time points between week 12 and week 24, B) in flare assessment period (starting from week 24- 48): have a flare after they have shown response (as described above): flare defined as having a 1.5-point-worsening of the BASDAI score in comparison to the lowest BASDAI score between week 12 and week 24, and C) have completed week 24 (re-treatment 24 weeks after first administration of rituximab at the earliest)
    E.4Principal exclusion criteria
    Exclusion criteria

    Exclusion criteria related to general health conditions:
    1. Patients with other chronic inflammatory articular disease or systemic autoimmune disease, e.g. Systemic lupus erythematosus, Sjögren’s syndrome, active rheumatoid vasculitis, a history of systemic diseases associated with arthritis, chronic fatigue syndrome
    2. Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms
    3. Primary or secondary immunodeficiency
    4.History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised
    5. A history of pulmonary or cardiac insufficiency, or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome
    6.Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease ( e.g. heart failure class III/IV NYHA, cardiac infarct within last 6 month), nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
    7.Neuropathy that can interfere with quality of life and/or pain assessment.
    8.Patients with a history of a severe psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
    9.History of current evidence of abuse of “hard” drugs (e.g. cocaine/ heroine) or alcoholism
    10.Known hypersensitivity to any component of the product or to murine proteins (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, HCl).
    11.Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test (urine test)
    12.Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier) for up to 12.5 months after first infusion of rituximab
    13.History of alcohol, drug or chemical abuse within 6 month prior to screening
    14.Lack of peripheral venous accessExclusion criteria related to medications
    15.If on leflunomide, leflunomide must have been terminated at least 8 weeks prior to the first rituximab infusion (or ≥ 28 days after 11 days of standard cholestyramine or activated charcoal washout).
    16.If on TNFalpha blocking agent (infliximab, etancercept, adalimumab), the TNFa therapy must have been terminated at least 4 weeks prior to the first rituximab infusion if etanercept was used and at least 8 weeks if infliximab or adalimumab were used
    17.Previous treatment with rituximab or intolerance to rituximab
    18.Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent within the last 4 weeks prior to the first rituximab infusion
    19.Intolerance or contraindication to drugs required for the treatment of the side effects of rituximab (e.g. paracetamol, acetaminophen, diphenhydramine, p.o. and i.v. corticosteroids, anti-emetics or H1 blockers)
    20.Previous treatment with any investigational agent
    21.Previous treatment with i.v. immunoglobulins
    22.Receipt of a live vaccine within 4 weeks prior to treatment
    23.Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visitExclusion criteria related to lab findings
    24.Haemoglobin < 8.5 g/dl
    25.Neutrophil counts < 1.500 / µl
    26.Platelet count < 75.000 / µl
    27.Lower than 1 x 1000/µl lymphopenia for more than three months prior to inclusion.
    28.Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men.
    29.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper limit of normal
    30.Positive HIV, hepatitis B or C serology

    Exclusion criteria related to formal aspects
    31.Patients who participate currently in another clinical trial or patients who participated in another clinical trial during the last 30 days.
    32.Patients who are underage or patients who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG).
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint: Efficacy Evaluation in week 24 and until study end: ASAS 20 in AS patients naïve to TNFalpha inhibitors as well as in AS patients with previous therapy with TNFalpha inhibitors. For patients going into the extension study: ASAS 20 at week R-24.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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
    B and T cell analysis, MRI outcome acute and chronic inflammatory
    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 No
    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 Yes
    E.8.1.7.1Other trial design description
    one-armed open trial
    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 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 concerned2
    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 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
    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 months0
    E.8.9.1In the Member State concerned days0
    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) No
    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 state20
    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 will receive the standard treatment with standard care as needed throughout and after the study. After week 48 an additional or changed treatment is left to the discretion of the investigator.
    Any other specific treatment of the patient after study end is not planned. The investigator will inform the patients about all available standard-of-care treatments and the decision is left to the patient’s and investigator’s discretion.
    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 Decision2006-12-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-12-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2007-07-10
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