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    Summary
    EudraCT Number:2008-002046-27
    Sponsor's Protocol Code Number:OFA110867
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-07-15
    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 ConcernedFrance - ANSM
    A.2EudraCT number2008-002046-27
    A.3Full title of the trial
    OFA110867 : Clinical phase I/IIA study of subcutaneous administration of Ofatumumab in Rheumatoid Arthritis patients on stable dose Methotrexate
    A.4.1Sponsor's protocol code numberOFA110867
    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 SponsorGlaxoSmithKline Research & Development Ltd
    B.1.3.4CountryUnited Kingdom
    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 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 nameOfatumumab
    D.3.2Product code GSK1841157
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeGSK1841157
    D.3.9.3Other descriptive nameHuMax-CD20
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 typeHuman monoclonal antibody
    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 placeboInjection*
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid Arthritis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part A
    To characterize the safety & tolerability of ofatumumab administered as a single subcut dose in patients with rheumatoid arthritis.
    Part B
    To characterize the PK/PD relationship following repeat subcut. administration of Ofatumumab in patients with rheumatoid arthritis. The PK/PD relationship will include evaluation of the time to repletion of CD-19+ peripheral blood B-cells (to <95% depletion from baseline and/or above LLQ) in order to predict the minimum dose interval required for maintenance of >95% depletion of peripheral blood B-lymphocytes in patients with rheumatoid arthritis.
    E.2.2Secondary objectives of the trial
    Part A-Key secondary objectives
    1) To identify and characterize requirement for pre-medication with systemic steroids in association with subcut ofatumumab in patients with rheumatoid arthritis.
    2) To explore the pharmacodynamic dose-response curve for subcut ofatumumab.
    3) To determine the minimum dose of ofatumumab that results in target level of depletion of peripheral blood B- lymphocytes after single subcut. administration. Target level is defined as >95% or to below LLQ, as measured by change from baseline at week 4 and/or the median value across weeks 2-4.
    4) To characterize the PK/PD relationship following single subcut. dose of ofatumumab.
    Part B Key secondary objectives
    1) To characterize the safety & tolerability of ofatumumab administered as two subcut. doses.
    2) To determine the observed time to re-population of CD-19+ peripheral blood B-lymphocytes (cell counts <95% depletion or above LLQ) following repeat dose subcut. administration of ofatumumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female aged ≥ 18 years.
    2. A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least six months duration from diagnosis at screening.
    3. Positive screening for Rheumatoid Factor and/or anti-CCP.
    4. Subjects must be treated with MTX, 7.5-25 mg/week, for at least 12 weeks prior to Visit 2, with the last 4 weeks prior to Day 2 at a stable dosage.
    Patient must be willing to receive folic acid.
    5. Body mass index (BMI) < 35kg/m2 (inclusive).
    6. A female subject is eligible to participate if she is of child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until one year after the last dose of Ofatumumab.
    7. Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until one year after the last dose of Ofatumumab.
    8. QTcB or QTcF < 450 msec.
    9. Chest x-ray is negative for any finding associated with an acute or chronic lung infection at screening.
    A chest X-ray with postero-anterior projections and, if indicated, lateral projections, taken within 12 weeks prior to Visit 1, may be used. Only if clinically warranted should the x-ray be repeated at screening.
    10. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
    11. Following receipt of verbal and written information about the study, the subject must provide signed informed consent before any study related activity including wash-out of other drug products is carried out.
    France: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

    Additional inclusion criteria for Part B
    1. Active disease at the time of screening and baseline with a DAS28 score ≥3.2 (based on ESR) despite stable dose of methotrexate (MTX), 7.5-25mg/week.
    E.4Principal exclusion criteria
    1. Subjects with a history of a rheumatic autoimmune disease other than RA (except secondary Sjögren's syndrome), significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome).
    2. Previous exposure to biologic cell depleting anti-rheumatic therapies, including investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, anti-CD52.
    3. Exposure to etanercept < 4 weeks, infliximab or adalimumab < 8 weeks, or abatacept or anakinra < 12 weeks prior to visit 2.
    4. Received any of the following treatments within 4 weeks prior to Visit 2:
    • Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies)
    • Glucocorticoid unless given in doses equivalent to ≤ 10 mg of prednisolone /day
    • Intra-articular, i.m. or IV corticosteorids
    • Live/attenuated vaccinations
    • Cyclosporine
    • Azathioprine
    • Penicillamine
    5. Exposure to sulfasalazine within 6 weeks prior to Visit 2.
    6. Exposure to Hydroxychloroquine or leflunomide within 12 weeks prior to Visit 2 unless the subject who has received leflunomide has also completed peroral cholestyramine treatment for washout according to locally accepted clinical practices.
    7. Exposure to gold therapy ≤ 12 weeks prior to Visit 2.
    8. Exposure to IV immunogammaglobulins ≤ 24 weeks prior to Visit 2
    9. Past or current malignant melanoma.
    10. Past or current malignancy, except for:
    • Cervical carcinoma Stage 1B or less
    • Non-invasive basal cell skin carcinoma
    • Other cancer with a complete response duration of > 5 years
    11. Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, renal infection, chest infection with bronchiectasis, tuberculosis and active hepatitis B and C.
    • Screening for TB will be done in accordance with local guidelines including Mantoux testing, and if necessary follow-up with QuantiFERON testing for patients whose history of immunization with BCG cannot be documented.
    • Patients with a negative test OR a positive Mantoux test and a negative QFT-G test are eligible for inclusion into the study.
    • Patients with a positive Mantoux test without QFT-G negativity are excluded. Additionally, patients with documented BCG vaccination will be exempted from the Mantoux test assessment.
    12. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure, known QT abnormalities, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.
    13. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease.
    14. History of significant cerebrovascular disease.
    15. Known HIV positive.
    16. Screening laboratory values (according to central laboratory):
    • Hemoglobin < 5.6 mmol/L (9.0 g/dL)
    • CD19+ B-cell count < 0.1 x 109/L
    • Neutrophils < 2 x 109/ L
    • Platelets < 100 x 109/ L
    • Serum IgG < lower limit of normal
    • S-ALAT > 3 times the upper limit of normal
    • S-AST > 3 times the upper limit of normal
    • S-ALP > 2 times the upper limit of normal
    • S-creatinine > 133 µmol/L (1.5 mg/dL)
    17. Positive serology for hepatitis B (HB) defined as:
    • Positive test for HBsAg.
    If negative, Hep B serology negativity will be confirmed by:
    • Negative serology to anti-HBc. Patients who are positive for Hepatitis B core antibody are excluded.
    • Negative serology to HB surface antibody.
    Hepatitis B surface antibody positivity without core antibody positivity indicates vaccination against Hepatitis B and is not exclusionary.
    18. Positive test for anti-hepatitis C antibody.
    19. Positive plasma / white cell JC Virus (JCV) PCR (either compartment)
    20. Known hypersensitivity to components of the investigational medicinal product or MTX.
    21. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
    22. Subjects who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks or 5 half-lives (whichever is longer) prior to screening.
    23. Current participation in any other interventional clinical study.
    24. Subjects known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
    25. The subject has a positive pre-study drug screen with positive results for amphetamines, cocaine or cannabinoids.
    26. Breast feeding women or women with a positive pregnancy test at screening.
    27. Unwillingness or inability to follow the procedures outlined in the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Part A:
    • Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
    Part B:
    • PK/PD parameters including time to recovery of CD-19+ peripheral blood B- lymphocytes to above LLQ (and/or <95% depletion) following repeat subcutaneous dose of Ofatumumab.
    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 Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    PK/PD dose ranging study
    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 Yes
    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 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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
    End of trial will be last patient to complete Visit 19 in Part B. Patients will be followed up every 12 weeks until B cells and IgM return to LLN or baseline. CSR will be prepared based on the data through Visit 19 in Part B. An addendum to the CSR will be prepared once all patients have completed the follow up period. It is anticipated follow up period may be extended as long as 2 years from Visit 19.
    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 months7
    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 months7
    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 state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 35
    F.4.2.2In the whole clinical trial 70
    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 Decision2008-09-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-07-31
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-04-22
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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