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HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II

Primary Purpose

Arthritis, Rheumatoid

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Part A
Part B
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years Active rheumatoid arthritis according to the American College of Rheumatology of at least six months duration with six or more swollen and six or more tender joints (of 28 joints) and Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/h and/or C-Reactive Protein (CRP) ≥ 10 mg/L (1 mg/dL). Treatment failure to one or more DMARDs. Treatment with methotrexate (7.5-25 mg/wk) for at least 12 weeks and at a stable dose for at least 4 weeks prior to planned start of trial treatment. Exclusion Criteria: Use of DMARDs other than methotrexate. Current or previous (within four weeks of screening) participation in any other clinical trial. Previous exposure to other biological products within 4 weeks prior to planned start of trial treatment, and/or exposure to anti-CD20 antibodies within two years before screening for this trial. Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial. Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy. Past or current malignancy, except for resected cervical carcinoma Stage 1B or less, non-invasive basal cell and squamous cell skin carcinoma, malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years. Chronic or current infectious disease including known or suspected positive serology for HIV, hepatitis B, or hepatitis C. Clinically significant cardiac disease, or history of significant cerebrovascular disease. Significant concurrent, uncontrolled medical condition including, but not limited to: renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease. Breast feeding women, women with a positive pregnancy test at screening, or women of childbearing potential not willing to use adequate contraception during the trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Placebo Comparator

    Arm Label

    Dose ranging

    Parallel Arm RCT

    Arm Description

    A double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A),

    a parallel group part with randomization into one of 4 treatment arms (Part B).

    Outcomes

    Primary Outcome Measures

    To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
    To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment

    Secondary Outcome Measures

    To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion
    To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis
    To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20
    To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 36 & 48 weeks after initiation of treatment
    To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis

    Full Information

    First Posted
    February 14, 2006
    Last Updated
    November 8, 2012
    Sponsor
    GlaxoSmithKline
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00291928
    Brief Title
    HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II
    Official Title
    A Double-blind, Randomized, Placebo Controlled, Dose Escalation, Multi-centerphase I/II Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20antibody, in Patients With Active Rheumatoid Arthritis Who Have Previously Failedone or More Disease Modifying Anti-rheumatic Drugs
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2012
    Overall Recruitment Status
    Completed
    Study Start Date
    February 2005 (undefined)
    Primary Completion Date
    September 2007 (Actual)
    Study Completion Date
    September 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    GlaxoSmithKline

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this trial is primarily to investigate the safety profile of HuMax-CD20 in patients with active RA. Furthermore, the trial is designed to identify the dose levels to be used in future trials (based on evaluations of safety, pharmacokinetics and ACR and DAS responses).
    Detailed Description
    This trial consists of a double-blind, placebo controlled, dose escalation part with randomization to trial treatment within each of three sequential cohorts (Part A), and a parallel group part with randomization into one of four treatment arms (Part B). Patients in Parts A and B will receive two infusions of either HuMax-CD20 (300 mg, 700 mg, or 1000 mg) or placebo and will be followed for safety, efficacy, and pharmacokinetic measurements for 24 weeks. Hereafter patients will be followed every 12 weeks until B-cells (CD19+ cells) have returned to baseline levels. For patients in Part B, the follow-up visits at 36 and 48 weeks after initial trial treatment (Follow-up Visits 1 and 2) will include additional measurements of safety and efficacy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Arthritis, Rheumatoid

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    201 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Dose ranging
    Arm Type
    Placebo Comparator
    Arm Description
    A double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A),
    Arm Title
    Parallel Arm RCT
    Arm Type
    Placebo Comparator
    Arm Description
    a parallel group part with randomization into one of 4 treatment arms (Part B).
    Intervention Type
    Drug
    Intervention Name(s)
    Part A
    Intervention Description
    Part A Cohort 1: HuMax-CD20 300 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 2: HuMax-CD20 700 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 3: HuMax-CD20 1000 mg at Days 0 and 14 or Placebo at Days 0 and 14
    Intervention Type
    Drug
    Intervention Name(s)
    Part B
    Intervention Description
    Part B Group 1: HuMax-CD20 300 mg at Days 0 and 14 Group 2: HuMax-CD20 700 mg at Days 0 and 14 Group 3: HuMax-CD20 1000 mg at Days 0 and 14 Group 4: Placebo at Days 0 and 14
    Primary Outcome Measure Information:
    Title
    To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
    Time Frame
    24 weeks
    Title
    To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment
    Time Frame
    24 weeks
    Secondary Outcome Measure Information:
    Title
    To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion
    Time Frame
    24 weeks
    Title
    To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis
    Time Frame
    24 weeks
    Title
    To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20
    Time Frame
    24 weeks
    Title
    To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 36 & 48 weeks after initiation of treatment
    Time Frame
    48 weeks
    Title
    To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis
    Time Frame
    24 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years Active rheumatoid arthritis according to the American College of Rheumatology of at least six months duration with six or more swollen and six or more tender joints (of 28 joints) and Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/h and/or C-Reactive Protein (CRP) ≥ 10 mg/L (1 mg/dL). Treatment failure to one or more DMARDs. Treatment with methotrexate (7.5-25 mg/wk) for at least 12 weeks and at a stable dose for at least 4 weeks prior to planned start of trial treatment. Exclusion Criteria: Use of DMARDs other than methotrexate. Current or previous (within four weeks of screening) participation in any other clinical trial. Previous exposure to other biological products within 4 weeks prior to planned start of trial treatment, and/or exposure to anti-CD20 antibodies within two years before screening for this trial. Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial. Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy. Past or current malignancy, except for resected cervical carcinoma Stage 1B or less, non-invasive basal cell and squamous cell skin carcinoma, malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years. Chronic or current infectious disease including known or suspected positive serology for HIV, hepatitis B, or hepatitis C. Clinically significant cardiac disease, or history of significant cerebrovascular disease. Significant concurrent, uncontrolled medical condition including, but not limited to: renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease. Breast feeding women, women with a positive pregnancy test at screening, or women of childbearing potential not willing to use adequate contraception during the trial.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    GSK Clinical Trials
    Organizational Affiliation
    GlaxoSmithKline
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    24443277
    Citation
    Struemper H, Sale M, Patel BR, Ostergaard M, Osterborg A, Wierda WG, Hagenbeek A, Coiffier B, Jewell RC. Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis. J Clin Pharmacol. 2014 Jul;54(7):818-27. doi: 10.1002/jcph.268. Epub 2014 Jan 28.
    Results Reference
    derived
    PubMed Identifier
    20506254
    Citation
    Ostergaard M, Baslund B, Rigby W, Rojkovich B, Jorgensen C, Dawes PT, Wiell C, Wallace DJ, Tamer SC, Kastberg H, Petersen J, Sierakowski S. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum. 2010 Aug;62(8):2227-38. doi: 10.1002/art.27524.
    Results Reference
    derived

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    HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II

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