Last updated: 11/07/2018 03:49:50

Long-term efficacy and safety of repeated ofatumumab treatment courses in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403

GSK study ID
111752
See study documents
Clinicaltrials.gov ID
NCT00655824
See results summary
EudraCT ID
2007-004878-31
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: An open-label, international, multi-center, phase II, extension trial investigating long-term efficacy and safety of repeated treatment courses of ofatumumab, a fully human monoclonal anti-CD20 antibody, in adult patients with active rheumatoid arthritis who previously received ofatumumab or placebo
Trial description: A 3-year open-label trial for patients who previously participated in Trial Hx-CD20-403 and who fulfill the eligibility criteria for this trial (GEN413) . Th e primary purpose of the trial is to evaluate the long-term effectiveness of repeated courses ( a maximum of 9 treatment courses) of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:

Time to treatment withdrawal

Timeframe: From Baseline up to 144 weeks

Secondary outcomes:

Minimum change from Baseline in disease activity score based on 28 joints (DAS28) over the course of Weeks (Wk) 1 to 24 in each treatment course (TC), assessed by erythrocyte sedimentation rate (ESR; rate at which red blood cells sediment in 1 hour)

Timeframe: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Minimum change from Baseline in DAS28 over the course of Weeks 1 to 24 in each treatment course, based on C-reactive protein (CRP)

Timeframe: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Time to re-treatment in each treatment course

Timeframe: Week 16 to Week 104 of each treatment course (up to 125 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Ofatumumab serum concentration

Timeframe: Before infusion and at the end of infusion for each Treatment Course (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next TC; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial vi

Number of participants achieving American College of Rheumatology (ACR)20

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants achieving ACR50

Timeframe: Baseline of each TCand 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants achieving ACR70

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with the indicated European League Against Rheumatism (EULAR) response

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants in the indicated categories of the Health Assessment Questionnaire (HAQ)

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with the indicated Global Disease Assessment using the VAS

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with the indicated pain score

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with HAHA response

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Whole blood transcriptional profiles

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Percentage of cluster of differentiation (CD)19+, 4+, 3+, and 8+ B-cell subsets in the blood

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

CD19+, CD4+, CD3+, and CD8+ cell counts, measured in mm^3

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Ratio of CD 4+/CD8+

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with rheumatoid factor (RA factor) >13 International Units per milliliter

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with Anti-cyclic citrullinated peptide antibody (CCP) >6.9 International Units per liter

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with B-Lymphocyte Stimulator (BLyS) >2.49 micrograms per liter

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with Interleukin 6 (IL-6) >11.9 picograms per milliliter

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Assessment of sodium, potassium, chloride, bicarbonate, calcium, and uric acid

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Assessment of total protein (TP) and albumin

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Assessment of total bilirubin (TB) and creatinine

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Assessment of alanine aminotranferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), and gamma glutamyl-transferase (GGT)

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Assessment of blood urea nitrogen (BUN)

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Assessment of systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Timeframe: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk

Assessment of heart rate (HR)

Timeframe: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk

Assessment of body temperature (BT)

Timeframe: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk

Assessment of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK)

Timeframe: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Number of participants with normal and abnormal electrocardiogram readings

Timeframe: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Interventions:
  • Drug: ofatumumab
    • Enrollment:
    124
    Primary completion date:
    2011-25-05
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Emilia Quattrocchi, Mikkel Østergaard, Peter C. Taylor, Ronald F. van Vollenhoven, Myron Chu, Stephen Mallett, Hayley Perry, Regina Kurrasch. Safety of Repeated Open-label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials. PLoS ONE.2016
    Medical condition
    Arthritis, Rheumatoid
    Product
    ofatumumab
    Collaborators
    Not applicable
    Study date(s)
    January 2008 to March 2013
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Previously received ofatumumab or placebo in Trial Hx-CD20-403.
    • Patients on methotrexate therapy (7.5 – 25 mg/week, p.o., i.m., and/or s.c.).
    • Use of DMARDs other than methotrexate or exposure to other cell depleting therapy, including investigational compounds < 6 months prior to Visit 2 A.
    • Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening).
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Previously received ofatumumab or placebo in Trial Hx-CD20-403. -Patients on methotrexate therapy (7.5 – 25 mg/week, p.o., i.m., and/or s.c.). -Oral corticosteroids therapy (≤ 10 mg/day prednisolone or equivalent). -Active disease at the time of screening as defined by: ≥ 3 swollen joints (of 28 joints assessed) and ≥ 3 tender joints (of 28 joints assessed), DAS28≥3.2 (based on ESR)
    Exclusion criteria:
    • Use of DMARDs other than methotrexate or exposure to other cell depleting therapy, including investigational compounds < 6 months prior to Visit 2 A. -Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening). -Breast feeding women or women with a positive pregnancy test at Visit 1 (screening). -Received anti-cancer therapy, corticosteroids (intra-articular, i.m., or i.v.), or live/attenuated vaccinations, or exposure to cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents < 5 years prior to screening. -Past or current malignancy, except for 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 ongoing active infectious disease requiring systemic treatment. -Clinically significant cardiac disease, or history of significant cerebrovascular disease. Significant concurrent, uncontrolled medical conditions, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease -Known or suspected HIV positive, positive serology for hepatitis B (HB), positive test for Hepatitis C, or positive plasma or white cell JC virus (JCV) PCR (either compartment). -A circulating IgG level

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    New York, New York, United States, 10003
    Status
    Terminated/Withdrawn
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    Location
    GSK Investigational Site
    Los Angeles, California, United States, 90095
    Status
    Terminated/Withdrawn
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    Location
    GSK Investigational Site
    Szombathely, Hungary, 9700
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Glostrup, Denmark, 2600
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Ipswich, United Kingdom, IP4 5PD
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Warszawa, Poland, 02-256
    Status
    Will Be Recruiting
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    Showing 1 - 6 of 10 Results

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2011-25-05
    Actual study completion date
    2013-19-03

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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