Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403

This study has been terminated.
(The clinical development of intravenously administered ofatumumab in RA will no longer be pursued, so this study was prematurely terminated by the Sponsor.)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00655824
First received: April 4, 2008
Last updated: September 19, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: ofatumumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Time to Treatment Withdrawal [ Time Frame: From Baseline up to 144 weeks ] [ Designated as safety issue: No ]
    Time to treatment withdrawal was defined as the time from the first infusion of ofatumumab until the date of treatment withdrawal. The sponsor discontinued the intravenous route of administration development program for rheumatoid arthritis (RA), and this study was terminated early; hence, this primary endpoint was not evaluated.


Secondary Outcome Measures:
  • 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) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    DAS28(ESR) is a numeric outcome that measures RA activity based on the ESR (a non-specific general indicator of inflammation), tender joint count (JC), swollen JC, and participant's global assessment of disease activity on a 100 millimeter Visual Analog Scale. DAS28 values range from 0 (no activity) and upwards; increasing values indicate increasing activity (there is no upper limit on the scale). Change from baseline (CFB) was calculated at all visits; however, minimum CFB was calculated as the minimum CFB obtained over the course of weeks 1-24 of each treatment cycle.

  • Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    DAS28(CRP) is a numeric outcome that measures RA activity based on the CRP (used to monitor acute inflammatory phases of RA), tender JC, swollen JC, and participant's global assessment of disease activity on a 100 millimeter Visual Analog Scale. DAS28 values range from 0 (no activity) and upwards; increasing values indicate increasing activity (there is no upper limit on the scale). Change from baseline (CFB) was calculated at all visits; however, minimum CFB was calculated as the minimum CFB obtained over the course of weeks 1-24 of each treatment cycle.

  • Time to Re-treatment in Each Treatment Course [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Time to re-treatment in each treatment course (TC) is defined as the time from the first infusion of ofatumumab until the date of the first infusion of the first re-treatment course. The data presented reflect the time to re-treatment, which is defined as the time in days between the first infusion of each TC and the first infusion of the following TC. For TC 1, time to re-treatment is defined as the time between the first infusion in TC 1 and the first infusion in TC 2; similarly, for TC 2 it is the time between the first infusion of TC 2 and the first infusion of TC 3.

  • Ofatumumab Serum Concentration [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the measurement of ofatumumab concentration in the blood. The blood samples were collected before infusion (BI) (baseline of that particular treatment course) and at the end of infusion (EI) of ofatumumab.

  • Number of Participants Achieving American College of Rheumatology (ACR)20 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    ACR20 is achieved if the participant has 20% improvement from Baseline in TJC and SJC and in 3 out of 5 of following assessments (A); participant pain A, participant global A, physician global A on a visual analog scale (VAS: a 10 cm scale ranging from "no pain" to "severe pain"; the distance marked by the participant from the "no pain" end is his joint pain score), participant self-assessed disability, and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants Achieving ACR50 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    ACR50 is achieved if the participant has 50% improvement from Baseline in: TJC and SJC and in 3 out of 5 of following assessment (A) ; participant pain A , participant global A, physician global A on a visual analogue scale (VAS: a 10 cm scale ranges from 'no pain' to 'severe pain' and the distance marked by the participant from the "no pain" end is his joint pain score).and participant self-assessed disability and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants Achieving ACR70 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    ACR70 is achieved if the participant has 70% improvement from Baseline in: TJC and SJC and in 3 out of 5 of following assessment (A) ; participant pain A , participant global A, physician global A on a visual analogue scale (VAS: a 10 cm scale ranges from 'no pain' to 'severe pain' and the distance marked by the participant from the "no pain" end is his joint pain score).and participant self-assessed disability and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response [ Time Frame: 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. ] [ Designated as safety issue: No ]
    EULAR response is based on the DAS score. EULAR response criterion classifies participants as good or moderate responders and non-responders. Good response: DAS28 score <=3.2 and >1.2 improvement from Baseline (IfB) in DAS28 score, Moderate response: DAS28 score <=3.2 and between >0.6 and <=1.2 IfB; DAS28 score between >3.2 and <=5.1 and >1.2 IfB; DAS28 score between >3.2 and <=5.1 and between >0.6 and <=1.2 IfB; DAS28 score >5.1 and >1.2 IfB. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants in the Indicated Categories of the Health Assessment Questionnaire (HAQ) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The HAQ, a 20-question instrument, assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each area are scored from 0 (no difficulty) to 3 (inability to perform a task in that area). The index is calculated by adding all scores, then dividing this score by the total number of components answered. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants With the Indicated Global Disease Assessment Using the VAS [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The participant and the physician independently used the VAS for overall assessment of the disease. VAS is used to measure the physician's subjective assessment of the participant's RA disease process at the time of the visit. The scale ranged from 0 (extremely well) to 10 (extremely poor). The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants With the Indicated Pain Score [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The pain score was assessed using the VAS: a 10 cm scale ranging from "no pain" to "severe pain"; the distance marked by the participant from the "no pain" end is his joint pain score. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Number of Participants With HAHA Response [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The host immune response was assessed based on Human Anti-Human Antibodies (HAHA). The serum samples of the participants were collected for the assessment of HAHA. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Whole Blood Transcriptional Profiles [ Time Frame: Baseline (BL) of each TC and 8 wk post infusion (PI), 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. ] [ Designated as safety issue: No ]
    Blood samples were collected for transcriptomic analysis of messenger ribonucleic acid (mRNA). The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

  • Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of CD19+, CD4+, CD3+, and CD8+ B-cell subsets. These biomarkers are associated with immune functions. Only CD19+ cells were measured in the Follow-up Period.

  • CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3 [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of CD19+, CD4+, CD3+, and CD8+ cell counts. These cells are present on white blood cells and are used as markers to associate cells with immune functions. Only CD19+ cells were measured in the Follow-up Period.

  • Ratio of CD 4+/CD8+ [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of CD4+ and CD8+ cell counts and the ratio was calculated.

  • Number of Participants With Rheumatoid Factor (RA Factor) >13 International Units Per Milliliter [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of RA factor. RA factor is an antibody found in the blood of participants with rheumatoid arthritis and is used for the diagnosis of rheumatoid arthritis.

  • Number of Participants With Anti-cyclic Citrullinated Peptide Antibody (CCP) >6.9 International Units Per Liter [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of Anti-CCP. Anti-CCP plays an important role in immune response and helps assess the disease condition.

  • Number of Participants With B-Lymphocyte Stimulator (BLyS) >2.49 Micrograms Per Liter [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of BLyS. BLyS is a potent co-stimulator of B lymphocytes, and elevated levels of BLyS are observed in autoimmune diseases. It regulates the immunoglobin (antibody produced by B cells that is used by the immune system to identify bacteria and viruses in the body) secretion of normal B cells (type of cells in the blood).

  • Number of Participants With Interleukin 6 (IL-6) >11.9 Picograms Per Milliliter [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of IL-6. IL-6 plays an important role in immune response and helps assess the disease condition.

  • Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of uric acid and electrolytes (sodium, potassium, chloride, and calcium), as increased levels may reflect B-cell lysis due to treatment with ofatumumab.

  • Assessment of Total Protein (TP) and Albumin [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected to evaluate TP and albumin. TP can vary depending on auto-immune diseases, and TP and albumin can vary depending on debilitating diseases.

  • Assessment of Total Bilirubin (TB) and Creatinine [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected to evaluate TB and creatinine levels. TB evaluation is performed to assess the condition of the liver, and possible hemolytic anemia, and the creatinine evaluation is performed to assess the renal condition (condition of the kidneys).

  • Assessment of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT) [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of ALT, AST, AP, and GGT. AST, ALT, AP, and GGT are evaluated to assess the condition of the liver.

  • Assessment of Blood Urea Nitrogen (BUN) [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    The blood samples of participants were collected to assess the amount of nitrogen (in the form of urea) in the blood. BUN is evaluated to assess the renal function of the participants.

  • Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The blood pressure (BP) of the participants was measured before infusion (infu) (BI) and post the first (A) and second (B) infusions (PI) during all 7 treatment courses. Timing for taking BP readings: SBP (BP when the heart is contracting): TC1, 2, 3 (infu A) more than 2 hours PI; TC1, 2 ,3 (infu B) 2 hours PI; TC4, 5, 6, 7 (infu A) 2 hours PI; TC4, 7 (infu B) 2 hours PI; TC5, 6 (infu B) 1 hour PI. For DBP (BP when the heart is resting between beats): TC1, 3 (infu A) more than 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC1, 2, 3, 4, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.

  • Assessment of Heart Rate (HR) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The HR of the participants was measured to assess the condition of the heart. HR was measured BI and post the first (A) and second (B) infusions during all 7 treatment courses. Timing for measuring HR: TC1, 3 (infu A) more than 2 hours PI; TC1, 2 ,3, 4, 7 (infu B) 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.

  • Assessment of Body Temperature (BT) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The BT of the participants was measured BI and post the first (A) and second (B) infusions (PI) of each cycle to assess the effect of ofatumumab on the BT. The BT of the participants was measured before BI and PI A and B during all 7 treatment courses. Timing for taking BT reading: TC1, 3 (infu A) more than 2 hours PI; TC1, 2 ,3, 4, 7 (infu B) 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.

  • Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected to assess LDH and CPK. Both tests are performed to evaluate the injury and damage to the body tissue, potentially from B-cell lysis.

  • Number of Participants With Normal and Abnormal Electrocardiogram Readings [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Electrocardiograms of the participants were taken. The abnormal clinically significant (CS) and not clinically significant (NCS) reading, as determined by the Investigator, were recorded.

  • Number of Participants With Grade 3 and 4 Neutropenia Events (NEs) [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of absolute neutrophil count. A Grade 3 NE was defined as absolute neutrophil count below the following values: absolute neutrophil count <1000-500/mm^3; <1.0-0.5 x 10^9/L. A Grade 4 NE was defined as absolute neutrophil count below the following values: absolute neutrophil count <500/mm3; <0.5 x 10^9/L. Blood samples of participants were collected for the evaluation of platelet count. Grade 3 thrombocytopenia was defined as platelet counts below the following values: platelet count <50000-25000/mm^3; <50.0-25.0 x 10^9/L. Grade 4 thrombocytopenia was defined as platelet counts below the following values: platelet count <25000/mm^3; <25.0 x 10^9/L.

  • Number of Participants With Repopulated CD19+ Cell Counts at the Indicated Time Points [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of the CD19+ B-cell subset. The number of participants with repopulated CD19+ cell counts was determined. A participant was defined as repopulated at a visit if the cell count was >=the lower limit of normal (LLN) or the Baseline value, whichever was lower. Baseline was defined as the Baseline value from Study OFA112657.

  • Time to CD19+ Repopulation Relative to Baseline [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of the CD19+ B-cell subset. A participant was defined as repopulated at a visit if the CD19+ cell count was >=the lower limit of normal (LLN) or the Baseline value, whichever was lower. Time to the first repopulation relative to Baseline was calculated as: (the date of the first sample where CD19+ was greater than or equal to the minimum of the LLN and the Baseline value minus the Baseline date + 1) divided by 365.25. Baseline was defined as the Baseline value from Study OFA112657.

  • Time to CD19+ Cell Repopulation From the Time of the Last Ofatumumab Dose [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the evaluation of the CD19+ B-cell subset. A participant was defined as repopulated at a visit if the CD19+ cell count was >=the lower limit of normal (LLN) or the Baseline value, whichever was lower. Time to the first repopulation relative to the last ofatumumab treatment was calculated as: (the date of the first sample where CD19+ was greater than or equal to the minimum of the LLN and the Baseline value minus the date of last dose of ofatumumab + 1) divided by 30.4375. Baseline was defined as the Baseline value from Study OFA112657.

  • Number of Participants With Postive or Negative Plasma/White Cell John Cunningham Virus (JCV) Polymerase Chain Reaction (PCR) Test Results [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples were collected, and the plasma/white cell JCV PCR test was performed for qualitative analysis of plasma/white cell JCV DeoxyriboNucleic Acid (DNA). Participants with positive results on at least one visit (any visit) are included in the indicated positive category. Positive test results denoted presence of the indicated parameters and Negative test results denoted absence of the indicated parameters.

  • Number of Participants With Postive or Negative Results of Testing for Anti-HBc, Anti-HBs, and HBsAG [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 24 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples were collected, and participants were evaluated for serologic evidence of Hepatitis B (HB) infection based on the results of testing for HBsAg, anti-HBc, and anti-HBs antibodies. Participants with positive results on at least one visit (any visit) are included in the indicated positive category. Positive test results denoted presence of the indicated parameters and Negative test results denoted absence of the indicated parameters.

  • Number of Participants With Any Signs/Symptoms of Progressive Multifocal Leukoencephalopathy (PML) [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    A neurological examination to detect any signs or symptoms consistent with a diagnosis of PML was conducted. Signs and symptoms of PML includ visual disturbances, ocular movements, ataxia, and changes in mental status such as disorientation or confusion. Participants with any signs/symptoms of PML on at least one visit (any visit) are included in the "Yes" category.

  • Number of Participants With a Positive or Negative Pregnancy Test Results. [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then Weeks 12 and 24 of follow-up (up to Study Wk 156). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Serum and urine pregnancy testing were performed for women of childbearing potential.

  • Number of Participants With Immunoglobulin A (IgA) <0.7 Grams Per Liter (g/L) or >4 g/L, Immunoglobulin M (IgM) <0.5 g/L or >3 g/L, and Immunoglobulin G (IgG) <6.5 g/L or >16 g/L at the Indicated Time Points [ Time Frame: BL of each TC and 8 wk PI, then every 4 wk until Wk 24, then every 8 wk until next TC, then every 12 wk follow-up (up to Study Wk 204). TCs were individualized based on clinical status and may not correlate to trial visits or study wk ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the measurement of IgA, IgG, and IgM.


Enrollment: 124
Study Start Date: January 2008
Study Completion Date: March 2013
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab
1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl
Drug: ofatumumab
1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl

Detailed Description:

All patients who fulfill the eligibility criteria for this trial , will initiate at least one treatment course of ofatumumab, and depending of subsequent worsening in disease activity will be eligible to received further treatment through the 156 week treatment period: a maximum of a further 8 treatment courses will be given at individualized time intervals . The interval between each treatment course will be at least 16 weeks with the last treatment course given no later than week 130 after baseline (Visit 2A).

After each treatment course the patients will attend their next trial visit 8 weeks after Infusion 1, followed by trial visits every 4 weeks up to Week 24, and subsequently every 8 weeks until the next treatment course.

After completing the Treatment Period or after withdrawing from the Treatment Period prematurely patients will be followed every 12 weeks (Follow-up Period) until CD19+ cells &/or IgG levels have returned to baseline or normal levels.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 <lower limit of normal.
  • Known hypersensitivity to components of the investigational medicinal product.
  • Patients known or suspected of not being able to comply with a study protocol.
  • Women of child bearing potential not will to use adequate contraception during study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00655824

Locations
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90095
United States, Florida
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33334
United States, New York
GSK Investigational Site
New York, New York, United States, 10003
United States, Pennsylvania
GSK Investigational Site
Duncansville, Pennsylvania, United States, 16635
Denmark
GSK Investigational Site
Glostrup, Denmark, 2600
GSK Investigational Site
Hellerup, Denmark, 2900
GSK Investigational Site
Koebenhavn, Denmark, 2100
Hungary
GSK Investigational Site
Szombathely, Hungary, 9700
Poland
GSK Investigational Site
Warszawa, Poland, 02-256
United Kingdom
GSK Investigational Site
Ipswich, United Kingdom, IP4 5PD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00655824     History of Changes
Other Study ID Numbers: 111752, GEN413
Study First Received: April 4, 2008
Results First Received: March 26, 2012
Last Updated: September 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014