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

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants who previously participated in Study OFA112657 (NCT00291928) and who fulfilled the eligibility criteria were offered participation in this study (111752; NCT00655824).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A participant was considered to have completed the study when the Investigator decided that the participant had completed the treatment phase and recorded this in the Case Report Form. Completion was not based on having completed a set number of treatment courses.

Reporting Groups

Description

Ofatumumab 700 mg IV Infusion

Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.

Participant Flow:   Overall Study

	Ofatumumab 700 mg IV Infusion
STARTED	92
COMPLETED	8
NOT COMPLETED	84
Adverse Event	3
Early Termination of Study by Sponsor	74
Protocol Violation	1
Withdrawal by Subject	4
Deterioration of Trial Disease	2

1.  Primary:

Time to Treatment Withdrawal   [ Time Frame: From Baseline up to 144 weeks ]

2.  Secondary:

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. ]

3.  Secondary:

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. ]

4.  Secondary:

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. ]

5.  Secondary:

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 ]

6.  Secondary:

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. ]

7.  Secondary:

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. ]

8.  Secondary:

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. ]

9.  Secondary:

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. ]

10.  Secondary:

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. ]

11.  Secondary:

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. ]

12.  Secondary:

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. ]

13.  Secondary:

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. ]

14.  Secondary:

Whole Blood Transcriptional Profiles   [ 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. ]

15.  Secondary:

Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood   [ 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. ]

16.  Secondary:

CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3   [ 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. ]

17.  Secondary:

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. ]

18.  Secondary:

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. ]

19.  Secondary:

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. ]

20.  Secondary:

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. ]

21.  Secondary:

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. ]

22.  Secondary:

Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid   [ 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. ]

23.  Secondary:

Assessment of Total Protein (TP) and Albumin   [ 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. ]

24.  Secondary:

Assessment of Total Bilirubin (TB) and Creatinine   [ 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. ]

25.  Secondary:

Assessment of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT)   [ 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. ]

26.  Secondary:

Assessment of Blood Urea Nitrogen (BUN)   [ 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. ]

27.  Secondary:

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 ]

28.  Secondary:

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 ]

29.  Secondary:

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 ]

30.  Secondary:

Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK)   [ 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. ]

31.  Secondary:

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. ]