This is a phase III, double-blind, randomized, multicenter, and parallel group trial with a duration of 24 weeks, followed by a 120 week Open-label Period. The primary purpose of the study is to demonstrate the efficacy and safety of ofatumumab in reducing clinical signs and symptoms in adult RA patients who had an inadequate response to TNF-α antagonist therapy.
This study consist of a double-blind, placebo controlled, and parallel group part with eligible patients enrolled into a 24 week Double-Blind Period, and randomized in a 1:1 ratio to receive either ofatumumab or placebo in addition to their background methotrexate treatment. Patients who complete the 24 week Double-blind Period without receiving rescue DMARD treatment will then be eligible to proceed into the 120 week Open-label Period to receive repeat treatment courses with ofatumumab. In the Open-label Period ofatumumab treatment courses will be given at individualized time intervals only if a clinical response has been achieved following the previous treatment course, and followed by a subsequent worsening in disease activity. Patients who have completed the Open-label Period or have been withdrawn will then enter a maximum 2 year Follow-up Period, or until there B-cells return to normal or to baseline levels, whichever occurs earlier
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
169
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each treatment cycle consisting of two IV infusion taken 14 days apart. A total of 8 infusion cycles given over a 144 week period
1000 mL sterile, pyrogen free 0.9% NaCl. A treatment cycle consisting of two IV infusion taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period
Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24
The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR20 if he experienced \>=20% improvement from baseline in TJC and SJC and a \>=20% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
Time frame: Baseline and Week 24
Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Weeks 4, 8, 12, 16, and 20
The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR20 if he experienced \>=20% improvement from baseline in TJC and SJC and a \>=20% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
Time frame: Baseline and Weeks 4, 8, 12, 16, and 20
Number of Participants With a 50% Improvement From Baseline in Their ACR Score (ACR50) at Weeks 4, 8, 12, 16, 20, and 24
The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR50 if he experienced \>=50% improvement from baseline in TJC and SJC and a \>=50% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
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GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
GSK Investigational Site
Rosario, Santa Fe Province, Argentina
GSK Investigational Site
Córdoba, Argentina
GSK Investigational Site
San Miguel de Tucumán, Argentina
GSK Investigational Site
Herlev, Denmark
GSK Investigational Site
Silkeborg, Denmark
GSK Investigational Site
Amiens, Picardie, France
GSK Investigational Site
Cahors, France
GSK Investigational Site
Corbeil-Essonnes, France
GSK Investigational Site
Échirolles, France
...and 50 more locations
Number of Participants With a 70% Improvement From Baseline in Their ACR Score (ACR70) at Weeks 4, 8, 12, 16, 20, and 24
The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR70 if he experienced \>=70% improvement from baseline in TJC and SJC and a \>=70% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Mean Disease Activity Score Based on 28 Joints (DAS28) at Weeks 4, 8, 12, 16, 20, and 24 Using C-reactive Protein (CRP) as the Acute Phase Reactant (APR)
The DAS28 is a clinical index of rheumatoid arthritis disease activity (DA) that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of DA can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. APRs are a class of proteins that are useful markers for inflammation.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant
The DAS28 is a clinical index of rheumatoid arthritis disease activity (DA) that combines information from swollen and tender joints, the APR, and general health (patient global assessment). The level of DA can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. APRs are a class of proteins that are useful markers for inflammation. Change from baseline in DAS28 is calculated as the Week 4, 8, 12, 16, 20, and 24 values minus the baseline value.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using Erythrocyte Sedimentation Rate (ESR) as the Acute Phase Reactant (ARP)
The DAS28 is a clinical index of rheumatoid arthritis disease activity (DA) that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of DA can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. APRs are a class of proteins that are useful markers for inflammation.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant
The DAS28 is a clinical index of rheumatoid arthritis disease activity (DA) that combines information from swollen and tender joints, the APR, and general health (patient global assessment). The level of DA can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. APRs are a class of proteins that are useful markers for inflammation. Change from baseline in DAS28 is calculated as the Week 4, 8, 12, 16, 20, and 24 values minus the baseline value.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 \<=3.2; moderate responders: change from baseline \>1.2 with DAS28 \<=3.2 to \>5.1 or change from baseline \>0.6 to \<=1.2 with DAS28 \<=3.2 to \<=5.1); non-responders: change from baseline \<=0.6 or change from baseline \>0.6 and \<=1.2 with DAS28 \>5.1.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 \<=3.2; moderate responders: change from baseline \>1.2 with DAS28 \<=3.2 to \>5.1 or change from baseline \>0.6 to \<=1.2 with DAS28 \<=3.2 to \<=5.1); non-responders: change from baseline \<=0.6 or change from baseline \>0.6 and \<=1.2 with DAS28 \>5.1.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Median of the Largest Integer n, for Which a Participant Met the ACR Criteria Requiring an Improvement of n% (ACRn) at Weeks 4, 8, 12, 16, 20, and 24
ACRn = the largest integer n for which a participant (par.) met the criteria requiring an improvement of n%. ACRn is a measure characterizing percentage (%) improvement from baseline (IFBL). A par. with an ACRn of X had an improvement of \>=X% in tender/swollen joints (TJC/SJC), and an improvement of \>=X% in 3 of the 5 parameters (patient \[pt\] pain assessment, pt global assessment \[GA\], physician GA, pt self-assessed disability, acute phase reactant). ACRn = min(TJC % IFBL, SJC % IFBL, composite measure % IFBL). Composite measure % IFBL is the 3rd highest value of % IFBL for the 5 parameters.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 4, 8, 12, 16, 20, and 24
The HAQ-DI is a 20-question instrument used to assess the degree of difficulty a participant had in accomplishing tasks in 8 functional areas (FAs): dressing, arising, eating, walking, hygiene, reaching, gripping, and errands/chores. Responses for each FA were scored from 0 (no difficulty) to 3 (inability to perform a task). The total score (range of 0-3) was calculated by adding the 8 individual FA scores, then dividing this sum by the total number of components answered. Responders were defined as participants achieving an improvement from baseline in the HAQ-DI score at Week 24 of \>=0.22.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Change From Baseline in Tender Joint Count at Week 24
Change from baseline in tender joint count was calculated as the Week 24 count minus the baseline count. A total of 68 joints were assessed. Joints were classified as either tender or not tender by an independent assessor, who had documented experience in performing joint assessments.
Time frame: Baseline and Week 24
Change From Baseline in Swollen Joint Count at Week 24
Change from baseline in swollen joint count was calculated as the Week 24 count minus the baseline count. A total of 66 joints were assessed. Joints were classified as either swollen or not swollen by an independent assessor, who had documented experience in performing joint assessments.
Time frame: Baseline and Week 24
Change From Baseline in CRP at Week 24
Blood samples for the determination of CRP were taken at pre-specified visits and were sent to the central laboratory for analysis. Change from baseline in CRP was calculated as the Week 24 value minus the baseline value. CRP is an acute-phase protein whose plasma concentration increases in response to inflammation. CRP is a useful marker of inflammation.
Time frame: Baseline and Week 24
Change From Baseline in ESR at Week 24
ESR is measured by a blood test that shows the rate at which red blood cells sediment in a period of 1 hour. Blood samples for the determination of ESR were taken at pre-specified visits and were measured immediately at the trial site. Change from baseline in ESR was calculated as the Week 24 value minus the baseline value.
Time frame: Baseline and Week 24
Change From Baseline in the Participant-assessed Pain Score Using Visual Analogue Scale (VAS) at Week 24
A horizontal VAS of 100 mm was used to report the participant's level of joint pain. The scale ranged from 0 (no pain) to 100 (unbearable pain). Participants were instructed to draw a vertical line through the horizontal line to indicate how much joint pain they had. The distance from the "no pain" end to the vertical line drawn by the participant was the joint pain score. Change from baseline was calculated as the Week 24 value minus the baseline value.
Time frame: Baseline and Week 24
Change From Baseline in Participant-assessed Global Disease Score Using VAS at Week 24
The participant used a horizontal VAS of 100 mm for overall assessment of disease. The scale ranged from 0 (very well) to 100 (very poor). Participants were instructed to draw a vertical line through the horizontal line to indicate the state of the arthritis. The distance from the "very well" end to the vertical line drawn by the participant was the global disease assessment score. Change from baseline in participant-assessed global disease was calculated as the Week 24 value minus the baseline value.
Time frame: Baseline and Week 24
Change From Baseline in the Physician-assessed Global Disease Score Using VAS at Week 24
The physician used a horizontal VAS of 100 mm for overall assessment of disease. The scale ranged from 0 (very well) to 100 (very poor). Physicians were instructed to draw a vertical line through the horizontal line to indicate the state of the arthritis. The distance from the "very well" end to the vertical line drawn by the participant was the global disease assessment score. Change from baseline in the physician-assessed global disease was calculated as the Week 24 value minus the baseline value.
Time frame: Baseline and Week 24
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Questionnaire Score at Week 24
The FACIT-F score has a valid range of values from 0 to 52, with a higher score indicating a lower burden of fatigue. The subset determining fatigue contains 13 questions. Responses to each question were scored from 0, indicating "Not at all fatigued," to 4, indicating "Very much fatigued."
Time frame: Baseline and Week 24
Change From Baseline in the Short-Form 36 (SF-36v2) Norm-based Scores for Physical Component Summary and Physical Items at Week 24
The SF-36v2 is a standardized questionnaire used to measure overall subjective health status by measuring 8 health-related parameters (each scored from 0 \[poorer health\] to 100 \[better health\]): body pain, general mental health (MH), perception of general health, physical functioning, role limitations (RL) caused by mental condition, RL caused by a physical condition, social functioning, and vitality. It yields an 8-scale profile of functional health and well-being scores, as well as psychometrically based physical and MH summary measures and a preference-based health utility index.
Time frame: Baseline and Week 24
Change From Baseline in the SF-36v2 Norm-based Scores for Mental Component Summary and Mental Items at Week 24
The SF-36v2 is a standardized questionnaire used to measure overall subjective health status by measuring 8 health-related parameters (each scored from 0 \[poorer health\] to 100 \[better health\]): body pain, general mental health (MH), perception of general health, physical functioning, role limitations (RL) caused by mental condition, RL caused by a physical condition, social functioning, and vitality. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and MH summary measures and a preference-based health utility index.
Time frame: Baseline and Week 24
Biomarker Levels for Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at Baseline and Week 4
The following biomarkers were assessed: Anti-Cyclic Citrullinated Peptide 3 antibody (Anti-CCP), Rheumatoid factor IgA (RF-IgA), RF IgG (RF-IgG), and RF IgM (RF-IgM). Measurements of RF were used to characterize participants' disease activity and immune status. Anti-CCP was used to characterize the disease type and the immune status of the participants. Assessments for which results were below the lower limit of quantification (LLQ) were reported using a value of LLQ/2. Assessments for which results were above the upper limit of quantification (ULQ) were reported using a value of ULQ.
Time frame: Baseline and Week 4
Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Week 24
Detection of human anti-human antibodies (HAHAs) against ofatumumab was to be performed by Electrochemiluminescent (ECL) Meso-Scale Discovery (MSD) immunoassay. Positive samples from the binding antibody test were also tested in a neutralizing antibody assay.
Time frame: Baseline and Week 24
Change From Baseline in Levels of IgA, IgG and IgM at Week 12 and Week 24
The following immunoglobulins were assessed: IgA, IgG and IgM. Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression.
Time frame: Baseline, Week 12, and Week 24
Minimum DAS28-ESR Score During the DB and OL Periods, by Ofatumumab Treatment Course
The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. The values summarized are the minimum DAS28 score (i.e. lowest level of disease activity) achieved by each participant within the first 24 weeks of each treatment course (TC), assessed using erythrocyte sedimentation rate (ESR; rate at which red blood cells sediment in 1 hour).
Time frame: First 24 weeks of each treatment course (assessed up to Week 144)
Minimum DAS28-CRP Score During the DB and OL Periods, by Ofatumumab Treatment Course
The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. The values summarized are the minimum DAS28 score (i.e. lowest level of disease activity) achieved by each participant within the first 24 weeks of each treatment course, assessed using C-reactive Protein (CRP: used to monitor acute inflammatory phases of rheumatoid arthritis).
Time frame: First 24 weeks of each treatment course (assessed up to Week 144)
Minimum Change From Baseline DAS28-ESR Score, During the DB and OL Periods, by Ofatumumab Treatment Course
The level of rheumatoid arthritis disease activity based on the DAS28 score is defined as low if DAS28 \<=3.2, moderate if 3.2\< DAS28 \<=5.1, or high if DAS28 \> 5.1. A DAS28 \<2.6 corresponds to clinical remission. The values summarized are the minimum change from baseline DAS28 score (i.e. greatest change in disease activity during the treatment course) achieved by each participant within the first 24 weeks of each treatment course, assessed by using ESR. Baseline score was determined at the start of each treatment course. For change from baseline, participants had to have both a baseline DAS28 value for the treatment course (i.e., the latest value on or before the date of infusion A of the treatment course, providing it was done within a 14 day window prior to the date of infusion A) and a DAS28 value during the treatment course (i.e., during first 24 weeks of each treatment course). Change from baseline was calculated as the value during the treatment course minus the baseline value.
Time frame: First 24 weeks of each treatment course (assessed up to Week 144)
Minimum Change From Baseline DAS28-CRP Score, During the DB and OL Periods, by Ofatumumab Treatment Course
The level of rheumatoid arthritis disease activity based on the DAS28 score is defined as low if DAS28 \<=3.2, moderate if 3.2\< DAS28 \<=5.1, or high if DAS28 \> 5.1. A DAS28 \<2.6 corresponds to clinical remission. The values summarized are the minimum change from baseline DAS28 score (i.e. greatest change in disease activity during the treatment course) achieved by each participant within the first 24 weeks of each treatment course, assessed by using CRP. Baseline score was determined at the start of each treatment course. For change from baseline, participants had to have both a baseline DAS28 value for the treatment course (i.e., the latest value on or before the date of infusion A of the treatment course, providing it was done within a 14 day window prior to the date of infusion A) and a DAS28 value during the treatment course (i.e., during first 24 weeks of each treatment course). Change from baseline was calculated as the value during the treatment course minus the baseline value.
Time frame: First 24 weeks of each treatment course (assessed up to Week 144)
Time to Retreatment, by Ofatumumab Treatment Course
Time to retreatment is defined as the time in days between infusion A of each treatment course and infusion A of the following treatment course. For participants randomized to ofatumumab in the Double-blind Period, Treatment Course 1 refers to the course of ofatumumab received in the Double-blind Period. The minimum period allowed per protocol before retreatment was 24 weeks (end of Double-blind Period). For participants randomized to placebo in the Double-blind Period, Treatment Course 1 refers to the first course of ofatumumab received in the Open-label Period. The minimum period allowed per protocol before retreatment during the Open-label Period was 16 weeks.
Time frame: From Baseline up to Week 144
Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using ESR), During the DB and OL Periods, by Ofatumumab Treatment Course
The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. Remission is defined as a DAS28 score \<2.6 at any time during the first 24 weeks of each treatment course. Low disease activity is defined as a DAS28 score \>=2.6 and \<3.2 at any time during the first 24 weeks of each treatment course.
Time frame: First 24 weeks of each treatment course (assessed up to Week 144)
Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using CRP), During the DB and OL Periods, by Ofatumumab Treatment Course
The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28\<=3.2), moderate (3.2\<DAS28\<=5.1), or high (DAS28\>5.1); total score, 0-9.4. A DAS28 \<2.6 corresponds to remission. Remission is defined as a DAS28 score \<2.6 at any time during the first 24 weeks of each treatment course. Low disease activity is defined as a DAS28 score \>=2.6 and \<3.2 at any time during the first 24 weeks of each treatment course.
Time frame: First 24 weeks of each treatment course (assessed up to Week 144)
Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event, During the DB and OL Periods, by Ofatumumab Treatment Course
An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold \>=2%) and SAEs.
Time frame: First treatment (Day 0) until the participant terminated the trial, assessed up to Week 144
Number of Participants With the Indicated Electrocardiogram (ECG) Findings, During the OL Period
The number of participants with normal, abnormal clinically significant (CS), and abnormal not clinically significant (NCS) ECG findings, as well as the number of participants with no results (NR), during the OL Period are presented. An overall interpretation of the ECG was made by the investigator, or the investigator could delegate this task to a cardiologist, if applicable.
Time frame: From DB Period completion (Week 24) until the completion of the OL Period, assessed up to Week 144
Number of Participants With a CD19+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at Indicated the Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course
The number of participants with a CD19+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 giga \[10\^9\] per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Time frame: From baseline up to Week 144
Number of Participants With a CD3+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course
The number of participants with a CD3+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 gill per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Time frame: From baseline up to Week 144
Number of Participants With a CD4+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point , During the DB and OL Periods, by Ofatumumab Treatment Course
The number of participants with a CD4+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 gill per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Time frame: From baseline up to Week 144
Number of Participants With a CD8+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point , During the DB and OL Periods, by Ofatumumab Treatment Course
The number of participants with a CD8+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 gill per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Time frame: From baseline up to Week 144
Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. The baseline (BL) value for a treatment course is defined as the latest value on or before the date of infusion A of the treatment course. The post-baseline (PBL) visit is defined as any visit after the date of infusion A during the specified treatment course. Pre-defined limits of potential clinical concern (CC Low \[relative to the lower limit of normal\], CC High \[relative to the upper limit of normal\]) are: Albumin: 0.9, 1.5; Alanine amino transferase (ALT): NA, 2; Alkaline phosphatase (ALP): NA, 1.5; Aspartate amino transferase (AST): NA, 2; Bilirubin total (TBIL): NA, 1.5; Calcium: 0.85, 1.08; CO2 content/bicarbonate (BCO): 0.85, 1.2; Creatine kinase (CK): NA, 2; Creatinine: NA, 1.2; Gamma glutamyl transferase (GGT): NA, 2; Potassium: 0.9, 1.1; Urea/blood urea nitrogen (BUN): NA, 1.5; Uric acid: NA, 1.5.
Time frame: From baseline up to Week 144
Number of Participants With the Indicated Hematology Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. The baseline (BL) value for a treatment course is defined as the latest value on or before the date of infusion A of the treatment course. The post-baseline (PBL) visit is defined as any visit after the date of infusion A during the specified treatment course. Pre-defined limits of potential clinical concern (CC Low \[relative to lower limit of normal\], CC High \[relative to upper limit of normal\]) are: Eosinophils: NA, 2; Hematocrit (HCT): 0.75, 1.2; Hemoglobin (Hb): 0.75, 1.2; Monocytes: 0.2, 5 2; Neutrophils total (TNUE): 0.8, 1.6; Platelet count (PC): 0.65, 1.5; Red blood cell count (RBC): 0.7, 5 2; White blood cell count (WBC): 0.7, 1.6.
Time frame: From baseline up to Week 144
Number of Participants With Vital Sign Data Outside the Clinical Concern Range at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
The baseline value for a treatment course is defined as the value before infusion A of each treatment course. The post-baseline visit is defined as any assessment during or after the start of infusion A during the specified treatment course. Pre-defined limits of potential clinical concern for vital signs (Low, High) are: Diastolic blood pressure (DBP) (millimeters of mercury \[mmHg\]): 40, 110; Systolic blood pressure (SBP) (mmHg): 90, 170; Heart rate (beats per minute): 35, 120. LLN=lower limit of normal; ULN=upper limit of normal.
Time frame: From baseline up to Week 144
Number of Participants With Immunoglobulin Values Outside the Reference Range at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
The baseline value for a treatment course is defined as the latest value on or before the date of infusion A of the treatment course. The post-baseline visit is defined as any visit after the date of infusion A during the specified treatment course. Reference ranges (LLN, ULN) used for immunoglobulins are: immunoglobulin A (IgA) (grams/Liter): 0.81, 4.63; immunoglobulin G (IgG) (grams/Liter): 6.94, 16.18; immunoglobulin M (IgM) (grams/Liter): 0.48, 2.71.
Time frame: From baseline up to Week 144
Number of Participants With Positive John Cunningham (JC) Virus Test Results at Baseline or Any Visit Post-baseline During the DB and OL Periods
Blood samples were collected for analysis of plasma/white blood cell JC Virus (JCV) using the polymerase chain reaction (PCR) assay. A positive JC Virus test result indicates the presence of JC Virus.
Time frame: From basline up to Week 144
Number of Participants With Any Serious Adverse Event During the Follow-up Period
A serious adverse event is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should have been exercised in other situations. Refer to the general SAE module for a list of SAEs.
Time frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from Last Subject Last Visit [LSLV])
Number of Participants With Immunoglobulin Values Outside the Reference Range During the Follow-up Period
The reference ranges for immunoglobulins (LLN, ULN) are defined as: IgA (grams/Liter): 0.81, 4.63; IgG (grams/Liter): 6.94, 16.18; IgM (grams/Liter): 0.48, 2.71.
Time frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV)
Time to First CD19+ B-cell Repopulation Relative to the First Dose and Last Dose of Ofatumumab
Time to first CD19+ B-cell repopulation (return to normal or baseline level) relative to the first dose was assessed only for those participants whose B-cells repopulated after receiving ofatumumab. Time to first CD19+ B-cell repopulation relative to the last dose of ofatumumab was assessed only for those participants whose B-cells repopulated during their last ofatumumab treatment course or follow-up.
Time frame: From the first dose of ofatumumab until the last Follow-up Period visit (up to Week 248)
Number of Participants With a Positive JC Virus Test Result During the Follow-up Period
Blood samples were collected for analysis of plasma/white blood cell JC Virus (JCV) using the polymerase chain reaction (PCR) assay. Positive JC Virus test result indicated presence of JC Virus.
Time frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV)
Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern During the Follow-up Period
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low \[relative to the lower limit of normal\], CC High \[relative to the upper limit of normal\]) are: ALT: NA, 2; ALP: NA, 1.5; TBIL: NA, 1.5; CO2/BCO: 0.85, 1.2; CK: NA, 2; GGT: NA, 2; Urea/BUN: NA, 1.5.
Time frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years)
Number of Participants With the Indicated Hematology Values of Potential Clinical Concern During the Follow-up Period
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low \[relative to lower limit of normal\], CC High \[relative to upper limit of normal\]) are: Eosinophils: NA, 2; Total neutrophils: 0.8, 1.6; Platelet count: 0.65, 1.5.
Time frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years)