Waldenstrom Macroglobulinaemia
Conditions
Keywords
Waldenstrom's Macroglobulinemia, Ofatumumab
Brief summary
Given the tolerability and efficacy of ofatumumab in follicular lymphoma and Chronic Lymphocytic Leukemia, and the need to improve therapy for patients with WM utilizing a non-myelosuppressive agent this phase II trial of ofatumumab is being initiated in patients with Waldenstrom's Macroglobulinemia (WM).
Interventions
BIOLOGICALOfatumumab
Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed and active Waldenstrom's Macroglobulinemia requiring treatment. * Ambulatory and capable of all selfcare. Up and about more than 50% of waking hours. * Adequate organ function. * Detectable CD20 positive of the tumor cells. * Measurable disease as defined by a monoclonal IgM paraprotein level greater than 1000 mg/dL.
Exclusion criteria
* Treatment of WM within the past 28 days. * Treatment with rituximab or alemtuzamab within the past 3 months. * Certain heart problems, chronic or current active infection not controlled with oral antibiotics, other current cancer or within last 5 years. * Current participation in another interventional clinical study. * Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception. * Active cerebrovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment | OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline. |
| Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | Baseline and up to Study Week 16 | OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment | IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by \>25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of \>25% from BL. |
| Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator | From baseline up to approximately 5 years | Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node \>=1.5 centimeters on any axis. Progression for PR/MR is either a \>=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM. |
| Progression-free Survival | From baseline up to approximately 5 years | Time to disease progression is defined as the time from baseline to disease progression or death. |
| Time to Response for Responders | From baseline up to approximately 5 years | Time to response is defined as the time from baseline to the first response date. |
| Overall Survival | From baseline up to approximately 5 years | Overall survival is defined as the time from baseline until death due to any cause. |
| Clearance of Ofatumumab | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 | Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. |
| Volume of Distribution at Steady State of Ofatumumab | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 | Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. |
| Half-life of Ofatumumab | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 | Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. |
| Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment | Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline. |
| AUC(0-tau) and AUC(0-inf) of Ofatumumab | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 | AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. |
| Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result | From baseline up to approximately 5 years | All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive. |
| Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | Baseline and Month 3 | CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants With the Indicated SAEs Related to Study Drug | From baseline up to approximately 5 years | An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement. |
| Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | From baseline up to approximately 5 years | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug. |
| Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | From baseline up to approximately 5 years | Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study. |
| Number of Participants With the Indicated >=Grade 3 AEs | From baseline up to approximately 5 years | AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. |
| Number of Participants With the Indicated Infusion-related >=Grade 3 AE | From baseline up to approximately 5 years | Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. |
| Cmax and Ctrough of Ofatumumab | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 | Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. |
| Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | Baseline and up to Study Week 16 | Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks \[Weeks (Wk.) 1 through 4\]) (300 milligrams \[mg\] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5. | 15 |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks \[Weeks 1 through 5\]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5. | 22 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator Discretion | 10 | 8 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Total | 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 |
|---|---|---|---|
| Age, Continuous | 62.3 Years STANDARD_DEVIATION 10.78 | 63.3 Years STANDARD_DEVIATION 9.85 | 64.0 Years STANDARD_DEVIATION 9.36 |
| Race/Ethnicity, Customized African American/African Heritage | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized White - White/Caucasian/European | 14 participants | 33 participants | 19 participants |
| Sex: Female, Male Female | 6 Participants | 15 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 22 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 15 | 20 / 22 |
| serious Total, serious adverse events | 5 / 15 | 7 / 22 |
Outcome results
Primary
Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator
OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline.
Time frame: Baseline and up to Study Week 16
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | 5 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | 14 participants |
95% CI: [11.8, 61.6]
95% CI: [40.7, 82.8]
Primary
Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator
OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline.
Time frame: Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Population: Intent-to-Treat (ITT) Population: all participants who were considered eligible for treatment and who had been exposed to study drug irrespective of the planned course of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | 7 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | 15 participants |
95% CI: [21.3, 73.4]
95% CI: [45.1, 86.1]
Secondary
AUC(0-tau) and AUC(0-inf) of Ofatumumab
AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Population: PK Population. Data were provided for the number of participants attending each visit for whom the parameter could be calculated..
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-inf), Course 2 Dose 5, n=8,12 | 221675 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau), Course 1 Dose 5, n=0,18 | NA micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-inf), Course 1 Dose 4, n=9,0 | 120886 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-inf), Course 1 Dose 5, n=0,18 | NA micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau), Course 2 Dose 5, n=10,12 | 61259 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau), Course 1 Dose 4, n=13,0 | 21419 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-inf), Course 1 Dose 5, n=0,18 | 392012 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau), Course 2 Dose 5, n=10,12 | 106275 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-inf), Course 1 Dose 4, n=9,0 | NA micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-inf), Course 2 Dose 5, n=8,12 | 507794 micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau), Course 1 Dose 4, n=13,0 | NA micrograms X hours/milliliters (µg.h/mL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau), Course 1 Dose 5, n=0,18 | 75526 micrograms X hours/milliliters (µg.h/mL) |
Secondary
Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment
CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Month 3
Population: ITT Population: only participants with blood count data at both Baseline and Month 3 were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD50 | 9 cells per microliter (µL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD4+ | -35.5 cells per microliter (µL) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD19+ | -26 cells per microliter (µL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD50 | -43 cells per microliter (µL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD4+ | 98 cells per microliter (µL) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD19+ | -24.5 cells per microliter (µL) |
Secondary
Clearance of Ofatumumab
Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Population: Pharmacokinetic (PK) Population: all participants from whom a PK sample was obtained and analyzed. Data were provided for the number of participants for whom the parameter could be determined.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Clearance of Ofatumumab | 27.9 milliliters/hour (ml/hr) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Clearance of Ofatumumab | 13.5 milliliters/hour (ml/hr) |
Secondary
Cmax and Ctrough of Ofatumumab
Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Population: PK Population. Data were provided for the number of participants attending each visit for whom the parameter could be determined.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 5, n=0,18 | NA micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 4, n=13,0 | 259 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 2 Dose 1, n=9,11 | 53.2 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 3, n=0,19 | NA micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 2 Dose 3, n=8,12 | 554 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 2, n=7,12 | 3.0 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 2 Dose 5, n=10,12 | 528 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 5, n=0,18 | NA micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 2, n=7,10 | 8.1 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 4, n=11,12 | 225 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 3, n=8,12 | 144 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 3, n=11,19 | 13.9 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 4, n=13,21 | 23.4 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 5, n=11,12 | 279 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 1, n=14,19 | 68.3 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 5, n=11,12 | 384 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 2, n=7,12 | 8.0 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 3, n=11,19 | 121 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 1, n=14,19 | 72.1 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 4, n=13,0 | NA micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 5, n=0,18 | 640 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 4, n=13,21 | 181 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 1 Dose 5, n=0,18 | 249 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 2 Dose 1, n=9,11 | 64.8 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 2 Dose 3, n=8,12 | 577 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 2 Dose 5, n=10,12 | 803 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 2, n=7,10 | 20.4 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 3, n=8,12 | 169 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Ctrough, Course 2 Dose 4, n=11,12 | 310 micrograms/milliliter (µg/ml) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Cmax and Ctrough of Ofatumumab | Cmax, Course 1 Dose 3, n=0,19 | 465 micrograms/milliliter (µg/ml) |
Secondary
Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator
Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node \>=1.5 centimeters on any axis. Progression for PR/MR is either a \>=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM.
Time frame: From baseline up to approximately 5 years
Population: ITT Population. Only those participants classified as responders were included in the analysis. Participants who had disease progression or death were counted as events, and other participants were censored at the date of the last adequate assessment in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator | 449.0 days |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator | 455.0 days |
Secondary
Half-life of Ofatumumab
Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Population: PK Population. Data were provided for the number of participants for whom the parameter could be determined.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Half-life of Ofatumumab | 10.9 Days (d) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Half-life of Ofatumumab | 23.9 Days (d) |
Secondary
Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result
All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive.
Time frame: From baseline up to approximately 5 years
Population: Safety Population. Only those participants with post-ofatumumab HAHA results were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result | 4 participants |
Secondary
Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator
Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline.
Time frame: Baseline and up to Study Week 16
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | CR | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | PR | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | MR | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | CR | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | PR | 9 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | MR | 5 participants |
Secondary
Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator
Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =\<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a \>=50% reduction from baseline in the SM IgM concentration. MR: \>=25%, but a \<50% reduction of SM IgM from baseline.
Time frame: Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | PR | 4 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | MR | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | CR | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | PR | 11 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | MR | 4 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | CR | 0 participants |
Secondary
Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle)
IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by \>25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of \>25% from BL.
Time frame: Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Population: ITT Population. Only those participants who received Cycle 1 treatment (including the Redosing Cycle) were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | >25% increase from BL, any response, n=15, 22 | 7 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | =<25% increase from BL, any response, n=15, 22 | 8 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | >25% increase from BL, PR/MR response , n=7, 15 | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | =<25% increase from BL, PR/MR response , n=7, 15 | 6 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | =<25% increase from BL, PR/MR response , n=7, 15 | 13 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | >25% increase from BL, any response, n=15, 22 | 9 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | >25% increase from BL, PR/MR response , n=7, 15 | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | =<25% increase from BL, any response, n=15, 22 | 13 participants |
Secondary
Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study
Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study.
Time frame: From baseline up to approximately 5 years
Population: Safety Population. Only those participants who experienced an AE leading to their withdrawal from the study were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Haemolytic anaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Renal failure acute | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Febrile neutropenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Myocardial ischaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Fluid overload | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Pulmonary oedema | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Fluid overload | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Myocardial ischaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Haemolytic anaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Pulmonary oedema | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Renal failure acute | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Febrile neutropenia | 0 participants |
Secondary
Number of Participants With the Indicated >=Grade 3 AEs
AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Time frame: From baseline up to approximately 5 years
Population: Safety Population. Only those participants who experienced a \>=Grade 3 AE were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Serum sickness | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Chest pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Dizziness | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Haemoglobin decreased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Headache | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Syncope | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Protein total increased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Myocardial ischaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Chest discomfort | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Abdominal discomfort | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Dyspnoea exertional | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Urinary tract infection | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Haemolytic anaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Fluid overload | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Epistaxis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Back pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Pyrexia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Renal failure acute | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Pulmonary oedema | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Rash | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Anaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Neutropenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Cryoglobulinaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Fatigue | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Blood creatinine increased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Small intestinal obstruction | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Febrile neutropenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Small intestinal obstruction | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Anaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Febrile neutropenia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Haemolytic anaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Chest pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Chest discomfort | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Pyrexia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Blood creatinine increased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Haemoglobin decreased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Protein total increased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Dyspnoea exertional | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Epistaxis | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Pulmonary oedema | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Cryoglobulinaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Serum sickness | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Dizziness | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Headache | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Syncope | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Myocardial ischaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Abdominal discomfort | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Urinary tract infection | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Fluid overload | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Back pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Renal failure acute | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Rash | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Neutropenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated >=Grade 3 AEs | Fatigue | 1 participants |
Secondary
Number of Participants With the Indicated Infusion-related >=Grade 3 AE
Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Time frame: From baseline up to approximately 5 years
Population: Safety Population. Only those participants who experienced \>=Grade 3 infusion-related AEs were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Chest pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Chest discomfort | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Back pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Rash | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Rash | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Chest pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Back pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Chest discomfort | 0 participants |
Secondary
Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug.
Time frame: From baseline up to approximately 5 years
Population: Safety Population. Only those participants who experienced a study drug-related AE were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Sneezing | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Flushing | 6 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Erythema | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypotension | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pyrexia | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Back pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Paraesthesia oral | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Limb discomfort | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Chills | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Muscle spasms | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Palmar erythema | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Musculoskeletal pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Chest pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Myalgia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Arthralgia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Trismus | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Chest discomfort | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Anaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rash macular | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Fatigue | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Leukopenia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Nasal congestion | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Neutropenia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Non-cardiac chest pain | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Ear pruritus | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Swelling face | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Eye pruritus | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Asthenia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Ocular hyperaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pruritus | 4 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Abnormal sensation in eye | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Ill-defined disorder | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Eye swelling | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Throat irritation | 7 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Decreased appetite | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Local swelling | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Fluid overload | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Epistaxis | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypophagia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Malaise | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Increased appetite | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Urticaria | 4 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Headache | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Paraesthesia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Oropharyngeal pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Sinus headache | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Abdominal pain | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Infusion related reaction | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Lymph node pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Blood creatinine increased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Diarrhoea | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Body temperature increased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Dyspnoea | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Protein total increased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Nausea | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypersensitivity | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pruritus generalised | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Serum sickness | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Painful respiration | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rhinitis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Abdominal discomfort | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Urinary tract infection | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rhinorrhoea | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Insomnia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Dyspepsia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Renal failure acute | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pulmonary oedema | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Thirst | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypoaesthesia oral | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Vomiting | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hyperhidrosis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Cryoglobulinaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Lip swelling | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pallor | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rhinitis allergic | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Oral pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Fluid retention | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Bradycardia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypoaesthesia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Oral pruritus | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Psychomotor hyperactivity | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Stomatitis | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Weight decreased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rash | 4 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Weight decreased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rash | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Dyspnoea | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rhinitis allergic | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Oral pruritus | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Lymph node pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Bradycardia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pruritus | 8 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Urticaria | 9 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pruritus generalised | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hyperhidrosis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Erythema | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Palmar erythema | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rash macular | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Swelling face | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Throat irritation | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Nasal congestion | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Oropharyngeal pain | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Epistaxis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Painful respiration | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pulmonary oedema | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rhinorrhoea | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Sneezing | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pyrexia | 5 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Chills | 5 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Chest pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Chest discomfort | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Fatigue | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Non-cardiac chest pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Asthenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Ill-defined disorder | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Local swelling | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Malaise | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Abdominal pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Diarrhoea | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Nausea | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Paraesthesia oral | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Abdominal discomfort | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Dyspepsia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypoaesthesia oral | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Lip swelling | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Oral pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Stomatitis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Flushing | 4 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypotension | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Back pain | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Limb discomfort | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Muscle spasms | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Musculoskeletal pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Myalgia | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Trismus | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Anaemia | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Leukopenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Neutropenia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Ear pruritus | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Eye pruritus | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Ocular hyperaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Abnormal sensation in eye | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Eye swelling | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Decreased appetite | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Fluid overload | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypophagia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Increased appetite | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Headache | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Paraesthesia | 2 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Sinus headache | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Infusion related reaction | 3 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Blood creatinine increased | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Body temperature increased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Protein total increased | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypersensitivity | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Serum sickness | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Rhinitis | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Urinary tract infection | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Insomnia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Renal failure acute | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Thirst | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Vomiting | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Cryoglobulinaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Pallor | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Arthralgia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Fluid retention | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Hypoaesthesia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | Psychomotor hyperactivity | 1 participants |
Secondary
Number of Participants With the Indicated SAEs Related to Study Drug
An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Time frame: From baseline up to approximately 5 years
Population: Safety Population. Only those participants who experienced an SAE categorized as being related to study drug were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Fluid overload | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Haemolysis | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Chest pain | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Cryoglobulinaemia | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Renal failure acute | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Pulmonary oedema | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Renal failure acute | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Fluid overload | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Cryoglobulinaemia | 0 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Haemolysis | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Pulmonary oedema | 1 participants |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Number of Participants With the Indicated SAEs Related to Study Drug | Chest pain | 1 participants |
Secondary
Overall Survival
Overall survival is defined as the time from baseline until death due to any cause.
Time frame: From baseline up to approximately 5 years
Population: ITT Population. Only those participants who died during the study and during the follow-up period were assessed.
Secondary
Progression-free Survival
Time to disease progression is defined as the time from baseline to disease progression or death.
Time frame: From baseline up to approximately 5 years
Population: ITT Population. Participants who experienced disease progression or death were counted as events, and other participants were censored at the time of the last adequate assessment in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Progression-free Survival | 558.0 days |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Progression-free Survival | 536.0 days |
Secondary
Time to Response for Responders
Time to response is defined as the time from baseline to the first response date.
Time frame: From baseline up to approximately 5 years
Population: ITT Population. Only participants classified as responders (CR, PR, and MR) were assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Time to Response for Responders | 78 days |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Time to Response for Responders | 81 days |
Secondary
Volume of Distribution at Steady State of Ofatumumab
Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Population: PK Population. Data were provided for the number of participants for whom the parameter could be determined.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Volume of Distribution at Steady State of Ofatumumab | 10.0 Liters (L) |
| 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Volume of Distribution at Steady State of Ofatumumab | 10.7 Liters (L) |