Lymphoma, Non-Hodgkin
Conditions
Keywords
CD20 Positive B-cell Non-Hodgkin Lymphoma, ABP 798
Brief summary
This was a randomized, double-blind, active-controlled, multiple-dose, clinical similarity study to evaluate the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability and immunogenicity of ABP 798 compared with rituximab in subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden. Subjects were randomized in a 1:1 ratio to receive a 375 mg/m\^2 intravenous infusion of either ABP 798 or rituximab once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Interventions
BIOLOGICALABP 798
ABP 798 was supplied as a sterile, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.
BIOLOGICALRituximab
Rituximab was procured from commercial supplies in the US and was supplied as a sterile, clear, colorless, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100-mg/10 mL or 500-mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females 18 years of age and older * Histological confirmed (by lymph node or extranodal region biopsy), Grade 1, 2, or 3a follicular B-cell NHL expressing CD20 within 12 months before randomization * Stage 2, 3, or 4 (per Cotswold's Modification of Ann Arbor Staging System) with measurable disease (per International Working Group) * subjects must have a baseline scan (computed tomography \[CT\]) of the neck (if palpable lymph node \> 1.0 cm), chest, abdomen, and pelvis to assess disease burden within 6 weeks before randomization * subjects must have had a baseline bone marrow biopsy within 12 months before randomization. Previously confirmed positive bone marrow involvement does not need to be repeated for purposes of screening. * Low tumor burden based on the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria * largest nodal or extranodal mass ≤ 7 cm * no more than 3 nodal sites with diameter \> 3 cm * no splenomegaly \> 16cm by CT scan and no symptomatic splenomegaly * no significant pleural or peritoneal serous effusions by CT * lactate dehydrogenase ≤ upper limit of normal (ULN) * no B symptoms (night sweats, fever \[temperature \> 38°C\], weight loss \> 10% in the previous 6 months)
Exclusion criteria
* Diffuse large cell component and/or Grade 3b follicular NHL * History or known presence of central nervous system metastases * Malignancy other than NHL within 5 years (except treated in-situ cervical cancer, or squamous or basal cell carcinoma of the skin) * Recent infection requiring a course of systemic anti-infective agents that was completed ≤ 7 days before randomization (with the exception of uncomplicated urinary tract infection) * Other investigational procedures that can impact the study data, results, or patient safety while participating in this study are excluded; participation in observational studies is allowed. * Subject is currently enrolled in or has not yet completed at least 30 days or 5 half-lives (whichever is longer) since ending other investigational device or drug study(s), including vaccines, or subject is receiving other investigational agent(s) * Previous use of either commercially available or investigational chemotherapy, biological, or immunological therapy for NHL (including rituximab or biosimilar rituximab, or other anti-CD20 treatments) * Systemic corticosteroid use within 3 months before randomization (inhaled are allowable)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease | Post treatment up to Week 28 | Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria \[Cheson et al, 1999\]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by \>75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; \>=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease | Week 12 | Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria \[Cheson et al, 1999\]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by \>75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; \>=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease. |
| Pharmacokinetic Serum Concentrations by Visit | Weeks 2, 3, 4, 12 and 20 | Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations \>0. |
| Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8 | Baseline (Day 1), Study Day 8 | Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts \< 20 cell/μL (0.02 \* 10\^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count \< 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count. |
| Total Immunoglobulin G (IgG) Results by Visit | Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28 | Samples were analyzed by a central lab. |
| Total Immunoglobulin M (IgM) Results by Visit | Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28 | Samples were analyzed by a central lab. |
| Participants With Treatment-Emergent Adverse Events | Day 1 (post treatment) to Week 28 | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. IP = investigational product |
| Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Day 1 (post treatment) to Week 28 | The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome. Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date. |
| Number of Participants Who Developed Anti-drug Antibodies | Baseline (Day 1), Weeks 12, 20 and 28 | Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay). Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point. |
| Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease | Day 1 up to Week 28 | PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review. |
| Percentage of Participants Who Survived -- Overall Survival (OS) | Day 1 up to Week 28 | Percentage of participants who were alive at the end of the study. |
Countries
Australia, Bulgaria, Canada, Colombia, Czechia, France, Georgia, Germany, Greece, India, Israel, Italy, Japan, Mexico, Poland, Romania, South Korea, Spain, Ukraine, United States
Participant flow
Recruitment details
A total of 380 subjects were screened and 256 participants (128 in the ABP 798 treatment group and 128 in the rituximab treatment group) were randomized at 91 centers across 20 countries.
Pre-assignment details
Participants were randomized centrally to receive either ABP 798 or rituximab in a 1:1 manner. The randomization was stratified based on geographic region (Europe, Americas, Japan, Asia Pacific - Other) and age group (\> 60 years of age, ≤ 60 years of age).
Participants by arm
| Arm | Count |
|---|---|
| ABP 798 ABP 798 was administered at a dose of 375 mg/m\^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20. | 128 |
| Rituximab Rituximab was administered at a dose of 375 mg/m\^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20. | 128 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Disease progression | 4 | 0 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | ABP 798 | Total | Rituximab |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 12.72 | 57.9 years STANDARD_DEVIATION 12.45 | 58.2 years STANDARD_DEVIATION 12.2 |
| Age, Customized <= 60 years | 71 Participants | 141 Participants | 70 Participants |
| Age, Customized > 60 years | 57 Participants | 115 Participants | 58 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 107 Participants | 217 Participants | 110 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 21 Participants | 39 Participants | 18 Participants |
| Height | 166.81 cm STANDARD_DEVIATION 10.737 | 167.22 cm STANDARD_DEVIATION 10.506 | 167.64 cm STANDARD_DEVIATION 10.292 |
| Previous Radiation Treatment No | 125 Participants | 250 Participants | 125 Participants |
| Previous Radiation Treatment Yes | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian, Japanese | 7 Participants | 15 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian, Non-Japanese | 17 Participants | 31 Participants | 14 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants | 15 Participants | 7 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Not allowed to collect | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 119 Participants | 238 Participants | 119 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 102 Participants | 203 Participants | 101 Participants |
| Race/Ethnicity, Customized White, Asian-Non-Japanese | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Americas | 10 Participants | 21 Participants | 11 Participants |
| Region of Enrollment Asia Pacific - Other | 23 Participants | 46 Participants | 23 Participants |
| Region of Enrollment Europe | 88 Participants | 174 Participants | 86 Participants |
| Region of Enrollment Japan | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Female | 68 Participants | 130 Participants | 62 Participants |
| Sex: Female, Male Male | 60 Participants | 126 Participants | 66 Participants |
| Time Since Original Diagnosis | 6.31 months STANDARD_DEVIATION 16.325 | 5.74 months STANDARD_DEVIATION 13.59 | 5.17 months STANDARD_DEVIATION 10.181 |
| Weight | 75.29 kg STANDARD_DEVIATION 19.135 | 75.24 kg STANDARD_DEVIATION 18.063 | 75.19 kg STANDARD_DEVIATION 16.981 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 128 | 0 / 126 |
| other Total, other adverse events | 59 / 128 | 61 / 126 |
| serious Total, serious adverse events | 5 / 128 | 5 / 126 |
Outcome results
Primary
Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease
Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria \[Cheson et al, 1999\]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by \>75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; \>=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.
Time frame: Post treatment up to Week 28
Population: The modified full analysis set included all randomized participants with evidence of disease at baseline per the tumor assessment from the central, independent, blinded assessments. Analyses for the modified full analysis set was based on randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 798 | Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease | 78.0 percentage of participants |
| Rituximab | Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease | 70.2 percentage of participants |
90% CI: [-1.4, 16.8]
95% CI: [-3.2, 18.6]
Secondary
Number of Participants Who Developed Anti-drug Antibodies
Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay). Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point.
Time frame: Baseline (Day 1), Weeks 12, 20 and 28
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABP 798 | Number of Participants Who Developed Anti-drug Antibodies | Binding antibody positive | 3 Participants |
| ABP 798 | Number of Participants Who Developed Anti-drug Antibodies | Neutralizing antibody positive | 1 Participants |
| Rituximab | Number of Participants Who Developed Anti-drug Antibodies | Binding antibody positive | 1 Participants |
| Rituximab | Number of Participants Who Developed Anti-drug Antibodies | Neutralizing antibody positive | 1 Participants |
Secondary
Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease
PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.
Time frame: Day 1 up to Week 28
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 798 | Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease | Participants with disease progression or death | 3.1 percentage of participants |
| ABP 798 | Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease | Participants alive and progression-free | 96.9 percentage of participants |
| Rituximab | Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease | Participants with disease progression or death | 2.4 percentage of participants |
| Rituximab | Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease | Participants alive and progression-free | 97.6 percentage of participants |
Secondary
Participants With Treatment-Emergent Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. IP = investigational product
Time frame: Day 1 (post treatment) to Week 28
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABP 798 | Participants With Treatment-Emergent Adverse Events | Any AE | 107 Participants |
| ABP 798 | Participants With Treatment-Emergent Adverse Events | Any grade >=3 AE | 14 Participants |
| ABP 798 | Participants With Treatment-Emergent Adverse Events | Any fatal AE | 0 Participants |
| ABP 798 | Participants With Treatment-Emergent Adverse Events | Any serious AE | 5 Participants |
| ABP 798 | Participants With Treatment-Emergent Adverse Events | Any AE leading to discontinuation of IP | 4 Participants |
| ABP 798 | Participants With Treatment-Emergent Adverse Events | Any AE leading to dose delay/withheld IP | 9 Participants |
| Rituximab | Participants With Treatment-Emergent Adverse Events | Any AE leading to discontinuation of IP | 1 Participants |
| Rituximab | Participants With Treatment-Emergent Adverse Events | Any AE | 95 Participants |
| Rituximab | Participants With Treatment-Emergent Adverse Events | Any serious AE | 5 Participants |
| Rituximab | Participants With Treatment-Emergent Adverse Events | Any grade >=3 AE | 13 Participants |
| Rituximab | Participants With Treatment-Emergent Adverse Events | Any AE leading to dose delay/withheld IP | 9 Participants |
| Rituximab | Participants With Treatment-Emergent Adverse Events | Any fatal AE | 0 Participants |
Secondary
Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease
Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria \[Cheson et al, 1999\]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by \>75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; \>=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.
Time frame: Week 12
Population: The modified full analysis set included all randomized participants with evidence of disease at baseline per the tumor assessment from the central, independent, blinded assessments. Analyses for the modified full analysis set was based on randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 798 | Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease | 59.3 percentage of participants |
| Rituximab | Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease | 58.1 percentage of participants |
Comparison: The 2-sided 90% confidence limits of the risk difference (RD) of ORR at week 12 used a generalized linear model adjusted for the stratification factors (geographic region and age group).90% CI: [-9.3, 11.2]
Comparison: The 2-sided 95% confidence limits of the risk difference (RD) of ORR at week 12 used a generalized linear model adjusted for the stratification factors (geographic region and age group).95% CI: [-11.3, 13.2]
Secondary
Percentage of Participants Who Survived -- Overall Survival (OS)
Percentage of participants who were alive at the end of the study.
Time frame: Day 1 up to Week 28
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 798 | Percentage of Participants Who Survived -- Overall Survival (OS) | 100 percentage of participants |
| Rituximab | Percentage of Participants Who Survived -- Overall Survival (OS) | 100 percentage of participants |
Secondary
Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8
Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts \< 20 cell/μL (0.02 \* 10\^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count \< 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.
Time frame: Baseline (Day 1), Study Day 8
Population: Full analysis set of participants with available data. Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count \< 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 798 | Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8 | 98.3 percentage of participants |
| Rituximab | Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8 | 98.3 percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs)
The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome. Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date.
Time frame: Day 1 (post treatment) to Week 28
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Any AEOI | 49.2 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Infusion reactions including hypersensitivity | 43.0 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Hematological reactions | 5.5 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Cardiac disorders | 2.3 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Serious infections | 1.6 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Severe mucocutaneous reactions | 0.8 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Gastrointestinal perforation | 0 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Hepatitis B reactivation | 0 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Opportunistic infection | 0 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Progressive multifocal leukoencephalopathy | 0 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Reversible posterior leukoencephalopathy | 0 percentage of participants |
| ABP 798 | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Tumor lysis syndrome | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Reversible posterior leukoencephalopathy | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Any AEOI | 45.2 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Gastrointestinal perforation | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Infusion reactions including hypersensitivity | 42.9 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Progressive multifocal leukoencephalopathy | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Hematological reactions | 4.8 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Hepatitis B reactivation | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Cardiac disorders | 1.6 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Tumor lysis syndrome | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Serious infections | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Opportunistic infection | 0 percentage of participants |
| Rituximab | Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | Severe mucocutaneous reactions | 0 percentage of participants |
Comparison: Percentage risk difference for 'Any adverse event of interest'95% CI: [-8.3, 16.3]
Comparison: Percentage risk difference for 'Infusion reactions including hypersensitivity'95% CI: [-12.1, 12.3]
Comparison: Percentage risk difference for 'Hematological reactions'95% CI: [-11.8, 13]
Comparison: Percentage risk difference in 'Cardiac disorders'95% CI: [-11.8, 13.2]
Comparison: Percentage risk difference in 'Serious infections'95% CI: [-10.9, 14]
Comparison: Percentage risk difference in 'Severe mucocutaneous reactions'95% CI: [-11.7, 13.2]
Secondary
Pharmacokinetic Serum Concentrations by Visit
Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations \>0.
Time frame: Weeks 2, 3, 4, 12 and 20
Population: Safety Analysis Set of participants with available data. Participants with PK concentrations below the lower limit of quantification (LLOQ) were excluded from these analyses.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 798 | Pharmacokinetic Serum Concentrations by Visit | Week 4 (predose) | 132.70 microgram/mL | Geometric Coefficient of Variation 42.6 |
| ABP 798 | Pharmacokinetic Serum Concentrations by Visit | Week 2 (predose) | 58.66 microgram/mL | Geometric Coefficient of Variation 50.4 |
| ABP 798 | Pharmacokinetic Serum Concentrations by Visit | Week 3 (predose) | 105.39 microgram/mL | Geometric Coefficient of Variation 37.8 |
| ABP 798 | Pharmacokinetic Serum Concentrations by Visit | Week 12 (predose) | 21.86 microgram/mL | Geometric Coefficient of Variation 156.1 |
| ABP 798 | Pharmacokinetic Serum Concentrations by Visit | Week 12 (postdose) | 207.05 microgram/mL | Geometric Coefficient of Variation 58.1 |
| ABP 798 | Pharmacokinetic Serum Concentrations by Visit | Week 20 (predose) | 13.37 microgram/mL | Geometric Coefficient of Variation 138.7 |
| Rituximab | Pharmacokinetic Serum Concentrations by Visit | Week 12 (postdose) | 209.14 microgram/mL | Geometric Coefficient of Variation 66.8 |
| Rituximab | Pharmacokinetic Serum Concentrations by Visit | Week 4 (predose) | 140.23 microgram/mL | Geometric Coefficient of Variation 57.9 |
| Rituximab | Pharmacokinetic Serum Concentrations by Visit | Week 12 (predose) | 20.55 microgram/mL | Geometric Coefficient of Variation 194.1 |
| Rituximab | Pharmacokinetic Serum Concentrations by Visit | Week 2 (predose) | 58.63 microgram/mL | Geometric Coefficient of Variation 76.9 |
| Rituximab | Pharmacokinetic Serum Concentrations by Visit | Week 20 (predose) | 16.45 microgram/mL | Geometric Coefficient of Variation 115.8 |
| Rituximab | Pharmacokinetic Serum Concentrations by Visit | Week 3 (predose) | 108.77 microgram/mL | Geometric Coefficient of Variation 59.1 |
Secondary
Total Immunoglobulin G (IgG) Results by Visit
Samples were analyzed by a central lab.
Time frame: Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Population: Full analysis set of participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 798 | Total Immunoglobulin G (IgG) Results by Visit | Day 8 (Week 2) | 9.790 g/L | Standard Deviation 2.5719 |
| ABP 798 | Total Immunoglobulin G (IgG) Results by Visit | Week 4 | 9.744 g/L | Standard Deviation 2.5805 |
| ABP 798 | Total Immunoglobulin G (IgG) Results by Visit | Week 3 | 9.545 g/L | Standard Deviation 2.5933 |
| ABP 798 | Total Immunoglobulin G (IgG) Results by Visit | Week 28 | 9.846 g/L | Standard Deviation 2.6316 |
| ABP 798 | Total Immunoglobulin G (IgG) Results by Visit | Baseline | 9.740 g/L | Standard Deviation 2.5988 |
| Rituximab | Total Immunoglobulin G (IgG) Results by Visit | Week 28 | 10.281 g/L | Standard Deviation 2.3617 |
| Rituximab | Total Immunoglobulin G (IgG) Results by Visit | Baseline | 10.570 g/L | Standard Deviation 2.597 |
| Rituximab | Total Immunoglobulin G (IgG) Results by Visit | Day 8 (Week 2) | 10.486 g/L | Standard Deviation 2.4916 |
| Rituximab | Total Immunoglobulin G (IgG) Results by Visit | Week 3 | 10.374 g/L | Standard Deviation 2.3214 |
| Rituximab | Total Immunoglobulin G (IgG) Results by Visit | Week 4 | 10.196 g/L | Standard Deviation 2.2842 |
Secondary
Total Immunoglobulin M (IgM) Results by Visit
Samples were analyzed by a central lab.
Time frame: Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Population: Full analysis set of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 798 | Total Immunoglobulin M (IgM) Results by Visit | Day 8 (Week 2) | 1.004 g/L | Standard Deviation 1.03 |
| ABP 798 | Total Immunoglobulin M (IgM) Results by Visit | Week 4 | 0.985 g/L | Standard Deviation 1.0459 |
| ABP 798 | Total Immunoglobulin M (IgM) Results by Visit | Week 3 | 1.001 g/L | Standard Deviation 1.0564 |
| ABP 798 | Total Immunoglobulin M (IgM) Results by Visit | Week 28 | 0.816 g/L | Standard Deviation 0.8505 |
| ABP 798 | Total Immunoglobulin M (IgM) Results by Visit | Baseline | 1.021 g/L | Standard Deviation 1.0072 |
| Rituximab | Total Immunoglobulin M (IgM) Results by Visit | Week 28 | 1.127 g/L | Standard Deviation 3.6752 |
| Rituximab | Total Immunoglobulin M (IgM) Results by Visit | Baseline | 1.247 g/L | Standard Deviation 3.4018 |
| Rituximab | Total Immunoglobulin M (IgM) Results by Visit | Day 8 (Week 2) | 1.280 g/L | Standard Deviation 3.7292 |
| Rituximab | Total Immunoglobulin M (IgM) Results by Visit | Week 3 | 1.370 g/L | Standard Deviation 5.025 |
| Rituximab | Total Immunoglobulin M (IgM) Results by Visit | Week 4 | 1.385 g/L | Standard Deviation 5.3266 |