Arthritis, Rheumatoid
Conditions
Brief summary
This trial is designed to determine what effects the human body has on the investigational medicine, ABP 798, and what effects the body has on the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, rituximab, in patients with moderate or severe RA. This study will also assess if the investigational medicine is safe and effective in treating moderate or severe RA compared to the licensed medicine.
Interventions
DRUGABP 798
Supplied as a 10 mg/mL liquid concentrate for intravenous (IV) administration.
DRUGRituximab (US)
Supplied as a 10 mg/mL liquid concentrate for IV administration.
DRUGRituximab (EU)
Supplied as a 10 mg/mL liquid concentrate for IV administration.
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Men or women ≥ 18 and ≤ 80 years old * Subjects must be diagnosed with rheumatoid arthritis for at least 6 months before baseline * Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline and at least one of the following at screening: * erythrocyte sedimentation rate (ESR) ≥ 28 mm/hr * serum C-reactive protein (CRP) \> 1.0 mg/dL * Subjects must be taking methotrexate (MTX) for ≥ 12 consecutive weeks and on a stable dose of MTX 7.5 to 25 mg/week for ≥ 8 weeks prior to receiving the investigational product (IP), and be willing to remain on a stable dose throughout the study * Subject has no known history of active tuberculosis
Exclusion criteria
* Class IV RA, Felty's syndrome or history of prosthetic or native joint infection * Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome * Use of commercially available or investigational biologic therapies for RA as follows: * anakinra, etanercept within 1 month prior to first dose of IP * infliximab, abatacept, tocilizumab, golimumab, certolizumab within 3 months prior to first dose of IP * other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) prior to first dose of IP * Previous receipt of rituximab or a biosimilar of rituximab Other Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose | Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose. | Area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUCinf was estimated using the linear trapezoidal rule. |
| Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose | Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose. | Maximum observed concentration following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose. | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast) | Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Terminal Elimination Half-life (t1/2) | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Terminal Elimination Rate Constant (λz) | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57 and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Clearance (CL) | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Mean Residence Time (MRT) | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Percent of AUC Extrapolation (AUC%Extrap) | Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Percent of AUC extrapolated to infinity in AUCinf. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| AUC0-12 wk/AUCinf | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12). | Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. |
| Change From Baseline in Disease Activity Score 28-CRP at Week 24 | Baseline and Week 24 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count * 28 swollen joint count * C-reactive protein (CRP) * Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day) | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose. | Area under the serum concentration-time curve from time 0 on day 1 prior to the first infusion of the first dose to 14 days postdose. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUC0-14day was estimated using the linear trapezoidal rule. |
| Percentage of Participants With an ACR20 Response | Baseline and Weeks 8, 12, 24, 40, and 48 | A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global health assessment (measured on a 100 mm VAS); * Investigator's global health assessment (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-reactive protein concentration. |
| Percentage of Participants With an ACR50 Response | Baseline and Weeks 8, 12, 24, 40, and 48 | A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global health assessment (measured on a 100 mm VAS); * Investigator's global health assessment (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-reactive protein concentration. |
| Percentage of Participants With an ACR70 Response | Baseline and Weeks 8, 12, 24, 40, and 48 | A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: * Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global health assessment (measured on a 100 mm VAS); * Investigator's global health assessment (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-reactive protein concentration. |
| Hybrid ACR | Baseline and weeks 8, 12, 24, 40, and 48 | The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Investigator's Global Assessment of Disease Activity, disability index of the HAQ, and CRP) was calculated (a positive change indicates improvement, and the maximum worst change is limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement). |
| Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3 | Day 3 | Complete depletion of cluster of differentiation (CD) 19 positive cells was defined as a CD19+ cell count \< 20 cell/μL (0.02 x 10⁹ cell/L). |
| Duration of Complete Depletion in CD19+ Cell Count | CD19+ cell count was assessed at baseline, days 2, 3, weeks 4, 24, and 48 | Duration of CD19+ B-cell complete depletion was defined as the time from the first incidence of complete depletion of CD19+ cell count (CD19+ cell count \< 20 cells/μL) to when the CD19+ cell count first increased to ≥ 20 cells/μL. Participants whose CD19+ cell count did not increase to ≥ 20 cells/μL were censored at the last CD19+ assessment date. |
| Number of Participants With Adverse Events After the First Dose | From day 1 until the first infusion of the second dose (week 24) | Adverse events (AEs) were graded by the investigator according to National Cancer Institute 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 AE, and Grade 5 = death due to AE. A serious AE (SAE) was defined as an AE that met at least 1 of the following serious criteria: * fatal * life-threatening * required inpatient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. The adverse events of interest prespecified for this study included infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, hypogammaglobulinemia, severe mucocutaneous reactions, and gastrointestinal perforation. |
| Number of Participants Who Developed Anti-drug Antibodies | Day 1 through the end of study (48 weeks). | 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. |
| Number of Participants With Clinically Significant Laboratory Findings | Day 1 through the end of study (48 weeks). | Clinically significant clinical laboratory findings were defined as laboratory results that were ≥ Grade 3, based on the CTCAE version 4.03. |
| Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Baseline and weeks 8, 12, 40, and 48 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count * 28 swollen joint count * C-reactive protein (CRP) * Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk) | Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hour postdose, and at days 29, 57, and 85 (week 12). | Area under the serum concentration-time curve from time 0 on day 1 prior to the first infusion of the first dose to week 12. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUC0-12wk was estimated using the linear trapezoidal rule. |
Countries
Bulgaria, Estonia, Germany, Hungary, Poland, United States
Participant flow
Recruitment details
This study was conducted at 57 centers in Bulgaria, Estonia, Germany, Hungary, Poland, and the United States (US). Eligible participants were men and women aged 18 to 80 years, inclusive, with a diagnosis of rheumatoid arthritis (RA) for at least 6 months.
Pre-assignment details
Participants were randomized in a 1:1:1 ratio to 1 of 3 groups, stratified by geographic region (North America vs Eastern Europe vs Western Europe), seropositivity (rheumatoid factor \[RF\]-positive and/or cyclic citrullinated peptide \[CCP\]-positive vs RF-negative and CCP-negative), and number of prior biologic therapies used for RA (1 vs \> 1).
Participants by arm
| Arm | Count |
|---|---|
| ABP 798 / ABP 798 Participants received ABP 798 on days 1 and 15 (dose 1) and a second dose of ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart. | 104 |
| Rituximab (EU) / Rituximab (EU) Participants received rituximab (EU formulation) on days 1 and 15 (dose 1) and a second dose of rituximab (EU formulation) at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart. | 104 |
| Rituximab (US) / ABP 798 Participants received rituximab (US formulation) on days 1 and 15 (dose 1) and transitioned to receive ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart. | 103 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 4 |
| Overall Study | Dissatisfaction with Treatment Efficacy | 1 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 3 |
Baseline characteristics
| Characteristic | Rituximab (US) / ABP 798 | ABP 798 / ABP 798 | Rituximab (EU) / Rituximab (EU) | Total |
|---|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 10.66 | 54.6 years STANDARD_DEVIATION 10.7 | 56.8 years STANDARD_DEVIATION 11.34 | 55.9 years STANDARD_DEVIATION 10.91 |
| Age, Customized < 65 years | 78 Participants | 87 Participants | 74 Participants | 239 Participants |
| Age, Customized ≥ 65 years | 25 Participants | 17 Participants | 30 Participants | 72 Participants |
| Disease Activity Score 28 - C-Reactive Protein (DAS28[CRP]) | 6.03 scores on a scale STANDARD_DEVIATION 0.997 | 6.09 scores on a scale STANDARD_DEVIATION 1.035 | 5.84 scores on a scale STANDARD_DEVIATION 1.006 | 5.99 scores on a scale STANDARD_DEVIATION 1.015 |
| Duration of RA | 12.48 years STANDARD_DEVIATION 9.186 | 11.37 years STANDARD_DEVIATION 7.4 | 11.69 years STANDARD_DEVIATION 7.945 | 11.84 years STANDARD_DEVIATION 8.194 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 8 Participants | 10 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants | 96 Participants | 94 Participants | 282 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region Eastern Europe | 59 Participants | 59 Participants | 58 Participants | 176 Participants |
| Geographic Region North America | 39 Participants | 38 Participants | 40 Participants | 117 Participants |
| Geographic Region Western Europe | 5 Participants | 7 Participants | 6 Participants | 18 Participants |
| Prior Biologic Use for RA More than one | 40 Participants | 42 Participants | 43 Participants | 125 Participants |
| Prior Biologic Use for RA One | 63 Participants | 62 Participants | 61 Participants | 186 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 5 Participants | 3 Participants | 18 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 91 Participants | 97 Participants | 99 Participants | 287 Participants |
| Seropositivity RF negative and CCP negative | 14 Participants | 18 Participants | 16 Participants | 48 Participants |
| Seropositivity RF positive and/or CCP positive | 89 Participants | 86 Participants | 88 Participants | 263 Participants |
| Sex: Female, Male Female | 83 Participants | 90 Participants | 91 Participants | 264 Participants |
| Sex: Female, Male Male | 20 Participants | 14 Participants | 13 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 0 / 104 | 0 / 103 | 0 / 104 | 0 / 104 | 0 / 103 |
| other Total, other adverse events | 21 / 104 | 15 / 104 | 14 / 103 | 38 / 104 | 22 / 104 | 19 / 103 |
| serious Total, serious adverse events | 4 / 104 | 5 / 104 | 5 / 103 | 8 / 104 | 8 / 104 | 8 / 103 |
Outcome results
Primary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose
Area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUCinf was estimated using the linear trapezoidal rule.
Time frame: Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available AUCinf data. Participants with unreliable terminal elimination rate constant values were excluded.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose | 149398 h*µg/mL | Geometric Coefficient of Variation 36.2 |
| Rituximab (EU) | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose | 172463 h*µg/mL | Geometric Coefficient of Variation 32.9 |
| Rituximab (US) | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose | 158529 h*µg/mL | Geometric Coefficient of Variation 34.9 |
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.887, 1.0323]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.8204, 0.9542]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.8575, 0.997]
Primary
Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose
Maximum observed concentration following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available Cmax data on day 15.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose | 361 µg/mL | Geometric Coefficient of Variation 23.5 |
| Rituximab (EU) | Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose | 394 µg/mL | Geometric Coefficient of Variation 22 |
| Rituximab (US) | Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose | 372 µg/mL | Geometric Coefficient of Variation 24.7 |
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.9356, 1.0348]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.8912, 0.9848]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.9055, 1.001]
Secondary
Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day)
Area under the serum concentration-time curve from time 0 on day 1 prior to the first infusion of the first dose to 14 days postdose. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUC0-14day was estimated using the linear trapezoidal rule.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available AUC0-14day data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day) | 41445 h*µg/mL | Geometric Coefficient of Variation 28.8 |
| Rituximab (EU) | Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day) | 45161 h*µg/mL | Geometric Coefficient of Variation 24.7 |
| Rituximab (US) | Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day) | 43291 h*µg/mL | Geometric Coefficient of Variation 29.6 |
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.9174, 1.0318]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.8863, 0.9958]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.9104, 1.024]
Secondary
Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk)
Area under the serum concentration-time curve from time 0 on day 1 prior to the first infusion of the first dose to week 12. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUC0-12wk was estimated using the linear trapezoidal rule.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hour postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available AUC0-12wk data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk) | 146369 h*µg/mL | Geometric Coefficient of Variation 34.3 |
| Rituximab (EU) | Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk) | 166995 h*µg/mL | Geometric Coefficient of Variation 30.5 |
| Rituximab (US) | Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk) | 155240 h*µg/mL | Geometric Coefficient of Variation 33.7 |
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance (ANCOVA) model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.895, 1.0303]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an analysis of covariance ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.8363, 0.9616]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.8707, 1.0016]
Secondary
AUC0-12 wk/AUCinf
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | AUC0-12 wk/AUCinf | 0.97 ratio | Geometric Coefficient of Variation 3 |
| Rituximab (EU) | AUC0-12 wk/AUCinf | 0.96 ratio | Geometric Coefficient of Variation 4 |
| Rituximab (US) | AUC0-12 wk/AUCinf | 0.97 ratio | Geometric Coefficient of Variation 3 |
Secondary
Change From Baseline in Disease Activity Score 28-CRP at Week 24
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count * 28 swollen joint count * C-reactive protein (CRP) * Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and Week 24
Population: Full analysis set with observed data conducted using a repeated measures analysis in which data from all assessed postbaseline time points were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Change From Baseline in Disease Activity Score 28-CRP at Week 24 | -2.006 units on a scale | Standard Error 0.1313 |
| Rituximab (EU) | Change From Baseline in Disease Activity Score 28-CRP at Week 24 | -2.116 units on a scale | Standard Error 0.1339 |
| Rituximab (US) | Change From Baseline in Disease Activity Score 28-CRP at Week 24 | -1.936 units on a scale | Standard Error 0.1349 |
| Rituximab (US + EU) | Change From Baseline in Disease Activity Score 28-CRP at Week 24 | -2.026 units on a scale | Standard Error 0.1039 |
Comparison: If PK similarity was established between rituximab (US) and rituximab (EU), the 2 rituximab arms were to be combined into a single reference group for the primary assessment of clinical equivalence of DAS28-CRP change from baseline at week 24 using a repeated measures analysis with DAS28-CRP change from baseline as the response and the stratification variables, visit, treatment, treatment-by-visit interaction and baseline DAS28-CRP as predictors, and unstructured covariance matrix in the model.90% CI: [-0.225, 0.264]
90% CI: [-0.353, 0.213]
90% CI: [-0.171, 0.392]
Secondary
Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count * 28 swollen joint count * C-reactive protein (CRP) * Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline and weeks 8, 12, 40, and 48
Population: Full analysis set with observed data
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 798 | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 40 | -2.038 units on a scale | Standard Error 0.144 |
| ABP 798 | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 8 | -1.674 units on a scale | Standard Error 0.1259 |
| ABP 798 | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 48 | -2.243 units on a scale | Standard Error 0.1473 |
| ABP 798 | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 12 | -1.746 units on a scale | Standard Error 0.1302 |
| Rituximab (EU) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 40 | -2.293 units on a scale | Standard Error 0.1494 |
| Rituximab (EU) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 12 | -2.248 units on a scale | Standard Error 0.1357 |
| Rituximab (EU) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 48 | -2.505 units on a scale | Standard Error 0.1553 |
| Rituximab (EU) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 8 | -1.738 units on a scale | Standard Error 0.1335 |
| Rituximab (US) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 48 | -2.323 units on a scale | Standard Error 0.1486 |
| Rituximab (US) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 8 | -1.527 units on a scale | Standard Error 0.133 |
| Rituximab (US) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 12 | -2.016 units on a scale | Standard Error 0.1367 |
| Rituximab (US) | Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48 | Week 40 | -2.198 units on a scale | Standard Error 0.1489 |
Comparison: Analysis of change from baseline at week 8, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-0.203, 0.33]
Comparison: Analysis of change from baseline at week 8, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-0.411, 0.117]
Comparison: Analysis of change from baseline at week 12, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [0.233, 0.772]
Comparison: Analysis of change from baseline at week 12, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [0, 0.539]
Comparison: Analysis of change from baseline at week 40, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-0.04, 0.55]
Comparison: Analysis of change from baseline at week 40, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-0.135, 0.455]
Comparison: Analysis of change from baseline at week 48, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-0.04, 0.564]
Comparison: Analysis of change from baseline at week 48, based on an ANCOVA model adjusted for baseline DAS28-CRP and the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-0.216, 0.376]
Secondary
Clearance (CL)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available CL data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Clearance (CL) | 0.01339 L/h | Geometric Coefficient of Variation 36.22558 |
| Rituximab (EU) | Clearance (CL) | 0.01160 L/h | Geometric Coefficient of Variation 32.94524 |
| Rituximab (US) | Clearance (CL) | 0.01262 L/h | Geometric Coefficient of Variation 34.93316 |
Secondary
Duration of Complete Depletion in CD19+ Cell Count
Duration of CD19+ B-cell complete depletion was defined as the time from the first incidence of complete depletion of CD19+ cell count (CD19+ cell count \< 20 cells/μL) to when the CD19+ cell count first increased to ≥ 20 cells/μL. Participants whose CD19+ cell count did not increase to ≥ 20 cells/μL were censored at the last CD19+ assessment date.
Time frame: CD19+ cell count was assessed at baseline, days 2, 3, weeks 4, 24, and 48
Population: Full analysis set participants who had a CD19+ complete depletion for at least one postdose time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABP 798 | Duration of Complete Depletion in CD19+ Cell Count | NA days |
| Rituximab (EU) | Duration of Complete Depletion in CD19+ Cell Count | NA days |
| Rituximab (US) | Duration of Complete Depletion in CD19+ Cell Count | NA days |
Secondary
Hybrid ACR
The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Investigator's Global Assessment of Disease Activity, disability index of the HAQ, and CRP) was calculated (a positive change indicates improvement, and the maximum worst change is limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).
Time frame: Baseline and weeks 8, 12, 24, 40, and 48
Population: Full analysis set with observed data
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 798 | Hybrid ACR | Week 8 | 32.631 percent improvement | Standard Error 2.7287 |
| ABP 798 | Hybrid ACR | Week 12 | 36.604 percent improvement | Standard Error 2.891 |
| ABP 798 | Hybrid ACR | Week 24 | 39.269 percent improvement | Standard Error 3.166 |
| ABP 798 | Hybrid ACR | Week 40 | 41.042 percent improvement | Standard Error 3.1508 |
| ABP 798 | Hybrid ACR | Week 48 | 41.917 percent improvement | Standard Error 3.3878 |
| Rituximab (EU) | Hybrid ACR | Week 40 | 43.250 percent improvement | Standard Error 3.1916 |
| Rituximab (EU) | Hybrid ACR | Week 48 | 48.546 percent improvement | Standard Error 3.487 |
| Rituximab (EU) | Hybrid ACR | Week 24 | 40.589 percent improvement | Standard Error 3.1781 |
| Rituximab (EU) | Hybrid ACR | Week 8 | 34.630 percent improvement | Standard Error 2.8058 |
| Rituximab (EU) | Hybrid ACR | Week 12 | 44.828 percent improvement | Standard Error 2.9412 |
| Rituximab (US) | Hybrid ACR | Week 8 | 32.086 percent improvement | Standard Error 2.8628 |
| Rituximab (US) | Hybrid ACR | Week 12 | 38.664 percent improvement | Standard Error 3.036 |
| Rituximab (US) | Hybrid ACR | Week 40 | 41.078 percent improvement | Standard Error 3.2459 |
| Rituximab (US) | Hybrid ACR | Week 24 | 38.539 percent improvement | Standard Error 3.2436 |
| Rituximab (US) | Hybrid ACR | Week 48 | 45.013 percent improvement | Standard Error 3.3942 |
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-7.673, 3.675]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 8, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-5.185, 6.274]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-14.102, -2.346]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 12, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-8.052, 3.933]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-7.62, 4.979]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 24, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-5.691, 7.15]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-8.562, 1.417]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 40, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-6.497, 6.424]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-13.455, 0.197]
Comparison: Analysis of the LS mean difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 48, based on an ANCOVA model adjusted for the stratification variables geographic region, seropositivity, and number of prior biologic therapies used for RA.90% CI: [-9.883, 3.691]
Secondary
Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available Clast data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast) | 5.95 µg/mL | Geometric Coefficient of Variation 154 |
| Rituximab (EU) | Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast) | 8.52 µg/mL | Geometric Coefficient of Variation 145 |
| Rituximab (US) | Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast) | 6.76 µg/mL | Geometric Coefficient of Variation 143 |
Secondary
Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose | 298 µg/mL | Geometric Coefficient of Variation 26.1 |
| Rituximab (EU) | Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose | 321 µg/mL | Geometric Coefficient of Variation 21.2 |
| Rituximab (US) | Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose | 304 µg/mL | Geometric Coefficient of Variation 25.5 |
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.9461, 1.0448]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.9021, 0.9953]
Comparison: The geometric mean ratio (GMR) and confidence interval (CI) was estimated from an ANCOVA model adjusted for weight and geographic region. The GMR was obtained by exponentiating the difference of the means on the natural log scale. The CI was obtained by exponentiating the CI for the difference between the means on the log scale.90% CI: [0.907, 1.0015]
Secondary
Mean Residence Time (MRT)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available MRT data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Mean Residence Time (MRT) | 549 hours | Geometric Coefficient of Variation 26.7 |
| Rituximab (EU) | Mean Residence Time (MRT) | 592 hours | Geometric Coefficient of Variation 26.5 |
| Rituximab (US) | Mean Residence Time (MRT) | 557 hours | Geometric Coefficient of Variation 26.8 |
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: Day 1 through the end of study (48 weeks).
Population: Participants with a binding negative or no result at baseline and an available postbaseline result
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABP 798 | Number of Participants Who Developed Anti-drug Antibodies | Binding antibody positive | 14 Participants |
| ABP 798 | Number of Participants Who Developed Anti-drug Antibodies | Neutralizing antibody positive | 8 Participants |
| Rituximab (EU) | Number of Participants Who Developed Anti-drug Antibodies | Binding antibody positive | 13 Participants |
| Rituximab (EU) | Number of Participants Who Developed Anti-drug Antibodies | Neutralizing antibody positive | 4 Participants |
| Rituximab (US) | Number of Participants Who Developed Anti-drug Antibodies | Binding antibody positive | 20 Participants |
| Rituximab (US) | Number of Participants Who Developed Anti-drug Antibodies | Neutralizing antibody positive | 10 Participants |
Secondary
Number of Participants With Adverse Events After the First Dose
Adverse events (AEs) were graded by the investigator according to National Cancer Institute 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 AE, and Grade 5 = death due to AE. A serious AE (SAE) was defined as an AE that met at least 1 of the following serious criteria: * fatal * life-threatening * required inpatient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. The adverse events of interest prespecified for this study included infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, hypogammaglobulinemia, severe mucocutaneous reactions, and gastrointestinal perforation.
Time frame: From day 1 until the first infusion of the second dose (week 24)
Population: All randomized participants who received at least 1 infusion of study drug (safety analysis set)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any AE leading to discontinuation of drug/study | 3 Participants |
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any adverse event | 52 Participants |
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any adverse event of interest | 19 Participants |
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any serious adverse event | 4 Participants |
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any fatal adverse event | 0 Participants |
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any grade ≥ 3 adverse event | 4 Participants |
| ABP 798 | Number of Participants With Adverse Events After the First Dose | Any AE leading to infusion delayed/ not given | 6 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any adverse event of interest | 11 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any serious adverse event | 5 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any AE leading to discontinuation of drug/study | 1 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any AE leading to infusion delayed/ not given | 6 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any adverse event | 44 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any grade ≥ 3 adverse event | 6 Participants |
| Rituximab (EU) | Number of Participants With Adverse Events After the First Dose | Any fatal adverse event | 0 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any adverse event | 44 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any AE leading to discontinuation of drug/study | 4 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any fatal adverse event | 0 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any grade ≥ 3 adverse event | 4 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any adverse event of interest | 18 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any AE leading to infusion delayed/ not given | 7 Participants |
| Rituximab (US) | Number of Participants With Adverse Events After the First Dose | Any serious adverse event | 5 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Findings
Clinically significant clinical laboratory findings were defined as laboratory results that were ≥ Grade 3, based on the CTCAE version 4.03.
Time frame: Day 1 through the end of study (48 weeks).
Population: All randomized participants who received at least 1 infusion of study drug (safety analysis set)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABP 798 | Number of Participants With Clinically Significant Laboratory Findings | Lymphocytes - decrease | 64 Participants |
| ABP 798 | Number of Participants With Clinically Significant Laboratory Findings | Gamma glutamyl transferase - increase | 5 Participants |
| ABP 798 | Number of Participants With Clinically Significant Laboratory Findings | Hemoglobin - decrease (anemia) | 0 Participants |
| ABP 798 | Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase - increase | 1 Participants |
| ABP 798 | Number of Participants With Clinically Significant Laboratory Findings | Potassium - increase (hyperkalemia) | 0 Participants |
| Rituximab (EU) | Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase - increase | 0 Participants |
| Rituximab (EU) | Number of Participants With Clinically Significant Laboratory Findings | Gamma glutamyl transferase - increase | 0 Participants |
| Rituximab (EU) | Number of Participants With Clinically Significant Laboratory Findings | Potassium - increase (hyperkalemia) | 2 Participants |
| Rituximab (EU) | Number of Participants With Clinically Significant Laboratory Findings | Lymphocytes - decrease | 54 Participants |
| Rituximab (EU) | Number of Participants With Clinically Significant Laboratory Findings | Hemoglobin - decrease (anemia) | 0 Participants |
| Rituximab (US) | Number of Participants With Clinically Significant Laboratory Findings | Potassium - increase (hyperkalemia) | 1 Participants |
| Rituximab (US) | Number of Participants With Clinically Significant Laboratory Findings | Hemoglobin - decrease (anemia) | 1 Participants |
| Rituximab (US) | Number of Participants With Clinically Significant Laboratory Findings | Lymphocytes - decrease | 52 Participants |
| Rituximab (US) | Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase - increase | 0 Participants |
| Rituximab (US) | Number of Participants With Clinically Significant Laboratory Findings | Gamma glutamyl transferase - increase | 2 Participants |
Secondary
Percentage of Participants With an ACR20 Response
A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global health assessment (measured on a 100 mm VAS); * Investigator's global health assessment (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-reactive protein concentration.
Time frame: Baseline and Weeks 8, 12, 24, 40, and 48
Population: Full analysis set with observed data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 798 | Percentage of Participants With an ACR20 Response | Week 40 | 68.8 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR20 Response | Week 12 | 67.6 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR20 Response | Week 48 | 63.2 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR20 Response | Week 8 | 56.4 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR20 Response | Week 24 | 70.7 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR20 Response | Week 8 | 60.0 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR20 Response | Week 40 | 73.7 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR20 Response | Week 24 | 66.7 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR20 Response | Week 48 | 79.8 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR20 Response | Week 12 | 73.3 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR20 Response | Week 48 | 75.0 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR20 Response | Week 12 | 63.3 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR20 Response | Week 24 | 64.2 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR20 Response | Week 40 | 68.1 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR20 Response | Week 8 | 54.6 percentage of participants |
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7696, 1.1332]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.8743, 1.1671]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1495, 0.0775]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.8436, 1.2801]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.091, 0.1402]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7573, 1.0179]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1834, 0.0247]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.877, 1.2394]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0758, 0.1454]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0835, 0.1234]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.9244, 1.2601]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0493, 0.1615]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7759, 1.0091]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1789, 0.0237]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.8585, 1.1605]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1038, 0.1054]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.6722, 0.9196]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.3066, -0.0941]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7587, 1.0215]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.2066, -0.0007]
Secondary
Percentage of Participants With an ACR50 Response
A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global health assessment (measured on a 100 mm VAS); * Investigator's global health assessment (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-reactive protein concentration.
Time frame: Baseline and Weeks 8, 12, 24, 40, and 48
Population: Full analysis set with observed data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 798 | Percentage of Participants With an ACR50 Response | Week 40 | 48.9 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR50 Response | Week 24 | 39.8 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR50 Response | Week 8 | 26.7 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR50 Response | Week 12 | 36.3 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR50 Response | Week 48 | 51.2 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR50 Response | Week 24 | 39.2 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR50 Response | Week 8 | 29.3 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR50 Response | Week 12 | 47.5 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR50 Response | Week 40 | 57.9 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR50 Response | Week 48 | 58.3 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR50 Response | Week 48 | 48.9 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR50 Response | Week 40 | 45.7 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR50 Response | Week 8 | 24.7 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR50 Response | Week 24 | 38.5 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR50 Response | Week 12 | 32.7 percentage of participants |
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.64, 1.3388]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1209, 0.0847]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7328, 1.6119]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0803, 0.1205]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.5387, 0.9346]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.2231, 0.0013]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7829, 1.5127]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0626, 0.1508]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7273, 1.2705]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1081, 0.1122]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.756, 1.3305]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1056, 0.1135]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.6797, 1.0316]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.2029, 0.0302]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.878, 1.4264]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0827, 0.1402]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.6807, 1.0307]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.2014, 0.0452]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.8351, 1.3321]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1021, 0.1303]
Secondary
Percentage of Participants With an ACR70 Response
A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: * Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global health assessment (measured on a 100 mm VAS); * Investigator's global health assessment (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-reactive protein concentration.
Time frame: Baseline and Weeks 8, 12, 24, 40, and 48
Population: Full analysis set with observed data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABP 798 | Percentage of Participants With an ACR70 Response | Week 48 | 28.7 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR70 Response | Week 8 | 6.9 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR70 Response | Week 24 | 19.2 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR70 Response | Week 12 | 12.9 percentage of participants |
| ABP 798 | Percentage of Participants With an ACR70 Response | Week 40 | 27.7 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR70 Response | Week 12 | 19.8 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR70 Response | Week 48 | 39.3 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR70 Response | Week 40 | 27.7 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR70 Response | Week 8 | 12.0 percentage of participants |
| Rituximab (EU) | Percentage of Participants With an ACR70 Response | Week 24 | 19.6 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR70 Response | Week 48 | 24.7 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR70 Response | Week 8 | 9.3 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR70 Response | Week 12 | 16.3 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR70 Response | Week 40 | 22.8 percentage of participants |
| Rituximab (US) | Percentage of Participants With an ACR70 Response | Week 24 | 16.7 percentage of participants |
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.2818, 1.2462]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1285, 0.0136]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.3383, 1.6519]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 8, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0962, 0.0308]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.3704, 1.0872]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.1448, 0.031]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.445, 1.3874]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 12, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-1237, 0.0403]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.5772, 1.4838]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.078, 0.1092]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.6722, 1.8398]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 24, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.063, 0.1119]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.6675, 1.4384]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0707, 0.1456]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7833, 1.787]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 40, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0297, 0.1802]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.493, 1.0017]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[EU\]/Rituximab \[EU\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.211, 0.0294]
Comparison: Risk ratio (ABP 798/ABP 798 versus Rituximab \[US\]/ABP 798\]) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [0.7601, 1.7246]
Comparison: Risk difference (ABP 798/ABP 798 - Rituximab \[US\]/ABP 798) at week 48, based on a generalized linear model adjusted for the stratification factors geographic region, seropositivity, and number of prior biologic therapies used for RA as covariates.90% CI: [-0.0804, 0.1357]
Secondary
Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3
Complete depletion of cluster of differentiation (CD) 19 positive cells was defined as a CD19+ cell count \< 20 cell/μL (0.02 x 10⁹ cell/L).
Time frame: Day 3
Population: Full analysis set participants with a day 3 CD19+ cell count; participants with missing CD19+ cell counts at baseline or with CD19+ cell count \< 20 cell/μL at baseline were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 798 | Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3 | 94.8 percentage of participants |
| Rituximab (EU) | Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3 | 96.9 percentage of participants |
| Rituximab (US) | Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3 | 92.8 percentage of participants |
90% CI: [-0.1083, 0.0593]
90% CI: [-0.061, 0.0984]
Secondary
Percent of AUC Extrapolation (AUC%Extrap)
Percent of AUC extrapolated to infinity in AUCinf. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available AUC%extrap data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Percent of AUC Extrapolation (AUC%Extrap) | 1.91 percent extrapolation | Geometric Coefficient of Variation 161 |
| Rituximab (EU) | Percent of AUC Extrapolation (AUC%Extrap) | 2.62 percent extrapolation | Geometric Coefficient of Variation 146 |
| Rituximab (US) | Percent of AUC Extrapolation (AUC%Extrap) | 2.06 percent extrapolation | Geometric Coefficient of Variation 148 |
Secondary
Terminal Elimination Half-life (t1/2)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available T1/2 data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Terminal Elimination Half-life (t1/2) | 335.62 hours | Geometric Coefficient of Variation 38 |
| Rituximab (EU) | Terminal Elimination Half-life (t1/2) | 375.26 hours | Geometric Coefficient of Variation 32 |
| Rituximab (US) | Terminal Elimination Half-life (t1/2) | 334.57 hours | Geometric Coefficient of Variation 40 |
Secondary
Terminal Elimination Rate Constant (λz)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57 and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available λz data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ABP 798 | Terminal Elimination Rate Constant (λz) | 0.00205 1/h | Geometric Coefficient of Variation 38.61018 |
| Rituximab (EU) | Terminal Elimination Rate Constant (λz) | 0.00187 1/h | Geometric Coefficient of Variation 33.44044 |
| Rituximab (US) | Terminal Elimination Rate Constant (λz) | 0.00205 1/h | Geometric Coefficient of Variation 40.15779 |
Secondary
Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Time frame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Population: The pharmacokinetic (PK) parameter analysis set (randomized participants who received the full protocol-specified infusion on day 1 and had an evaluable ABP 798 or rituximab serum concentration-time profile) with available Tmax data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ABP 798 | Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | After Second Infusion (Day 15) | 3.57 hours |
| ABP 798 | Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | After First Infusion (Day 1) | 4.50 hours |
| Rituximab (EU) | Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | After Second Infusion (Day 15) | 3.67 hours |
| Rituximab (EU) | Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | After First Infusion (Day 1) | 4.67 hours |
| Rituximab (US) | Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | After First Infusion (Day 1) | 4.68 hours |
| Rituximab (US) | Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose | After Second Infusion (Day 15) | 4.12 hours |