Study to Assess if ABP 798 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis (RA) Compared to Rituximab

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.

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.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Percent of AUC extrapolated to infinity in AUCinf. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.

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.

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.

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.

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.

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.

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).

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 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.

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.

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.

Clinically significant clinical laboratory findings were defined as laboratory results that were ≥ Grade 3, based on the CTCAE version 4.03.