Back to resultsStudy to Assess if ABP 798 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis (RA) Compared to Rituximab
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ABP 798
Rituximab (US)
Rituximab (EU)
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid
Eligibility Criteria
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/Exclusion criteria may apply
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
ABP 798 / ABP 798
Rituximab (US) / ABP 798
Rituximab (EU) / Rituximab (EU)
Arm Description
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.
Participants received rituximab (United States [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.
Participants received rituximab (European Union [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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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 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.
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.
Terminal Elimination Half-life (t1/2)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Terminal Elimination Rate Constant (λz)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Clearance (CL)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
Mean Residence Time (MRT)
Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
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.
AUC0-12 wk/AUCinf
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
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.
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.
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.
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.
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.
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).
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).
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02792699
Brief Title
Study to Assess if ABP 798 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis (RA) Compared to Rituximab
Official Title
A Randomized, Double-blind Study to Compare Pharmacokinetics and Pharmacodynamics, Efficacy and Safety of ABP 798 With Rituximab in Subjects With Moderate to Severe Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 17, 2016 (Actual)
Primary Completion Date
October 8, 2018 (Actual)
Study Completion Date
October 8, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
311 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABP 798 / ABP 798
Arm Type
Experimental
Arm Description
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.
Arm Title
Rituximab (US) / ABP 798
Arm Type
Active Comparator
Arm Description
Participants received rituximab (United States [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.
Arm Title
Rituximab (EU) / Rituximab (EU)
Arm Type
Active Comparator
Arm Description
Participants received rituximab (European Union [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.
Intervention Type
Drug
Intervention Name(s)
ABP 798
Intervention Description
Supplied as a 10 mg/mL liquid concentrate for intravenous (IV) administration.
Intervention Type
Drug
Intervention Name(s)
Rituximab (US)
Other Intervention Name(s)
Rituxan®
Intervention Description
Supplied as a 10 mg/mL liquid concentrate for IV administration.
Intervention Type
Drug
Intervention Name(s)
Rituximab (EU)
Other Intervention Name(s)
MabThera®
Intervention Description
Supplied as a 10 mg/mL liquid concentrate for IV administration.
Primary Outcome Measure Information:
Title
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose
Description
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.
Title
Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose
Description
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.
Secondary Outcome Measure Information:
Title
Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day)
Description
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.
Title
Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk)
Description
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).
Title
Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose
Description
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.
Title
Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose
Description
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).
Title
Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast)
Description
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).
Title
Terminal Elimination Half-life (t1/2)
Description
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).
Title
Terminal Elimination Rate Constant (λz)
Description
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).
Title
Clearance (CL)
Description
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).
Title
Mean Residence Time (MRT)
Description
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).
Title
Percent of AUC Extrapolation (AUC%Extrap)
Description
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).
Title
AUC0-12 wk/AUCinf
Description
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).
Title
Change From Baseline in Disease Activity Score 28-CRP at Week 24
Description
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
Title
Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48
Description
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
Title
Percentage of Participants With an ACR20 Response
Description
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
Title
Percentage of Participants With an ACR50 Response
Description
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
Title
Percentage of Participants With an ACR70 Response
Description
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
Title
Hybrid ACR
Description
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
Title
Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3
Description
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
Title
Duration of Complete Depletion in CD19+ Cell Count
Description
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
Title
Number of Participants With Adverse Events After the First Dose
Description
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)
Title
Number of Participants Who Developed Anti-drug Antibodies
Description
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).
Title
Number of Participants With Clinically Significant Laboratory Findings
Description
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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/Exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35406
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1670
Country
United States
Facility Name
Research Site
City
Thousand Oaks
State/Province
California
ZIP/Postal Code
91360
Country
United States
Facility Name
Research Site
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Research Site
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Research Site
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Facility Name
Research Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32810
Country
United States
Facility Name
Research Site
City
Vero Beach
State/Province
Florida
ZIP/Postal Code
32960
Country
United States
Facility Name
Research Site
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
Facility Name
Research Site
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
Research Site
City
Flowood
State/Province
Mississippi
ZIP/Postal Code
39232
Country
United States
Facility Name
Research Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Research Site
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Research Site
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
Facility Name
Research Site
City
Summerville
State/Province
South Carolina
ZIP/Postal Code
29486
Country
United States
Facility Name
Research Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
Research Site
City
Carrollton
State/Province
Texas
ZIP/Postal Code
75007-1601
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Research Site
City
League City
State/Province
Texas
ZIP/Postal Code
77573
Country
United States
Facility Name
Research Site
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Research Site
City
Plano
State/Province
Texas
ZIP/Postal Code
75024
Country
United States
Facility Name
Research Site
City
Olympia
State/Province
Washington
ZIP/Postal Code
98502
Country
United States
Facility Name
Research Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Research Site
City
Sofia
State/Province
Sofiya
ZIP/Postal Code
1233
Country
Bulgaria
Facility Name
Research Site
City
Sofia
State/Province
Sofiya
ZIP/Postal Code
1612
Country
Bulgaria
Facility Name
Research Site
City
Plovdiv
ZIP/Postal Code
4003
Country
Bulgaria
Facility Name
Research Site
City
Tallinn
State/Province
Harjuma
ZIP/Postal Code
10117
Country
Estonia
Facility Name
Research Site
City
Tartu
ZIP/Postal Code
50106
Country
Estonia
Facility Name
Research Site
City
Bad Nauheim
State/Province
Hessen
ZIP/Postal Code
61231
Country
Germany
Facility Name
Research Site
City
Magdeburg
State/Province
Sachsen-anhalt
ZIP/Postal Code
39120
Country
Germany
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Research Site
City
Gyula
State/Province
Bekes
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Research Site
City
Szentes
State/Province
Csongrad
ZIP/Postal Code
6600
Country
Hungary
Facility Name
Research Site
City
Budapest
State/Province
Pest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Research Site
City
Szombathely
State/Province
VAS
ZIP/Postal Code
9700
Country
Hungary
Facility Name
Research Site
City
Veszprém
State/Province
Veszprem
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Research Site
City
Wrocław
State/Province
Dolnoslaskie
ZIP/Postal Code
50-556
Country
Poland
Facility Name
Research Site
City
Bydgoszcz
State/Province
Kujawsko-pomorskie
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Research Site
City
Łódź
State/Province
Lodzkie
ZIP/Postal Code
91-363
Country
Poland
Facility Name
Research Site
City
Lublin
State/Province
Lubelskie
ZIP/Postal Code
20-582
Country
Poland
Facility Name
Research Site
City
Kraków
State/Province
Malopolskie
ZIP/Postal Code
30-033
Country
Poland
Facility Name
Research Site
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-637
Country
Poland
Facility Name
Research Site
City
Stalowa Wola
State/Province
Podkarpackie
ZIP/Postal Code
37-450
Country
Poland
Facility Name
Research Site
City
Białystok
State/Province
Podlaskie
ZIP/Postal Code
15-297
Country
Poland
Facility Name
Research Site
City
Gdańsk
State/Province
Pomorskie
ZIP/Postal Code
80-382
Country
Poland
Facility Name
Research Site
City
Katowice
State/Province
Slaskie
ZIP/Postal Code
40-282
Country
Poland
Facility Name
Research Site
City
Elbląg
State/Province
Warminsko-mazurskie
ZIP/Postal Code
82-300
Country
Poland
Facility Name
Research Site
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
60-218
Country
Poland
Facility Name
Research Site
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
60-529
Country
Poland
Facility Name
Research Site
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
61-397
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
IPD Sharing Time Frame
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
IPD Sharing Access Criteria
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
IPD Sharing URL
https://www.amgen.com/datasharing
Citations:
PubMed Identifier
32627420
Citation
Burmester G, Chien D, Chow V, Gessner M, Pan J, Cohen S. A Randomized, Double-Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis. Clin Pharmacol Drug Dev. 2020 Nov;9(8):1003-1014. doi: 10.1002/cpdd.845. Epub 2020 Jul 5.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Study to Assess if ABP 798 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis (RA) Compared to Rituximab
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