This was a randomized, double-blind, active-controlled, multiple-dose, clinical similarity study to evaluate the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability and immunogenicity of ABP 798 compared with rituximab in subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden. Subjects were randomized in a 1:1 ratio to receive a 375 mg/m\^2 intravenous infusion of either ABP 798 or rituximab once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
256
ABP 798 was supplied as a sterile, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.
Rituximab was procured from commercial supplies in the US and was supplied as a sterile, clear, colorless, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100-mg/10 mL or 500-mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.
Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease
Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria \[Cheson et al, 1999\]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by \>75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; \>=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.
Time frame: Post treatment up to Week 28
Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease
Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria \[Cheson et al, 1999\]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by \>75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; \>=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.
Time frame: Week 12
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Research Site
Encinitas, California, United States
Research Site
Mount Sterling, Kentucky, United States
Research Site
Billings, Montana, United States
Research Site
Zanesville, Ohio, United States
Research Site
Roanoke, Virginia, United States
Research Site
Gosford, New South Wales, Australia
Research Site
Frankston, Victoria, Australia
Research Site
Perth, Western Australia, Australia
Research Site
Plovdiv, Bulgaria
Research Site
Stara Zagora, Bulgaria
...and 88 more locations
Pharmacokinetic Serum Concentrations by Visit
Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations \>0.
Time frame: Weeks 2, 3, 4, 12 and 20
Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8
Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts \< 20 cell/μL (0.02 \* 10\^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count \< 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.
Time frame: Baseline (Day 1), Study Day 8
Total Immunoglobulin G (IgG) Results by Visit
Samples were analyzed by a central lab.
Time frame: Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Total Immunoglobulin M (IgM) Results by Visit
Samples were analyzed by a central lab.
Time frame: Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Participants With Treatment-Emergent Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. IP = investigational product
Time frame: Day 1 (post treatment) to Week 28
Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs)
The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome. Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date.
Time frame: Day 1 (post treatment) to Week 28
Number of Participants Who Developed Anti-drug Antibodies
Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay). Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point.
Time frame: Baseline (Day 1), Weeks 12, 20 and 28
Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease
PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.
Time frame: Day 1 up to Week 28
Percentage of Participants Who Survived -- Overall Survival (OS)
Percentage of participants who were alive at the end of the study.
Time frame: Day 1 up to Week 28