Study to Characterize the Pharmacokinetics of a Single Dose of SC Abatacept 125 mg Using the BD Autoinjector or the Prefilled Syringe

Study Overview
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Brief Summary
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The primary purpose of the protocol is to describe the pharmacokinetics of a single dose of Abatacept 125 mg in Rheumatoid Arthritis patients delivered via the autoinjector device or the approved prefilled syringe.

Detailed Description
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SC=Subcutaneous

Official Title
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Phase Ib, Multicenter, Randomized, Open-Label, Parallel-Group Study to Characterize the Pharmacokinetics of a Single Dose of Abatacept 125 mg Administered Subcutaneously Using the BD Physioject™ Autoinjector or the UltraSafe Passive Needle Guard Prefilled Syringe

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Abatacept


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects ≥18 years of age Diagnosis of Rheumatoid Arthritis confirmed by participant's physician Disease activity under control Key Exclusion Criteria: Change in disease-modifying antirheumatic drug (DMARD) therapy within 3 months of enrollment Exposure to investigational drug within 4 weeks or 5 half lives whichever is longer Current or prior use of Rituximab ≤6 months Current or prior use of the following within 4 weeks or 5 half lives whichever is longer: biologic DMARDS, Tofacitinib, Cyclophosphamide, Mycophenolate Mofetil & d-Penicillamine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Abatacept (autoinjector)<br>Abatacept 125 mg/syringe subcutaneously through autoinjector, one dose in 71 days | Drug: Abatacept<br> <br> * Other names: BMS-188667;|
| Experimental: Arm 2: Abatacept (prefilled syringe)<br>Abatacept 125 mg/syringe subcutaneously with prefilled syringe, one dose in 71 days | Drug: Abatacept<br> <br> * Other names: BMS-188667;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Geometric Mean of Maximum Observed Serum Concentration (Cmax) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (μg/mL). Blood samples for pharmacokinetic (PK) parameters were collected at Day 1 pre-dose at 0 hour (h), 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. | Day 1 to Day 71 | 
| Adjusted Geometric Mean of Area Under the Serum Concentration-time Curve (AUC) From Zero to the Last Time of the Last Quantifiable Concentration (0-T) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using ELISA. AUC (0-T) was measured in μg*h/mL. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. | Day 1 to Day 71 | 
| Adjusted Geometric Mean of Area Under the Serum Concentration-time Curve From Time Zero to Extrapolated to Infinity, AUC (INF), of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 hour (h), 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. AUC (INF) was measured in μg*h/mL | Day 1 to Day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median of Time to Reach Cmax in Serum (Tmax) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. Tmax was measured in hours (h). | Day 1 to Day 71 | 
| Mean of Terminal Phase Elimination Half-life in Serum (T-HALF) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. T-HALF was measured in hours (h). | Day 1 to Day 71 | 
| Geometric Mean of Total Body Clearance (CL/F) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. CL/F was measured in milliliters per hour per kilogram body weight (mL/h/kg). | Day 1 to Day 71 | 
| Geometric Mean of Volume of Distribution (V/F) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population | Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. V/F was measured in liters per kilogram body weight (L/kg) | Day 1 to Day 71 | 
| Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Includes data Day 1 up to 76 days (71 days + 5 day window) post the single dose of study drug. | Day 1 to 76 days post single dose | 
| Number of Participants With Adverse Events of Special Interest | Prospectively identified events of special interest which were a subset of all AEs, and were either SAEs or non-serious AEs, included the following categories: Infections, Autoimmune Disorders, Malignancy, local site reactions, any AE occurring within 24 hours of SC injection. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. | Day 1 to 76 days post single dose | 
| Number of Participants With a Positive Immunogenicity Response Relative to Baseline | Blood samples were screened at baseline, Day 57 and Day 71 for the presence of drug-specific antibodies using Electrochemiluminescence (ECL). A positive immunogenicity response relative to baseline for Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4) and 'possibly immunoglobulin (Ig)', and 'Ig and/or Junction Region', respectively, was defined as: A missing baseline immunogenicity measurement and a positive analytical laboratory reported immunogenicity response post-baseline; A negative baseline immunogenicity response and a positive analytical laboratory reported immunogenicity response post-baseline; A positive baseline immunogenicity response and a positive analytical laboratory reported immunogenicity response post-baseline that has a titer value strictly greater than the baseline titer value. Baseline=Pre-dose value. | Day 57, Day 71 | 
| Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria | Marked abnormality criteria: lower limit of normal (LLN); upper limit of normal (ULN); pretreatment (preRX); cells per microliter (cµ/L); milligram per deciliter (mg/dL); milliequivalent (mEq): Hematology: leukocytes (*10^3 c/µL): <0.75*LLN or >1.25*ULN, or if preRX <LLN, use <0.8*preRX or >ULN, or if preRX>ULN, use >1.2*preRX or <LLN; eosinophils (*10^3 cµ/L): if value >0.750*10^3 c/µL; lymphocytes (*10^3 cµ/L): if value <0.750*10^3 c/µL or if value >7.50*10^3 c/µL. Chemistry: blood urea nitrogen (mg/dL): >2*preRX; creatinine (mg/dL): >1.5*preRX; potassium (mEq/L): <0.9*LLN or >1.1*ULN, or if preRX<LLN, use <0.9*preRX or >ULN, or if preRX>ULN, use 1.1*preRX or <LLN; glucose (mg/dL): <65 mg/dL (low) or >220 mg/dL (high). Urine Blood, urine red blood cell (RBC), urine white blood cell (WBC): if missing PreRX use >= 2, or if Value >= 4, or if preRX = 0 or 0.5 then use >= 2, or if preRX = 1 then use >= 3, or if preRX = 2 or 3 then use >= 4. | Day 1 to 76 days post last dose |