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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Abatacept

Detailed Description

SC=Subcutaneous

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Local Institution
  • Cordoba, Argentina, 5016
    • Local Institution
  • Buenos Aires
    • San Fernando, Buenos Aires, Argentina, 1646
      • Local Institution
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Local Institution
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Local Institution
• Mexico
  • Yucatan, Mexico, 97000
    • Local Institution
• Peru
  • Lima, Peru, 33
    • Local Institution
  • Lima, Peru, LIMA 01
    • Local Institution
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Local Institution
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0122
      • Local Institution
    • Pretoria, Gauteng, South Africa, 0184
      • Local Institution
  • Western Cape
    • George, Western Cape, South Africa, 6529
      • Local Institution
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Rheumatology Associates Of North Alabama, P.C.
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Immunoe Int'L Research Ctrs
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Cru Inc
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Djl Research, Pllc
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Community Research
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: June 27, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (Estimate): July 1, 2013

Study Record Updates

• Last Update Posted (Estimate): November 26, 2015
• Last Update Submitted That Met QC Criteria: October 23, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM101-366