Methotrexate-Inadequate Response Autoinjector Device Sub Study (MTX-IR)

Substudy-A Phase IIIB Multicenter, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Abatacept Administered Subcutaneously and Intravenously in Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate

The purpose of this study is to implement a substudy in approximately 120 rheumatoid arthritis (RA) subjects to compare the steady-state serum trough concentration (Cminss), Cmax and area under the curve (AUC) during the dosing interval (TAU) of subcutaneous (SC) Abatacept injection of 125 mg via the autoinjector and via the BD Hypak™ Physiolis prefilled syringe.

Study Overview

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

Detailed Description

Study Classification:

• Safety: show if the drug is safe under conditions of proposed use
• Efficacy: measure of an intervention's influence on a disease or health condition
• Safety/Efficacy
• Pharmacokinetics: the action of a drug in the body over a period of time including the process of absorption, distribution and localization in tissue, biotransformation, and excretion of the compound.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

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

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects who have been treated in the long term (LT) with open-label SC Abatacept for at least 3 months
• Must continue to meet inclusion criteria specified in main IM101-174 Study Protocol

Exclusion Criteria:

• Participation in previous device substudy (implemented by Amendment 10)
• Must continue to meet exclusion criteria specified in main IM101-174 Study Protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abatacept (Autoinjector and Prefilled Syringe); Abatacept (prefilled syringe) 125 mg/device solution subcutaneously weekly for 3 months Abatacept (autoinjector) 125 mg/device solution subcutaneously weekly for 1 month	Drug: Abatacept; Other Names: Orencia; BMS-188667

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Analysis: Adjusted Geometric Mean Observed Serum Trough Concentration at Steady State (Cminss) of Abatacept Using a Prefilled Syringe (Measured on Day 29) and Using an Autoinjector (Measured on Day 113)	Abatacept SC was self-administered with a prefilled syringe every 7 days for the first 4 weeks until Day 29; Blood samples for PK were taken pre-dose (0 hour) on Days 29 and 113. Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Steady-state trough observed concentration in serum (Cminss) was measured in micrograms/milliliter (μg/mL). Adjusted geometric mean and 90% confidence interval (CI) are presented.	Day 29, Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Analysis: Geometric Mean of Maximum Observed Serum Concentration (Cmax) of Abatacept During the Sampling Period Between Substudy Days 22 and 29 for the Prefilled Syringe and Between Substudy Days 106 and Day 113 for the Autoinjector	Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken on Days 1 and 22 at 0 hour (predose), Day 24 at 48 hour (h) post dose, Day 25 at 72 h post dose, Day 26 at 96 h post dose and Day 29 at 0 h (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy; Blood samples for PK were taken on Day 108 at 48 h post dose, Day 109 at 72 h post dose, Day 110 at 96 h post dose and at Day 113 0h (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. Cmax was measured in μg/mL.	Days 22, 24, 25, 26, 29 (prefilled syringe); Days 106, 108, 109, 110, 113 (autoinjector)
PK Analysis: Median Time to Achieve Cmax (Tmax) During the Sampling Period Between Days 22 and 29 for the Prefilled Syringe and Between Days 106 and Day 113 for the Autoinjector	Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken on Days 1 and 22 at 0 hour (predose), Day 24 at 48 hour (h) post dose, Day 25 at 72 h post dose, Day 26 at 96 h post dose and Day 29 at 0 h (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy; Blood samples for PK were taken on Day 108 at 48 h post dose, Day 109 at 72 h post dose, Day 110 at 96 h post dose and at Day 113 0h (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. Tmax was measured in hours (h).	Days 22, 24, 25, 26, 29 (prefilled syringe); Days 106, 108, 109, 110,113 (autoinjector)
Geometric Mean of Area Under Serum Concentration-time (AUC) During a Dosing Interval (TAU) of Abatacept During the Sampling Period Between Days 22 and 29 for the Prefilled Syringe and Between Days 106 and Day 113 for the Autoinjector	Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken on Days 1 and 22 at 0 hour (predose), Day 24 at 48 hour (h) post dose, Day 25 at 72 h post dose, Day 26 at 96 h post dose and Day 29 at 0 h (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy; Blood samples for PK were taken on Day 106 at 0 h (predose), Day 108 at 48 h post dose, Day 109 at 72 h post dose, Day 110 at 96 h post dose and at Day 113 0h (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. AUC(TAU) where TAU = 168 hours was calculated in µg*h/mL	Days 22, 24, 25, 26,29 (prefilled syringe); Days 106, 108, 109, 110, 113 (autoinjector)
Geometric Mean of Trough Serum Concentration (Cmin) Over Time and During the Switch From Prefilled Syringe to Autoinjector on Days 22, 29, 57, 85, 106, and 113	Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken at 0 hour (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy. Blood samples for PK were taken at 0 hour (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. Steady-state trough observed concentration in serum (Cminss) was measured in micrograms/milliliter (μg/mL).	Days 22, 29, 57, 85, 106, and 113
Number of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) on Day 29 and Day 113.	Serum samples for immunogenicity were evaluated for presence of anti-abatacept antibodies using a validated bridging ECL on Day 29 and Day 113. The ECL assay differentiated between 2 antibody specificities: the immunoglobulin (Ig) G and/or junction region and cytotoxic leukocyte antigen 4 (CTLA4) and possibly Ig. A positive immunogenicity response relative to baseline 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.	Days 29 and 113

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 5, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: June 30, 2015
• Last Verified: June 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: IM101-174 Substudy-2; 2007-005434-37 (EudraCT Number)