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

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ClinicalTrials.gov Identifier: NCT01844895
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : July 1, 2015
Last Update Posted : July 23, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE April 5, 2013
First Posted Date  ICMJE May 3, 2013
Results First Submitted Date  ICMJE June 5, 2015
Results First Posted Date  ICMJE July 1, 2015
Last Update Posted Date July 23, 2015
Study Start Date  ICMJE April 2013
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2015)
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) [ Time Frame: Day 29, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2013)
  • Cminss (μg/mL) trough serum concentration of Abatacept at steady-state on substudy Day 29 (BD Hypak™ Physiolis prefilled syringe) [ Time Frame: Day 29 (BD Hypak™ Physiolis prefilled syringe) ]
  • Cminss (μg/mL) trough serum concentration of Abatacept at steady-state on substudy Day 113 (autoinjector) [ Time Frame: Day 113 (autoinjector) ]
Change History Complete list of historical versions of study NCT01844895 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2015)
  • 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 [ Time Frame: Days 22, 24, 25, 26, 29 (prefilled syringe); Days 106, 108, 109, 110, 113 (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.
  • 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 [ Time Frame: Days 22, 24, 25, 26, 29 (prefilled syringe); Days 106, 108, 109, 110,113 (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).
  • 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 [ Time Frame: Days 22, 24, 25, 26,29 (prefilled syringe); Days 106, 108, 109, 110, 113 (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
  • 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 [ Time Frame: 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).
  • Number of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) on Day 29 and Day 113. [ Time Frame: Days 29 and 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2013)
  • Maximum observed serum concentration [Cmax (μg/mL)] of Abatacept during the sampling period between substudy Days 22 and 29 for the BD Hypak™ Physiolis prefilled syringe [ Time Frame: Days 22, 24, 25, 26 and 29 (BD Hypak™ Physiolis prefilled syringe) ]
  • Maximum observed serum concentration [Cmax (μg/mL)] of Abatacept during the sampling period between substudy Days 106 and Day 113 for the autoinjector [ Time Frame: Days 106, 108, 109, 110 and 113 (autoinjector) ]
  • Time to achieve Cmax [Tmax (days)] during the sampling period between substudy Days 22 and 29 for the BD Hypak™ Physiolis prefilled syringe [ Time Frame: Days 22, 24, 25, 26 and 29 (BD Hypak™ Physiolis prefilled syringe) ]
  • Time to achieve Cmax [Tmax (days)] during the sampling period between substudy Days 106 and 113 for the autoinjector [ Time Frame: Days 106, 108, 109, 110 and 113 (autoinjector) ]
  • Area under serum concentration-time [AUC(TAU)] profile over dosing interval during sampling period between substudy Days 22 and 29 for BD Hypak™ Physiolis prefilled syringe [ Time Frame: Days 22, 24, 25, 26 and 29 (BD Hypak™ Physiolis prefilled syringe) ]
  • Area under serum concentration-time [AUC(TAU)] profile over dosing interval during sampling period between substudy Days 106 and 113 for autoinjector [ Time Frame: Days 106, 108, 109, 110 and 113 (autoinjector) ]
  • Safety and tolerability evaluation are based on clinical adverse events (AEs) [ Time Frame: Up to Day 113 ]
    Frequency distribution of all AEs will be generated
  • Immunogenicity assessment based on analysis of anti-Abatacept antibodies in serum [ Time Frame: Days 29 and 113 ]
    Incidence of a positive response during the substudy will be summarized as well as by injection device
  • Abatacept systemic exposure over time and during the switch from BD Hypak™ Physiolis prefilled syringe to the autoinjector using trough serum concentration (Cmin) [ Time Frame: Days 1, 22, 29, 57, 85, 106, and 113 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methotrexate-Inadequate Response Autoinjector Device Sub Study
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE Drug: Abatacept
Other Names:
  • Orencia
  • BMS-188667
Study Arms  ICMJE 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

Intervention: Drug: Abatacept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 29, 2013)
120
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01844895
Other Study ID Numbers  ICMJE IM101-174 Substudy-2
2007-005434-37 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP