Methotrexate - Inadequate Response Device Sub-Study

Rheumatoid Arthritis (RA) Clinical Trial

— MTX-IR  

Official title:

Sub-study-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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01173120
• Other study ID #: IM101-174 (Sub study)
• Secondary ID: 2007-005434-37
• Status: Completed
• Phase: Phase 3
• First received: July 28, 2010
• Last updated: January 9, 2012
• Start date: November 2009
• Est. completion date: July 2010

Study information

• Verified date: January 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and acceptability of a device used in place of traditional syringes for abatacept self-injection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: July 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women, ages = 18

• Participants who are considered methotrexate inadequate responders (MTX-IR)

• 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)

• Participants were to have been enrolled in the main MTX-IR study and been treated with open label abatacept for at least 3 months in the long term period

Exclusion Criteria:

• Participants who failed one or multiple anti-tumor necrosis factor (TNF) therapies

• Participants who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematosus)

• Participants with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)

• Participants with severe chronic or recurrent bacterial infections

• Participants who have received treatment with rituximab

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis (RA)

Intervention

Device:
• Abatacept combination product (ACP)
Abatacept Solution, Subcutaneous, 125 mg/device, Weekly, 3 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation	An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.	ACP substudy Day 1 to last substudy assessment occurring prior to the 1st dose of non-ACP subcutaneous (SC) abatacept, assessed up to 12 months	Yes
Primary	Number of Participants With AEs of Special Interest in the ACP Device Substudy	AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs including all infections, local injection reactions (prespecified), and systemic injection reactions (within 24 hours of dosing).	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 56 days post last ACP dose	Yes
Primary	Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality in the ACP Device Substudy	BL=baseline; LLN lower limit of normal; ULN=upper limit of normal. Marked abnormality criteria: Hemoglobin: >3 g/dL decrease from BL; Hematocrit: <0.75*BL; Erythrocytes: <0.75*BL; Platelets: <0.67*LLN/>1.5*ULN, or if BL	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Number of Participants With Liver Function Laboratories Meeting MA Criteria in the ACP Device Substudy	Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Number of Participants With Electrolyte Laboratories Meeting MA Criteria in the ACP Device Substudy	Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria in the ACP Device Substudy	MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Mean Systolic Blood Pressure (SBP) Over Time in the ACP Device Substudy		ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Mean Diastolic Blood Pressure (DBP) Over Time in the ACP Device Substudy		ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Mean Heart Rate Over Time in the ACP Device Substudy		ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Primary	Mean Temperature Over Time in the ACP Device Substudy		ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.	Yes
Secondary	Minimum Observed Serum Concentration (Cmin) of Abatacept Over Time in the ACP Device Substudy	Trough levels of abatacept were evaluated based upon serum samples. Day 1 pharmacokinetics were based on exposure to the pre-filled syringes and did not reflect abatacept exposure via the ACP device.	Days 1, 29, 57, 85, 169, and 253 of ACP substudy	No
Secondary	Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunosorbant Assay (ELISA) in the ACP Device Substudy	Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 28 days post last ACP dose	Yes
Secondary	Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay in the ACP Device Substudy	An electrochemiluminescence immunoassay screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly immunoglobulin (Ig) category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNCT)category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing. TRT=treatment	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 85 days post last ACP dose	Yes