Methotrexate - Inadequate Response Device Sub-Study - Clinical Trial for Rheumatoid Arthritis (RA) | NCT01173120

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Abatacept combination product (ACP)

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis (RA)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Abatacept Combination Product (ACP)

Arm Description

Participants from the long-term period of study NCT00559585 who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a pre-filled liquid product device delivering 125 mg abatacept/device (125 mg/mL).

Outcomes

Primary Outcome Measures

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.

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).

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 <LLN, use 0.5*BL/<100,000 mm^3; Leukocytes: <0.75*LLN/ >1.25*ULN, or if BL<LLN, use <0.8*BL/>ULN, or if BL>ULN, use >1.2*BL/<LLN; neutrophils+bands: <1.0*10^3 c/uL; eosinophils: >0.750*10^3 c/uL; basophils: >400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750*10^3 c/uL/ >7.50*10^3 c/uL.

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

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<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN

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<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3

Mean Systolic Blood Pressure (SBP) Over Time in the ACP Device Substudy

Mean Diastolic Blood Pressure (DBP) Over Time in the ACP Device Substudy

Mean Heart Rate Over Time in the ACP Device Substudy

Mean Temperature Over Time in the ACP Device Substudy

Secondary Outcome Measures

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.

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.

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

Full Information

NCT ID

NCT01173120

First Posted

July 28, 2010

Last Updated

January 9, 2012

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01173120

Brief Title

Methotrexate - Inadequate Response Device Sub-Study

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2012

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

February 2010 (Actual)

Study Completion Date

July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis (RA)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Abatacept Combination Product (ACP)

Arm Type

Experimental

Arm Description

Participants from the long-term period of study NCT00559585 who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a pre-filled liquid product device delivering 125 mg abatacept/device (125 mg/mL).

Intervention Type

Device

Intervention Name(s)

Abatacept combination product (ACP)

Other Intervention Name(s)

Orencia, BMS-188667

Intervention Description

Abatacept Solution, Subcutaneous, 125 mg/device, Weekly, 3 months

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

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

Title

Number of Participants With AEs of Special Interest in the ACP Device Substudy

Description

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).

Time Frame

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

Title

Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality in the ACP Device Substudy

Description

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 <LLN, use 0.5*BL/<100,000 mm^3; Leukocytes: <0.75*LLN/ >1.25*ULN, or if BL<LLN, use <0.8*BL/>ULN, or if BL>ULN, use >1.2*BL/<LLN; neutrophils+bands: <1.0*10^3 c/uL; eosinophils: >0.750*10^3 c/uL; basophils: >400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750*10^3 c/uL/ >7.50*10^3 c/uL.

Time Frame