Phase IIIB Switching From Intravenous to Subcutaneous Study

Phase 3

Completed

Conditions: Arthritis, Rheumatoid

Interventions: Drug: Abatacept

Registration Number: NCT00663702

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this study is to determine whether switching to subcutaneous administration of abatacept will be safe in participants with rheumatoid arthritis who previously received long-term therapy with intravenous abatacept

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 123

Inclusion Criteria

Recruitment from 2 Bristol-Myers Squibb (BMS) studies (BMS IM101-029 [NCT00048581] and BMS IM101-102 [NCT00048568]).
Completion of final quarterly dosing visit in NCT00048581 or NCT00048568 as follows: US and Canadian participants: Day 1821 visit; Taiwanese participants: Day 1905 visit; Mexican participants: Day 1989 visit.
Agreement to participate in BMS IM101-185 (NCT00663702) on final quarterly dosing visit in NCT00048581 or NCT00048568 study as follows: US and Canadian participants: Day 1821 visit; Taiwanese participants: Day 1905 visit; Mexican participants: Day 1989 visit.
At the time of completion of the NCT00048581 or NCT00048568 protocol, participant did not meet any criteria requiring their discontinuation.
Drug stabilization requirements: Participants who received concomitant medications (disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal anti-inflammatory drugs) at the time of their last quarterly dosing visit for NCT00048581 or NCT00048568 were required to maintain stable dose levels from the time they signed consent until the end of the first 3 months (Day 85) of the current study.
Willingness to self-inject study medication (abatacept) or allow a caregiver to inject study medication.
Willingness to adhere to study visit schedule and comply with other protocol requirements.
Male or female (not nursing or pregnant)genders, at least 18 years of age. Women of childbearing potential (WOCBP) must have been practicing adequate contraceptive measures during the study and for up to 10 weeks after the last infusion of study medication in such a manner that the risk of pregnancy was minimized. WOCBP must have had a negative serum or urine pregnancy test result (minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 48 hours prior to the start of study medication.

Exclusion Criteria

The following treatment or therapies should not be started on or after the final quarterly dosing visit from the NCT00048581 or NCT00048568 study: Any biologic; immunoabsorption columns (such as Prosorba columns); mycophenolate mofetil; cyclosporin A or other calcineurin inhibitors; D-penicillamine; any live vaccines within 3 months of Day 1 or scheduled to receive a live vaccine during the course of the study
Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, or a concomitant medical condition that, in the opinion of the Investigator, might have placed the participation at unacceptable risk for study participation
Any clinical laboratory test result that was considered to be abnormal or not within acceptable limits on the final quarterly dosing visit of NCT00048581 or NCT00048568. Screening laboratory test results for NCT00663702 were based on the Day 1821 visit of NCT00048581 or NCT00048568 for participants enrolled at sites in the US or Canada and on the Day 1989 visit of NCT00048568 for participants enrolled at sites in Mexico.
Imprisonment or involuntarily incarceration for treatment of either a psychiatric or physical (eg, infectious disease) illness
Impairment, incapacitation, inability to complete study-related assessments, or illiteracy.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Abatacept	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85	Day 1 (Baseline) through Day 85	An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators. Systemic injection reaction occurring ≤ 24 hours after dosing.
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators.
Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Hemoglobin (g/dL) \>3 decrease from preRx. Hematocrit (%)\<0.75\preRx. Erythrocytes (\10\^6 c/uL) \<0.75\preRx. Platelet count (\10\^9 c/L) \<0.67\LLN or 1.5\ULN or, if preRx\<LLN, use \<0.5\preRx and \<100,000 mm\^3. Leukocytes (\10\^3 c/uL) \<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 \>0.750\10\^3 c/uL. Lymphocytes \<0.750\10\^3 c/uL or \>7.50\*10\^3 c/uL.
Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (U/L) \>2\ULN or if preRx\>ULN, use 3\preRx. Alanine aminotransferase (U/L)\>3\ULN or if preRx\>ULN, use \>4\preRx. G-glutamyl transferase (U/L)\>2\ULN or if preRx\>ULN, use \>3\preRx. Blood urea nitrogen (mg/dL)\>2\preRx. Creatinine (mg/dL)\>1.5\preRx.
Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Sodium: \<0.95\LLN or \>1.05\ULN or if preRx\<LLN, \<0.95\preRx or \>ULN, or if preRx\>ULN,\>1.05\preRx or \<LLN. Potassium,serum: \<0.9\LLN or \>1.1\ULN or if preRx\<LLN, use \<0.9\preRx or \>ULN or if preRx\>ULN, 1.1\preRx or \<LLN. Phosphorus: 0.75\LLN or 1.25\ULN or, if preRx\<LLN, \<0.67\*preRx or \>ULN or, if preRx\>ULN, \<LLN.
Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality	Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period	LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality: .
Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	preRX=pretreatment. For all values analyzed (protein, urine; glucose, urine; blood, urine: leukocyte esterase, urine; white blood cells, urine; red blood cells, urine): If missing preRx, use \>=2 or, if value \>= 4, or if preRx=0 or 0.5, use \>=2 or, if preRx= 1, use \>=3 or, if preRx=2 or 3, use \>=4.
Number of Participants With Adverse Events of Special Interest	Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period	AEs of special interest are AEs that may be associated with the use of immunomodulatory drugs, such as infections, malignancies, autoimmune disorders, and injection reactions (defined as local injection site reactions and systemic injection reactions occurring within 24 hours of subcutaneous injection).
Mean Sitting Systolic and Diastolic Blood Pressure (BP)	Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821	BP was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.
Mean Heart Rate	Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821	Heart rate was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.
Mean Temperature	Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821	Temperature was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.

Secondary Outcome Measures

Name	Time	Method
Mean Trough Serum Concentration (Cmin) of Abatacept	Days 29, 85, 57, and 85	Cmin of abatacept was determined from serum samples.
Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) at Day 85	Day 1 (Baseline) through Day 85	Using the ELISA, any positive (titer of 400 or greater) postbaseline sample was classified as positive immunogenicity. The percentage of participants with at least 1 positive antibody response (anti-abatacept and/or anti-CTLA4-T) during the 85 days was tabulated by antibody specificity and overall.
Percentage of Participants With A Positive Anti-abatacept Response (Based on Electrochemiluminescence [ECL] Immunoassay) at Day 85	Day 1 (Baseline) through Day 85	Number of participants was tabulated using ECL assay with at least 1 positive abatacept-induced immunogenic response (CTLA4 and possibly Ig, Ig and/or Junction Region) in the first 85 days. Positive response (titers \>10) included: * A missing baseline immunogenicity measurement and a positive immunogenicity response postbaseline * A negative baseline immunogenicity response and a positive immunogenicity response postbaseline * A positive baseline immunogenicity response and a positive immunogenicity response postbaseline that has a titer value strictly greater than the baseline titer value
Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time	Day 1 (Baseline) through Day 1093	The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time:	Day 1 (Baseline) through Day 1093	LDAS is defined as DAS 28-CRP ≤3.2. DAS 28-CRP remission is defined as DAS 28-CRP \<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time	Day 1 (Baseline) to Day 1093	The HAQ-DI assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories is divided by the number of categories answered, yielding a score from 0-3.

Trial Locations

Locations (19): Rheumatology Associates Of N. Al, P.C.
🇺🇸
Huntsville, Alabama, United States
Desert Medical Advances
🇺🇸
Palm Desert, California, United States
Valerius Medical Group &Research Ctr. Of Greater Long Beach
🇺🇸
Long Beach, California, United States
Allergy & Rheumatology Medical Clinic, Inc.
🇺🇸
La Jolla, California, United States
Inland Rheumatology Clinical Trials Inc.
🇺🇸
Upland, California, United States
Arthritis & Rheumatic Disease Specialties
🇺🇸
Aventura, Florida, United States
Innovative Health Research
🇺🇸
Las Vegas, Nevada, United States
Physician Research Collaboration, Llc
🇺🇸
Lincoln, Nebraska, United States
The Center For Rheumatology, Llp
🇺🇸
Albany, New York, United States
Diagnostic Rheumatology And Research,Pc
🇺🇸
Indianapolis, Indiana, United States
Graves Gilbert Clinic
🇺🇸
Bowling Green, Kentucky, United States
Unifour Medical Research
🇺🇸
Hickory, North Carolina, United States
Walter F. Chase, Md
🇺🇸
Austin, Texas, United States
The Arthritis Clinic & Carolina Bone & Joint
🇺🇸
Charlotte, North Carolina, United States
Cincinnati Rheumatic Disease Study Group
🇺🇸
Cincinnati, Ohio, United States
Portland Rheumatology Clinic
🇺🇸
Lake Oswego, Oregon, United States
Rheumatic Disease Associates, Ltd.
🇺🇸
Willow Grove, Pennsylvania, United States
Arthritis Centers Of Texas
🇺🇸
Dallas, Texas, United States
Local Institution
🇲🇽
San Luis Potosi, Mexico