Phase IIIB Switching From Intravenous to Subcutaneous Study

Arthritis, Rheumatoid Clinical Trial

Official title:

A Phase 3B Multi-center Open-Label Study to Evaluate the Safety of Abatacept in Subjects Who Switch From Intravenous to Subcutaneous Abatacept Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00663702
• Other study ID #: IM101-185
• Status: Completed
• Phase: Phase 3
• First received: April 18, 2008
• Last updated: February 17, 2015
• Start date: May 2008
• Est. completion date: January 2012

Study information

• Verified date: February 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaMexico: National Institute of Public Health, Health Secretariat
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: January 2012
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid

Intervention

Drug:
• Abatacept
Subcutaneous injection, 125 mg/mL, once weekly, 48 months

Locations

Country	Name	City	State
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Kitchener	Ontario
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Quebec
Canada	Local Institution	St. John'S	Newfoundland and Labrador
Canada	Local Institution	Toronto	Ontario
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Nuevo Leon
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Tijuana	Baja California
United States	The Center For Rheumatology, Llp	Albany	New York
United States	Walter F. Chase, Md	Austin	Texas
United States	Arthritis & Rheumatic Disease Specialties	Aventura	Florida
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	The Arthritis Clinic & Carolina Bone & Joint	Charlotte	North Carolina
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	Arthritis Centers Of Texas	Dallas	Texas
United States	Unifour Medical Research	Hickory	North Carolina
United States	Rheumatology Associates Of N. Al, P.C.	Huntsville	Alabama
United States	Diagnostic Rheumatology And Research,Pc	Indianapolis	Indiana
United States	Allergy & Rheumatology Medical Clinic, Inc.	La Jolla	California
United States	Portland Rheumatology Clinic	Lake Oswego	Oregon
United States	Innovative Health Research	Las Vegas	Nevada
United States	Physician Research Collaboration, Llc	Lincoln	Nebraska
United States	Valerius Medical Group &Research Ctr. Of Greater Long Beach	Long Beach	California
United States	Desert Medical Advances	Palm Desert	California
United States	Inland Rheumatology Clinical Trials Inc.	Upland	California
United States	Rheumatic Disease Associates, Ltd.	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Day 1 (Baseline) through Day 85	Yes
Primary	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	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.	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	Yes
Primary	Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality	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	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	Yes
Primary	Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality	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.	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	Yes
Primary	Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality	LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Sodium: <0.95*LLN or >1.05*ULN or if preRx	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	Yes
Primary	Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality	LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality: .	Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period	Yes
Primary	Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality	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.	Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period	Yes
Primary	Number of Participants With Adverse Events of Special Interest	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).	Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period	Yes
Primary	Mean Sitting Systolic and Diastolic Blood Pressure (BP)	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.	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	Yes
Primary	Mean Heart Rate	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.	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	Yes
Primary	Mean Temperature	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.	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	Yes
Secondary	Mean Trough Serum Concentration (Cmin) of Abatacept	Cmin of abatacept was determined from serum samples.	Days 29, 85, 57, and 85	No
Secondary	Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) at 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.	Day 1 (Baseline) through Day 85	No
Secondary	Percentage of Participants With A Positive Anti-abatacept Response (Based on Electrochemiluminescence [ECL] Immunoassay) at 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	Day 1 (Baseline) through Day 85	No
Secondary	Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time	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.)	Day 1 (Baseline) through Day 1093	No
Secondary	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:	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.)	Day 1 (Baseline) through Day 1093	No
Secondary	Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time	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.	Day 1 (Baseline) to Day 1093	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm