Phase IIIB Switching From Intravenous to Subcutaneous Study

NCT00663702 | Completed Phase 3 Results

• 1 other identifier: IM101-185
• Study Type: interventional
• Target: 123
• Locations: 3 countries
• Sites: 30

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

Conditions

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (11)

• 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

• 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

• 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\<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.

  Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period

• 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

• 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\<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.

  Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (6)

• Mean Trough Serum Concentration (Cmin) of Abatacept

  Days 29, 85, 57, and 85

• 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

• Percentage of Participants With A Positive Anti-abatacept Response (Based on Electrochemiluminescence [ECL] Immunoassay) at Day 85

  Day 1 (Baseline) through Day 85

• Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time

  Day 1 (Baseline) through Day 1093

• 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

Study Arms (1)

1

EXPERIMENTAL

Drug: Abatacept

Interventions

Abatacept DRUG

Subcutaneous injection, 125 mg/mL, once weekly, 48 months

Also known as: Orencia, BMS-188667

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (30)

Rheumatology Associates Of N. Al, P.C.

Huntsville, Alabama, 35801, United States

Location

Allergy & Rheumatology Medical Clinic, Inc.

La Jolla, California, 92037, United States

Location

Valerius Medical Group &Research Ctr. Of Greater Long Beach

Long Beach, California, 90806, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

Inland Rheumatology Clinical Trials Inc.

Upland, California, 91786, United States

Location

Arthritis & Rheumatic Disease Specialties

Aventura, Florida, 33180, United States

Location

Diagnostic Rheumatology And Research,Pc

Indianapolis, Indiana, 46227, United States

Location

Graves Gilbert Clinic

Bowling Green, Kentucky, 42101, United States

Location

Physician Research Collaboration, Llc

Lincoln, Nebraska, 68516, United States

Location

Innovative Health Research

Las Vegas, Nevada, 89128, United States

Location

The Center For Rheumatology, Llp

Albany, New York, 12206, United States

Location

The Arthritis Clinic & Carolina Bone & Joint

Charlotte, North Carolina, 28210, United States

Location

Unifour Medical Research

Hickory, North Carolina, 28601, United States

Location

Cincinnati Rheumatic Disease Study Group

Cincinnati, Ohio, 45219, United States

Location

Portland Rheumatology Clinic

Lake Oswego, Oregon, 97035, United States

Location

Rheumatic Disease Associates, Ltd.

Willow Grove, Pennsylvania, 19090, United States

Location

Walter F. Chase, Md

Austin, Texas, 78705, United States

Location

Arthritis Centers Of Texas

Dallas, Texas, 75246, United States

Location

Local Institution

Edmonton, Alberta, T6G 2S2, Canada

Location

Local Institution

St. John's, Newfoundland and Labrador, A1A 5E8, Canada

Location

Local Institution

Kitchener, Ontario, N2M 5N6, Canada

Location

Local Institution

Toronto, Ontario, M5G 1X5, Canada

Location

Local Institution

Montreal, Quebec, H2L 1S6, Canada

Location

Local Institution

Québec, Quebec, G1V 3M7, Canada

Location

Local Institution

Tijuana, Estado de Baja California, 22320, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44690, Mexico

Location

Local Institution

Mexico City, Mexico City, 06726, Mexico

Location

Local Institution

Mexico City, Mexico City, 14080, Mexico

Location

Local Institution

Nuevo León, Nuevo León, 64020, Mexico

Location

Local Institution

San Luis Potosí City, San Luis Potosí, 78240, Mexico

Location

Related Publications (1)

• Alten R, Bingham CO 3rd, Cohen SB, Curtis JR, Kelly S, Wong D, Genovese MC. Antibody response to pneumococcal and influenza vaccination in patients with rheumatoid arthritis receiving abatacept. BMC Musculoskelet Disord. 2016 May 26;17:231. doi: 10.1186/s12891-016-1082-z.

  PMID: 27229685 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

clinical.trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2008
• First Posted: April 22, 2008
• Study Start: May 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2012
• Last Updated: March 9, 2015
• Results First Posted: March 26, 2012

Record last verified: 2015-02

Locations

CA (6); US (18); ME (6)