Text Size

Phase IIIB Switching From Intravenous to Subcutaneous Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00663702
First received: April 18, 2008
Last updated: February 22, 2012
Last verified: February 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Arthritis, Rheumatoid
 Drug: Abatacept
 Phase 3

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

Resource links provided by NLM:

Drug Information available for: Abatacept
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, and Death As Outcome Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    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 AEs of Special Interest Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    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. 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 or >7.50*10^3 c/uL.

  • Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    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. Bilirubin, total (mg/dL) >2*ULN or if preRX>ULN,use 4*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 Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Sodium: <.95*LLN or >1.05*ULN or if preRX<LLN, <.95*preRX or >ULN, or if preRX>ULN,>1.05*preRX or <LLN. Potassium,serum: <.9*LLN or >1.1*ULN or if preRX<LLN, use <.9*preRX or >ULN or if preRX>ULN, 1.1*preRX or <LLN. Chloride: <.9*LLN or >1.1*ULN or, if preRX<LLN, <.9*preRX or >ULN or, if preRX>ULN, >1.1*preRX or <LLN. Calcium: <.8*LLN or >1.2*ULN or, if preRX<LLN, <.67*preRX or >ULN or if preRX>ULN, >1.3*preRX or <LLN. Phosphorus: .75*LLN or 1.25*ULN or, if preRX<LLN, <.67*preRx or >ULN or, if preRX>ULN, <LLN.

  • Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality: Glucose serum (mg/dL): low <65; glucose serum, high: >220; glucose serum fasting (mg/dL): <0.8*LLN or >1.5*ULN, or if preRX<LLN, use <0.8*preRX or >ULN, or if preRX>ULN, use >2.0*preRX or <LLN; total protein (g/dL): <0.9*LLN or >1.1*ULN, or if preRX<LLN, use 0.9*preRX or >ULN, or if preRX >ULN, use 1.1*preRX or <LLN; albumin (g/dL): <0.9*LLN, or if preRX<LLN, use <0.75*preRX; uric acid (mg/dL): >1.5*ULN, or if preRX>ULN, use >2*preRX. .

  • Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
    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.

  • Mean Sitting Systolic and Diastolic Blood Pressure (BP) Through Day 85 [ Time Frame: Before injection on Days 1, 29, 57, and 85 ] [ Designated as safety issue: Yes ]
  • Mean Heart Rate Through Day 85 [ Time Frame: Before injection on Days 1, 26, 57, and 85 ] [ Designated as safety issue: Yes ]
  • Mean Temperature Through Day 85 [ Time Frame: Before injection on Days 1, 29, 57, and 85 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean Trough Serum Concentration (Cmin) of Abatacept Through Day 85 [ Time Frame: Days 29, 85, 57, and 85 ] [ Designated as safety issue: No ]
    Cmin of abatacept was determined from serum samples.

  • Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: No ]
    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) Through Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: No ]

    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


Enrollment: 123
Study Start Date: May 2008
Study Completion Date: January 2012
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Abatacept
Subcutaneous injection, 125 mg/mL, once weekly, 48 months
Other Names:
  • Orencia
  • BMS-188667

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00663702

  Show 30 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00663702     History of Changes
Other Study ID Numbers: IM101-185
Study First Received: April 18, 2008
Results First Received: January 19, 2012
Last Updated: February 22, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Mexico: National Institute of Public Health, Health Secretariat

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
 Abatacept
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2013