Study to Assess Steady-State Trough Concentrations, Safety, and Immunogenicity of Abatacept After Subcutaneous (SC) Administration to Subjects With Rheumatoid Arthritis (RA)

NCT00254293 | Completed Phase 1 Results

• 1 other identifier: IM101-063
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to study serum levels of Abatacept after subcutaneous dosing in subjects with RA.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS)

  Participants received abatacept while also receiving DMARDS over a short term (ST) 12 Week period. To eliminate contribution from the IV loading dose of abatacept during the short term study period, Cmin values were selected from Days 71 to 85, when contribution from IV was negligible. Minimum trough serum concentration of abatacept (Cmin) was measured in micrograms/milliliter (µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.

  Days 71 to 85

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Reported During the Variable Dosing Phase of the Long Term Period (LTE)

  AEs during variable dose phase of LTE + 56 days post last dose in the variable dose phase or start of the fixed dose phase, which ever came first; includes deaths reported during the variable dose phase including those that occurred greater than 56 days after last dose. Medical Dictionary for Regulatory Activities (MedDRA) version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug. Data presented by treatment the participant was randomized to and not what they actually received.

  Day 85 to 56 days post last dose

• Number of Participants With Pre-specified AEs of Special Interest in the Variable Dosing Phase of Long Term Extension (LTE)

  LTE period with variable abatacept dosing starting on Day 85 and continuing until Day 533 when LTE fixed dosing started. AEs of special interest: infection and/or infestation; neoplasms (malignant); pre-specified autoimmune disorder; infusional AEs (peri-infusional: pre-specified AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: pre-specified AEs occurring during the first hour after the start of the IV loading dose; systemic injection site reactions (SIR): pre-specified AEs for SIR; local injection site reaction: pre-specified AEs for local site reaction. Data are presented by treatment the participant was randomized to and not what they actually received.

  Day 85 to Day 533

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Summarized Over the Entire Long Term Extension (LTE) Period (Both Variable and Fixed Dosing)

  On Day 85 participants rolled over into the LTE with variable dose phase first and at Day 533, a fixed dose phase of 125 mg abatacept SC weekly, irrespective of body weight. This summary includes AEs reported during entire LTE treatment plus 56 days post last dose; includes all deaths reported during the LTE including those that occurred greater than 56 days after last dose. MedDRA version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug.

  Day 533 to 56 Days Post last dose

Secondary Outcomes (12)

• Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS

  Day 71 to Day 78

• Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS

  Day 71 to Day 78

• Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo

  Day 1 to Day 85 (or early termination)

• Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks

  Day 1 to Day 85 (or early termination)

• Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration

  Day 1 to Day 85 (or early termination)

Study Arms (6)

Group 1 (weight < 60 kg)

PLACEBO COMPARATOR

Drug: Abatacept or Placebo (both as IV & SC Solution)

Group 2 (weight < 60 kg)

PLACEBO COMPARATOR

Drug: Abatacept or Placebo (both as IV & SC Solution)

Group 3 (weight 60-100 kg)

PLACEBO COMPARATOR

Drug: Abatacept or Placebo (both as IV & SC solution)

Group 4 (weight > 100 kg)

PLACEBO COMPARATOR

Drug: Abatacept or Placebo (both as IV & SC solution)

Group 5 (weight > 100 kg)

PLACEBO COMPARATOR

Drug: Abatacept or Placebo (both as IV & SC solution)

Abatacept

EXPERIMENTAL

Long Term

Drug: Abatacept

Interventions

Abatacept or Placebo (both as IV & SC solution) DRUG

Abatacept \& Placebo as IV \& SC solution, IV/SC, Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks) or Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), 12 weeks then long term extension (LTE).

Also known as: Orencia

Group 1 (weight < 60 kg)

Abatacept DRUG

Solution in pre-filled syringes, Subcutaneously, 125 mg, Weekly

Abatacept

Eligibility Criteria

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

You may qualify if:

• Meet ARA criteria for diagnosis of RA with active disease.
• RA diagnosis for at least 1 year.
• \> = 6 swollen joints.
• \> = 8 tender joints.
• Taking methotrexate (MTX) or MTX plus not more than 1 added oral DMARD for \> = 3 months and stable for 28 days prior to dosing.

You may not qualify if:

• Serious acute or bacterial infection in last 3 months.
• Chronic or recurrent bacterial infections.
• History of TB within previous 3 years or old TB not adequately treated.
• Specific lab test abnormalities
• History of cancer within 5 years.
• Exposure to CTLA4Ig (Cytotoxic T-lymphocyte (T-cell)-associated antigen 4Ig), belatacept, rituximab, efalizumab, alefacept, or other investigational drug or biologic.
• Treatment with hydroxychloroquine, azathioprine, leflunomide, immunoadsorption columns, mycophenolate mofetil, cyclosporine, D-Penicillamine or calcineurin inhibitors.
• Exposure to live vaccines.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (5)

Orlando Clinical Research Center

Orlando, Florida, 32806, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

New Orleans Center For Clinical Research

New Orleans, Louisiana, 70119, United States

Location

Davita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

The Arthritis Clinic & Carolina Bone & Joint

Charlotte, North Carolina, 28210, United States

Location

Related Publications (1)

• Westhovens R, Kremer JM, Moreland LW, Emery P, Russell AS, Li T, Aranda R, Becker JC, Qi K, Dougados M. Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: a 5-year extended phase IIB study. J Rheumatol. 2009 Apr;36(4):736-42. doi: 10.3899/jrheum.080813. Epub 2009 Feb 27.

  PMID: 19273451 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

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

Limitations and Caveats

Error resulted in 4 participants being treated with study drug they were not randomized to receive. ST data were summarized by study drug participants actually received while LT data were summarized by what participants were randomized to receive.

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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2005
• First Posted: November 16, 2005
• Study Start: January 1, 2006
• Primary Completion: May 1, 2007
• Study Completion: July 1, 2012
• Last Updated: April 8, 2014
• Results First Posted: April 8, 2014

Record last verified: 2014-03

Locations

US (5)