Introducing a Single IV Abatacept Treatment in RA Patients Currently Receiving Weekly SC Abatacept to Simulate a Holiday (A-BREAK)

March 2, 2015 updated by: Rüdiger B. Müller

A Phase IV, Open Label Study Introducing a Single IV Treatment With Abatacept in Patients With Rheumatoid Arthritis Currently Receiving Weekly Injections of SC Abatacept to Simulate a Holiday or Patient Vacation

RA (rheumatoid arthritis) patients effectively treated weekly with SC (subcutaneous) Abatacept will be switched to IV (intravenous) Abatacept and restarted with SC Abatacept four after IV application. The investigators hypothesize that a switch from SC- to IV-abatacept and back in patients with low disease activity is safe and not associated with a worsening of the disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Abatacept is a recombinant fusion protein composed of the Fc region of the Immunoglobulin IgG1 fused to the extracellular domain human cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) modified to prevent antibody-dependent cellular cytotoxicity and complement fixation. Abatacept is a selective co-simulation modulator that inhibits the co-stimulation of T-cells. Abatacept is currently approved for use in rheumatoid arthritis (RA) and is useful in symptom reduction and delaying the progression of structural damage.

RA is a chronic inflammatory autoimmune disease. With the introduction of biological disease-modifying antirheumatic drugs (DMARDs) (biologics), the options for the treatment of RA have dramatically changed. Abatacept is currently the only biologic to be available in both, a subcutaneous (SC) and intravenous (IV) formulation. The efficacy and safety profile of IV-Abatacept has been well established in the last years and clinical trials comparing SC-Abatacept with IV-Abatacept have clearly demonstrated an equal efficacy and safety profile. Importantly, switching from IV- to SC-Abatacept appears to be associated with a persisting good efficacy of Abatacept and no increase of adverse events (AE). On the other hand, however, switching from SC- to IV-Abatacept has not been the subject of clinical trials.

This Phase IV study is aimed at reviewing both the transition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break. Holiday seasons can present a major problem to RA patients treated with weekly subcutaneous biologics, including SC-Abatacept. Therefore an evaluation into the use of IV-Abatacept treatment to cover a 4 week break may present an acceptable treatment alternative for this patient population.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • St. Gallen, Switzerland, 9007
        • Kantonsspital St. Gallen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female subjects aged 18 years or older at the time of consent
  2. Able to give informed consent
  3. Patients classified as RA according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria (Aletaha D et al, 2010)
  4. Patient treated with weekly SC-Abatacept for at least 3 months prior to study screening
  5. Effective control of disease activity as defined by DAS-28 (ESR) < 3.2 (LDAS)
  6. Available for the whole duration of the study
  7. Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for the duration of the study (up to 168 days post the IV infusion of Abatacept). They also must have a negative pregnancy test upon entry into the study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
  8. Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrolment, for the duration of the study (up to 168 days post the IV infusion of Abatacept)

Exclusion Criteria:

  1. Subjects who have previously received >2 biologic DMARDs
  2. Pregnant or breastfeeding women or such with a child-bearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period (up to Day 168/Safety follow-up visit)
  3. Subjects with active vasculitis of a major organ system, with the exception of rheumatoid nodules
  4. Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to RA and which, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study
  5. Subjects with a history of cancer in the last 5 years, or with a current screening suspicious for cancer, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
  6. Subjects with evidence of active or latent bacterial (e.g. tuberculosis) or viral infections (e.g. Human Immunodeficiency Virus (HIV) at the time of potential enrolment
  7. Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before the informed consent document was signed
  8. Subjects who have received any live vaccines within 3 months of the anticipated first dose of study medication
  9. Having participated in another drug or an interventional study within 30 days preceding the present study screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Switch from SC to IV Abatacept and back
Transition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break.
Drug: IV Abatacept
Transition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break.
Other Names:
  • Switch from SC to IV Abatacept and back

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Is switching from weekly SC injections of Abatacept to a single IV injection to cover a 4-week period an effective treatment for maintaining the disease state of patients with RA.
Time Frame: 4 weeks
Percentage of patients remaining with or less than Low Disease Activity Score (LDAS (Machold KP et al, 2003).) at Day 28. LDAS is defined as a disease activity score-28 (DAS-28 (ESR) (Prevoo ML et al, 1995)) of less than 3.2. The DAS-28 (ESR) is defined by the number of tender and swollen joints calculated from 28 joints mainly from the upper limbs, the erythrocyte sedimentation rate (ESR) and the patient´s global assessment of disease activity (Wells, 2009).
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Is switching from SC- to IV-Abatacept and back within 1 month safe at 84 days after the IV-Abatacept treatment.
Time Frame: 84 days
Occurrence of AEs after 84 days
84 days
Is switching from SC- to IV-Abatacept and back within 1 month safe at 168 days after the IV-Abatacept treatment.
Time Frame: 168 days
Occurrence of AEs after 168 days
168 days
Is switching from SC- to IV-Abatacept and back within 1 month effective for maintaining the disease state of patients with RA at 84 days after the IV-Abatacept treatment.
Time Frame: 84 days
  1. Percentage of patients still with or less than LDAS at Day 84
  2. Number of tender and swollen joints (68/66 joint count) at Day 84 compared to baseline
  3. Percentage of patients remaining on therapy with SC-Abatacept at Day 84
84 days
Is switching from SC- to IV-Abatacept and back within 1 month effective for maintaining the disease state of patients with RA at 168 days after the IV-Abatacept treatment.
Time Frame: 168 days
  1. Percentage of patients still with or less than LDAS at Day 168
  2. Number of tender and swollen joints (68/66 joint count) at Day 168 compared to baseline
  3. Percentage of patients remaining on therapy with SC-Abatacept at Day 168
168 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical disease activity and patient related outcome parameters over the study period Does IV-Abatacept pre-exposition influence the occurrence of AEs or the evolving disease activity
Time Frame: 168 days
  1. Review of Health Assessment Questionnaire (HAQ-DI) score, patients' global assessment of disease activity and pain, physicians' global assessment over the study period
  2. Percentage of patients remaining with or less than LDAS at Days 28, 84 and 168 compared to their pre-exposure to IV-Abatacept
  3. Occurrence of severe AEs over the study period (168 days) according to their pre-exposure to IV-Abatacept
  4. Comparison of the first line and second/later line biologic treatment using a non-metric test comparing the two groups for change in DAS-28 (ESR) and number of patients still with or less than LDAS
  5. Change in average DAS-28 (ESR) for RA compared to baseline over time at Days 28, 84 and 168
168 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rüdiger B. Müller

Collaborators

Bristol-Myers Squibb

Investigators

  • Study Chair: Ruediger B Mueller, MD, Cantonal Hospital of St. Gallen
  • Study Director: Johannes von Kempis, Prof., Cantonal Hospital of St. Gallen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

April 19, 2013

First Submitted That Met QC Criteria

May 1, 2013

First Posted (Estimate)

May 6, 2013

Study Record Updates

Last Update Posted (Estimate)

March 4, 2015

Last Update Submitted That Met QC Criteria

March 2, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A-BREAK

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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