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

Rüdiger B. Müller

Status and phase: Completed; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: IV Abatacept

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01846975

A-BREAK

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

49 participants in 1 patient group

Switch from SC to IV Abatacept and back

Experimental group

Description:

Transition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break.

Treatment:

Drug: IV Abatacept