Rheumatoid ArthritisPhase 4A-BREAKNCT01846975
Introducing a Single IV Abatacept Treatment in RA Patients Currently Receiving Weekly SC Abatacept to Simulate a Holiday
A Phase 4 study testing IV Abatacept in people with Rheumatoid Arthritis, run by Rüdiger B. Müller at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- IV Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteSwitzerland
- Study dates
- May 2013to Jan 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects aged 18 years or older at the time of consent
- Able to give informed consent
- Patients classified as RA according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria (Aletaha D et al, 2010)
- Patient treated with weekly SC-Abatacept for at least 3 months prior to study screening
- Effective control of disease activity as defined by DAS-28 (ESR) < 3.2 (LDAS)
- Available for the whole duration of the study
- 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.
- 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)
Who cannot join
- Subjects who have previously received >2 biologic DMARDs
- 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)
- Subjects with active vasculitis of a major organ system, with the exception of rheumatoid nodules
- 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
- 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
- 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
Show all 9Show fewer
- Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before the informed consent document was signed
- Subjects who have received any live vaccines within 3 months of the anticipated first dose of study medication
- Having participated in another drug or an interventional study within 30 days preceding the present study screening
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Kantonsspital St. Gallen
Sankt Gallen, Canton of St. Gallen, 9007
About this study
Official title: 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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- IV Abatacept
- Keywords
- Abatacept, Low disease activity, Intravenous, Subcutaneous, Rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV AbataceptDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Switch from SC to IV Abatacept and back | Experimental | Transition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break. Receives: Drug: IV Abatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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).
Measured: 4 weeks
Secondary outcomes (4)
Is switching from SC- to IV-Abatacept and back within 1 month safe at 84 days after the IV-Abatacept treatment.
Occurrence of AEs after 84 days
Measured: 84 days
Is switching from SC- to IV-Abatacept and back within 1 month safe at 168 days after the IV-Abatacept treatment.
Occurrence of AEs after 168 days
Measured: 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.
- Percentage of patients still with or less than LDAS at Day 84
- Number of tender and swollen joints (68/66 joint count) at Day 84 compared to baseline
- Percentage of patients remaining on therapy with SC-Abatacept at Day 84
Measured: 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.
- Percentage of patients still with or less than LDAS at Day 168
- Number of tender and swollen joints (68/66 joint count) at Day 168 compared to baseline
- Percentage of patients remaining on therapy with SC-Abatacept at Day 168
Measured: 168 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2013 (estimated)
- Study startMay 2013
- Primary completionDec 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rüdiger B. Müller
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Rüdiger B. Müller, Cantonal Hospital of St. Gallen
- Investigators
- Ruediger B Mueller, MD, Study chair, Cantonal Hospital of St. GallenJohannes von Kempis, Prof., Study director, Cantonal Hospital of St. Gallen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01846975
- Sponsor's protocol ID
- A-BREAK
- Acronym
- A-BREAK
- Status last verified
- Mar 2015
- First submitted
- 19 Apr 2013
- Last updated
- 4 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Genovese MC, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon-Campos JA, Porawska W, Box J, Legerton C 3rd, Nasonov E, Durez P, Aranda R, Pappu R, Delaet I, Teng J, Alten R. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum. 2011 Oct;63(10):2854-64. doi: 10.1002/art.30463.
PubMed 21618201Kaine J, Gladstein G, Strusberg I, Robles M, Louw I, Gujrathi S, Pappu R, Delaet I, Pans M, Ludivico C. Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study). Ann Rheum Dis. 2012 Jan;71(1):38-44. doi: 10.1136/annrheumdis-2011-200344. Epub 2011 Sep 13.
PubMed 21917824Keystone EC, Kremer JM, Russell A, Box J, Abud-Mendoza C, Elizondo MG, Luo A, Aranda R, Delaet I, Swanink R, Gujrathi S, Luggen M. Abatacept in subjects who switch from intravenous to subcutaneous therapy: results from the phase IIIb ATTUNE study. Ann Rheum Dis. 2012 Jun;71(6):857-61. doi: 10.1136/annrheumdis-2011-200355. Epub 2012 Feb 2.
PubMed 22302417Mueller RB, Gengenbacher M, Richter S, Dudler J, Moller B, von Kempis J. Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK). Arthritis Res Ther. 2016 Apr 14;18:88. doi: 10.1186/s13075-016-0985-2.
PubMed 27074795
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01846975
- Acronym / sponsor ID
- A-BREAK / A-BREAK
- Conditions
- Rheumatoid Arthritis
- Keywords
- Abatacept, Low disease activity, Intravenous, Subcutaneous, Rheumatoid arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Rüdiger B. MüllerUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- May 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 6 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Switch from SC to IV Abatacept and back | Experimental | Drug: IV AbataceptTransition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female subjects aged 18 years or older at the time of consent
- Able to give informed consent
- Patients classified as RA according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria (Aletaha D et al, 2010)
- Patient treated with weekly SC-Abatacept for at least 3 months prior to study screening
- Effective control of disease activity as defined by DAS-28 (ESR) < 3.2 (LDAS)
Key exclusion criteria (9 listed)
- Subjects who have previously received >2 biologic DMARDs
- 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)
- Subjects with active vasculitis of a major organ system, with the exception of rheumatoid nodules
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV AbataceptAlso: Switch from SC to IV Abatacept and backTransition from weekly SC- to a single IV-Abatacept but also the return to weekly SC treatments after a 4 week break. | Drug | Switch from SC to IV Abatacept and back |
Primary outcome
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 secondary outcomes
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2015.
- Background: PubMed 21618201Genovese MC, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon-Campos JA, Porawska W, Box J, Legerton C 3rd, Nasonov E, Durez P, Aranda R, Pappu R, Delaet I, Teng J, Alten R. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum. 2011 Oct;63(10):2854-64. doi: 10.1002/art.30463.
- Background: PubMed 21917824Kaine J, Gladstein G, Strusberg I, Robles M, Louw I, Gujrathi S, Pappu R, Delaet I, Pans M, Ludivico C. Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study). Ann Rheum Dis. 2012 Jan;71(1):38-44. doi: 10.1136/annrheumdis-2011-200344. Epub 2011 Sep 13.
- Background: PubMed 22302417Keystone EC, Kremer JM, Russell A, Box J, Abud-Mendoza C, Elizondo MG, Luo A, Aranda R, Delaet I, Swanink R, Gujrathi S, Luggen M. Abatacept in subjects who switch from intravenous to subcutaneous therapy: results from the phase IIIb ATTUNE study. Ann Rheum Dis. 2012 Jun;71(6):857-61. doi: 10.1136/annrheumdis-2011-200355. Epub 2012 Feb 2.
- Derived from this study: PubMed 27074795Mueller RB, Gengenbacher M, Richter S, Dudler J, Moller B, von Kempis J. Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK). Arthritis Res Ther. 2016 Apr 14;18:88. doi: 10.1186/s13075-016-0985-2.
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruediger B Mueller, MD study chair
Cantonal Hospital of St. Gallen
Johannes von Kempis, Prof. study director
Cantonal Hospital of St. Gallen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing IV Abatacept in people with Rheumatoid Arthritis, run by Rüdiger B. Müller at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01846975, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2015.