Rheumatoid ArthritisRANCT02053727
Abatacept vs Placebo in RA Patients With Hepatitis B on Entecavir Background
A study testing Abatacept in people with Rheumatoid Arthritis and Chronic Hepatitis B, run by University of California, Los Angeles at 1 site in United States.
Trial summary
The purpose of this study is to investigate whether the combination of abatacept along with entecavir (the study drugs) is safe and effective in treating symptoms related to rheumatoid arthritis (RA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis, Chronic Hepatitis B
- What is being tested?
- Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to 12 Jun 2018
- Phase
- Interventional
- 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
- Diagnosis of RA.
- Baseline CDAI >10 with TJC (Tender Joint Count) > 4 and SJC (Swollen Joint Count) > 2.
- Chronic Hepatitis B as defined by a history of patients with a HBsAg positive for at least 6 months with undetectable HBV DNA; or a history of patients with negative HBsAg and positive HBcAb or HBsAb, with undetectable HBV DNA.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening,) negative liver imaging as shown by ultrasound, computerized tomography or magnetic resonance imaging within 24 weeks of screening. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging and shown not to have HCC on CT or MRI before they can be enrolled.
- Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs (Non-Steroidal Anti-inflammatory Drugs) are permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to and including at baseline.
- Men and women, >= 18 years of age.
Who cannot join
- Women who are pregnant or breastfeeding. Sexually active fertile men not using effective birth control if their partners are WOCBP (Women of Child Bearing Potential).
- Target Disease Exceptions
- Rheumatic autoimmune disease other than RA; fibromyalgia or keratoconjunctivitis/xerostomia are allowed, as long as these will not confound the CLINICAL EFFICACY OUTCOMES.
- Medical History and Concurrent Diseases
- Subjects who are impaired, incapacitated, or incapable of completing study-related assessments.
- Subjects who underwent previous MCP (metacarpophalangeal) arthroplasty, have such a procedure scheduled, or anticipate the need for such a procedure during the study.
Show all 26Show fewer
- Major surgery (including joint surgery) within 8 weeks prior to screening
- Subjects with active vasculitis of a major organ system, with the exception of rheumatoid nodules or minor rheumatoid vasculitis lesions of the skin
- Subjects with current uncontrolled symptoms of severe, progressive, or uncontrolled renal, hepatic hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, including Cirrhosis with Child-Pugh Class >=2 or COPD (chronic obstructive pulmonary disease) with FEV1 (forced expiratory volume in 1 second) /FVC (forced vital capacity) < 0.6
- Female subjects who have had a recent breast cancer screening that is suspicious for malignancy and where the diagnosis is not excluded.
- Subjects who currently abuse drugs or alcohol. i) Subjects with evidence of active or latent bacterial or viral infections at the time of potential enrollment, including HIV.
- 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.
- Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection.
- Subjects at risk for tuberculosis (TB) or not treated for latent TB is tested positive.
- Subjects who are positive for hepatitis C antibody if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay.
- Subjects who have abnormal laboratory values
- Prohibited Treatments and/or Therapies
- Subjects who have at any time received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose.
- Any concomitant biologic DMARD, such as anakinra.
- Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to CAMPATH, anti-CD4 (cluster of differentiation 4), anti-CD5, anti-CD3, and anti-CD19.
- Anti-CD20 treatment within the last 6 months (OK to include if they were dosed > 6 months ago).
- Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil, within <= 4 weeks prior to baseline.
- Treatment with etanercept within 2 weeks, infliximab/certolizumab/golimumab/adalimumab with <=8 weeks, anakinra within <=1 week prior to baseline.
- Previous abatacept use.
- Treatment with sulfasalazine within < 4 weeks prior to baseline
Trial locations and contacts
1 site in 1 country.
United States1 site
Division of Rheumatology, UCLA David Geffen School of Medicine
Los Angeles, California, 90095
About this study
Official title: Pilot Study to Evaluate Subcutaneous Abatacept vs Placebo in RA Patients With Hepatitis B on Entecavir Background- a Pilot, Double-blind, Placebo-controlled, Randomized, Controlled Trial.
The purpose of this study is to investigate whether the combination of abatacept along with entecavir (the study drugs) is safe and effective in treating symptoms related to rheumatoid arthritis (RA).
Abatacept, given in an intravenous (IV - injected into a vein) as well as subcutaneous form, is approved by the FDA for the treatment of RA. In this research, abatacept will be given by injection. A subcutaneous injection is an injection given under the skin.
Read more
Entecavir, to be taken by mouth, is approved by the FDA for the treatment of hepatitis B.
The study is divided into the following time periods:
Screening Phase: Up to 4 weeks Randomized Double-blind Phase: 24 weeks Open-label Extension Phase: 24 weeksFollow-up Phase: a phone call after Week 48
Each phase contains one or more study visits.
Read the detailed description
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder affecting 1% of the world's population. If not adequately controlled, it may lead to disability in up to 30% of patients within the first three years of disease onset [1] and can be associated with premature death. Recent research has suggested that the first event in the pathogenesis of RA is an antigen dependent activation of T-cells in an immunogenetically susceptible host. T-cells require two signals for activation, one involving the trimolecular complex (class II Major Histocompatibility Complex (MHC), antigen, T-cell receptor), and the other being co-stimulation of the CD28 (Cluster of Differentiation 28) molecule on T-cells by the B7 molecules (CD80 and CD86) on antigen presenting cells.
Hepatitis B virus (HBV) can cause chronic disease in 5% of immunocompetent adults and has a prevalence of over 350 million worldwide. It is a leading cause of chronic hepatitis, cirrhosis and hepatocellular cancer and accounts for one million deaths annually. In patients with chronic hepatitis B and RA, treatment options are limited. Traditional disease modifying anti-rheumatic drugs (DMARDs) are associated with hepatotoxicity and are contraindicated in chronic hepatitis. A recent retrospective analysis suggests that successful use of anti-tumor necrosis factor alpha (anti-TNF) agents may be possible in these patients but the authors do warn that these patients should be closely monitored and that fatal reactivation of hepatitis B is possible. Treatment with rituximab, a chimeric monoclonal antibody against B-cell protein CD20, is another option; however, the use of this medication in RA patients with chronic hepatitis B may also cause reactivation.
When RA patients with chronic hepatitis B were started on a Tumor Necrosis Factor (TNF) inhibitor or methotrexate (MTX), 2 of 5 HBsAg+ patients reactivated their hepatitis B, indicating a possible high rate of activation in these patients when not on hepatitis B treatment. Reactivation in this and another study occurred after 9-19 months of antirheumatic therapy. In RA patients with chronic Hepatitis B, entecavir appears to be effective at preventing reactivation.
There are no studies on the safety of abatacept in patients with RA and HBV. Adequate T-cell function is important to help cure or contain HBV infection. Our site has conducted a retrospective study that shows preliminary safety of abatacept in patients with RA and chronic Hepatitis B on antiviral therapy. The purpose of this study is to assess the safety and efficacy of abatacept in RA patients with chronic Hepatitis B in a pilot study in a randomized, controlled fashion.
- Conditions
- Rheumatoid Arthritis, Chronic Hepatitis B
- Being tested
- Abatacept, Placebo
- Keywords
- Rheumatoid Arthritis, Hepatitis B, Abatacept, Orencia, entecavir
- Medical subject headings
- Arthritis, Rheumatoid, Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
Also called Orencia
Abatacept Injection, 125 mg/Syringe (125 mg/mL), is a sterile solution for SC administration, which contains approximately 126 mg abatacept.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Abatacept Arm | Active comparator | This arm of study subjects will receive 125 mg subcutaneous abatacept during the 24 week double blind period. Receives: Drug: Abatacept |
| Placebo Arm | Placebo comparator | This arm of study patients will receive matching placebo injections during the 24 week double blind period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Serious Adverse Events
Adverse events will be assessed at timepoints specified in the protocol.
Measured: Every 4 weeks from Week 4 to Week 48
Number of Subjects with Hepatitis B Reactivation
Blood test for Hepatitis B Virus (HBV) DNA will be used.
Measured: Every 4 Weeks from Week 4 to Week 48
Secondary outcomes (12)
DAS28-ESR-4 Unit
Measured: Screening, Weeks 4, 8, 12, 24, 36, and 48
CDAI Unit
Measured: Screening, Weeks 4,8,12,24,36,48
TJC Count
Measured: Screening, Weeks 4,8,12,24,36,48
SJC Count
Measured: Screening, Weeks 4,8,12,24,36,48
Patient Global (Visual Analogue Scale)
Measured: Screening, Weeks 4,8,12,24,36,48
MD Global (Visual Analogue Scale)
Measured: Screening, Weeks 4,8,12,24,36,48
Pain (measured on a 5 point Likert scale)
Measured: Screening, Weeks 4,8,12,24,36,48
Global Assessment of Disease Activity (as measured on a 5 point Likert scale)
Measured: Screening, Weeks 4,8,12,24,36,48
HAQ-DI Units
Measured: Screening, Weeks 4,8,12,24,36,48
Fatigue (as assessed by FACIT-Fatigue Unit)
Measured: Screening, Weeks 4,8,12,24,36,48
Sleep as assessed by Medical Outcomes Study Sleep Instrument Unit
Measured: Screening, Weeks 4,8,12,24,36,48
ACR 20/50/70 Percentage
Measured: Screening, Weeks 4,8,12,24,36,48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2014 (estimated)
- Study startJul 2014
- Primary completion12 Jun 2018
- Study completion12 Jun 2018
Why it stopped: The study team did not enroll any patients due to difficulty with recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Suzanne Kafaja, M.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02053727
- Sponsor's protocol ID
- IM101329
- Other IDs
- 13-001279
- Acronym
- RA
- Status last verified
- Nov 2020
- First submitted
- 6 Nov 2013
- Last updated
- 16 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Evaluate Subcutaneous Abatacept vs Placebo in RA Patients With Hepatitis B on Entecavir Background- a Pilot, Double-blind, Placebo-controlled, Randomized, Controlled Trial.
- ClinicalTrials.gov ID
- NCT02053727
- Acronym / sponsor ID
- RA / IM101329
- Conditions
- Rheumatoid Arthritis, Chronic Hepatitis B
- Keywords
- Rheumatoid Arthritis, Hepatitis B, Abatacept, Orencia, entecavir
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study team did not enroll any patients due to difficulty with recruitment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- 12 Jun 2018 (actual)
- Study completion
- 12 Jun 2018 (actual)
- First posted
- 4 Feb 2014 (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.
The purpose of this study is to investigate whether the combination of abatacept along with entecavir (the study drugs) is safe and effective in treating symptoms related to rheumatoid arthritis (RA).
Abatacept, given in an intravenous (IV - injected into a vein) as well as subcutaneous form, is approved by the FDA for the treatment of RA. In this research, abatacept will be given by injection. A subcutaneous injection is an injection given under the skin.
Entecavir, to be taken by mouth, is approved by the FDA for the treatment of hepatitis B.
The study is divided into the following time periods:
Screening Phase: Up to 4 weeks Randomized Double-blind Phase: 24 weeks Open-label Extension Phase: 24 weeksFollow-up Phase: a phone call after Week 48
Each phase contains one or more study visits.
Detailed description
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder affecting 1% of the world's population. If not adequately controlled, it may lead to disability in up to 30% of patients within the first three years of disease onset [1] and can be associated with premature death. Recent research has suggested that the first event in the pathogenesis of RA is an antigen dependent activation of T-cells in an immunogenetically susceptible host. T-cells require two signals for activation, one involving the trimolecular complex (class II Major Histocompatibility Complex (MHC), antigen, T-cell receptor), and the other being co-stimulation of the CD28 (Cluster of Differentiation 28) molecule on T-cells by the B7 molecules (CD80 and CD86) on antigen presenting cells.
Hepatitis B virus (HBV) can cause chronic disease in 5% of immunocompetent adults and has a prevalence of over 350 million worldwide. It is a leading cause of chronic hepatitis, cirrhosis and hepatocellular cancer and accounts for one million deaths annually. In patients with chronic hepatitis B and RA, treatment options are limited. Traditional disease modifying anti-rheumatic drugs (DMARDs) are associated with hepatotoxicity and are contraindicated in chronic hepatitis. A recent retrospective analysis suggests that successful use of anti-tumor necrosis factor alpha (anti-TNF) agents may be possible in these patients but the authors do warn that these patients should be closely monitored and that fatal reactivation of hepatitis B is possible. Treatment with rituximab, a chimeric monoclonal antibody against B-cell protein CD20, is another option; however, the use of this medication in RA patients with chronic hepatitis B may also cause reactivation.
When RA patients with chronic hepatitis B were started on a Tumor Necrosis Factor (TNF) inhibitor or methotrexate (MTX), 2 of 5 HBsAg+ patients reactivated their hepatitis B, indicating a possible high rate of activation in these patients when not on hepatitis B treatment. Reactivation in this and another study occurred after 9-19 months of antirheumatic therapy. In RA patients with chronic Hepatitis B, entecavir appears to be effective at preventing reactivation.
There are no studies on the safety of abatacept in patients with RA and HBV. Adequate T-cell function is important to help cure or contain HBV infection. Our site has conducted a retrospective study that shows preliminary safety of abatacept in patients with RA and chronic Hepatitis B on antiviral therapy. The purpose of this study is to assess the safety and efficacy of abatacept in RA patients with chronic Hepatitis B in a pilot study in a randomized, controlled fashion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Abatacept Arm | Active comparator | Drug: AbataceptThis arm of study subjects will receive 125 mg subcutaneous abatacept during the 24 week double blind period. |
| Placebo Arm | Placebo comparator | Drug: PlaceboThis arm of study patients will receive matching placebo injections during the 24 week double blind period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of RA.
- Baseline CDAI >10 with TJC (Tender Joint Count) > 4 and SJC (Swollen Joint Count) > 2.
- Chronic Hepatitis B as defined by a history of patients with a HBsAg positive for at least 6 months with undetectable HBV DNA; or a history of patients with negative HBsAg and positive HBcAb or HBsAb, with undetectable HBV DNA.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening,) negative liver imaging as shown by ultrasound, computerized tomography or magnetic resonance imaging within 24 weeks of screening. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging and shown not to have HCC on CT or MRI before they can be enrolled.
- Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs (Non-Steroidal Anti-inflammatory Drugs) are permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to and including at baseline.
Key exclusion criteria (26 listed)
- Women who are pregnant or breastfeeding. Sexually active fertile men not using effective birth control if their partners are WOCBP (Women of Child Bearing Potential).
- Target Disease Exceptions
- Medical History and Concurrent Diseases
- Prohibited Treatments and/or Therapies
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 |
|---|---|---|
| AbataceptAlso: OrenciaAbatacept Injection, 125 mg/Syringe (125 mg/mL), is a sterile solution for SC administration, which contains approximately 126 mg abatacept. | Drug | Abatacept Arm |
| Placebo | Drug | Placebo Arm |
Primary outcome
Number of Participants with Serious Adverse Events
Time frame: Every 4 weeks from Week 4 to Week 48
Adverse events will be assessed at timepoints specified in the protocol.
Number of Subjects with Hepatitis B Reactivation
Time frame: Every 4 Weeks from Week 4 to Week 48
Blood test for Hepatitis B Virus (HBV) DNA will be used.
12 secondary outcomes
DAS28-ESR-4 Unit
Time frame: Screening, Weeks 4, 8, 12, 24, 36, and 48
CDAI Unit
Time frame: Screening, Weeks 4,8,12,24,36,48
TJC Count
Time frame: Screening, Weeks 4,8,12,24,36,48
SJC Count
Time frame: Screening, Weeks 4,8,12,24,36,48
Patient Global (Visual Analogue Scale)
Time frame: Screening, Weeks 4,8,12,24,36,48
MD Global (Visual Analogue Scale)
Time frame: Screening, Weeks 4,8,12,24,36,48
Pain (measured on a 5 point Likert scale)
Time frame: Screening, Weeks 4,8,12,24,36,48
Global Assessment of Disease Activity (as measured on a 5 point Likert scale)
Time frame: Screening, Weeks 4,8,12,24,36,48
HAQ-DI Units
Time frame: Screening, Weeks 4,8,12,24,36,48
Fatigue (as assessed by FACIT-Fatigue Unit)
Time frame: Screening, Weeks 4,8,12,24,36,48
Sleep as assessed by Medical Outcomes Study Sleep Instrument Unit
Time frame: Screening, Weeks 4,8,12,24,36,48
ACR 20/50/70 Percentage
Time frame: Screening, Weeks 4,8,12,24,36,48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2020.
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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.
Suzanne Kafaja, M.D. principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Abatacept in people with Rheumatoid Arthritis and Chronic Hepatitis B, run by University of California, Los Angeles at 1 site in United States.
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 6 inclusion and 26 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: withdrawn, as of the sponsor's last update on 16 Nov 2020. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of Participants with Serious Adverse Events (time frame: Every 4 weeks from Week 4 to Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Nov 2020.