Rheumatoid Arthritis Memory B Cells and Abatacept
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Abatacept; DMARDs
Intervention description: Abatacept for reconstitution and dilution prior to intravenous (IV) administration. Each single-use vial of Abatacept for injection provides 250-mg Abatacept, maltose (500 mg), monobasic sodium phosphate (17.2 mg), and sodium chloride (14.6 mg) for administration.; Patients will receive methotrexate or remain on pre-existing conventional synthetic disease-modifying anti-rheumatic drug (DMARD) if already prescribed.
Intervention MeSH terms: Abatacept
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Single-Open Label Study to Assess Changes in the Immune Profile in Response to Treatment with
      Intravenous Abatacept Adults with Rheumatoid Arthritis who are Naive to Biologic
      Disease-Modifying Antirheumatic Drugs
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed Written Informed Consent

             1. Subject is willing to participate in the study and has signed the informed consent.

          -  Target Population

               1. Men or women (not nursing or pregnant) over 18 years old who have active
                  Rheumatoid Arthritis, defined as symptoms of Rheumatoid Arthritis prior to
                  screening and have satisfied the American College of Rheumatology/ European
                  League Against Rheumatism 2010 criteria for the classification of Rheumatoid
                  Arthritis prior to signing t the informed consent.

               2. Subjects must have a Disease Activity Score 28-joint count C reactive protein
                  (CRP) or Clinical Disease Activity Index (CDAI) assessment at screening and have
                  at least 3 tender and at least 3 swollen joints (excluding distal interphalangeal
                  joints) at screening and at Day 1. Patients must have at least moderate disease
                  activity {CDAI>16); Disease Activity Score and C-reactive protein test (DAS28CRP
                  (>4.0 )].

               3. Subjects must be naive to biologic Disease-modifying antirheumatic drugs (DMARDs)

               4. Subjects must be naive to targeted synthetic DMARDs such as tofacitinib,
                  baricitinib, and investigational therapies for RA.

               5. Subjects receiving oral corticosteroids must be on a stable dose and at the
                  equivalent of 10 mg prednisone daily for at least 4 weeks. Subjects may not
                  receive an intravenous (IV), intramuscular (IM) or intra-arterial (IA)
                  administration of a corticosteroid within 4 weeks prior to screening visit or
                  initiation of therapy

               6. Patients with prior (including discontinued) therapy with Methotrexate and/or
                  Hydroxychloroquine are permitted as long as they meet other inclusionary
                  criteria.

               7. Subjects must have a DAS28CRP and Clinical Disease Activity Index (CDAI) at
                  screening and have at least 3 tender and at least 3 swollen joints (excluding
                  distal interphalangeal joints) at screening and at Day 1.

          -  Age and Reproductive Status

               1. Men and women, age's 18 years (or age of majority)

               2. Women of childbearing potential (WOCBP) must have a negative serum or urine

               3. pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within

               4. 24 hours prior to the start of study drug.

               5. Women must not be breastfeeding and must agree not to breastfeed during the study
                  and for 100 days thereafter

               6. WOCBP must agree to follow instructions for method(s) of contraception for the
                  duration of treatment with study drug plus 5 half-lives of study drug (70 days)
                  plus 30 days (duration of ovulatory cycle) for a total of 100 days post-treatment
                  completion.

               7. Males who are sexually active with WOCBP must agree to follow instructions for
                  method(s) of contraception for the duration of treatment with study drug, plus 5
                  half- lives of the study drug (70 days) plus 90 days (duration of sperm turnover)
                  for a total of 160 days post-treatment completion.

               8. Azoospermic males and WOCBP who are continuously not heterosexually active are
                  exempt from contraceptive requirements. However they must still undergo pregnancy
                  testing as described in this section. Investigators shall counsel WOCBP and male
                  subjects who are sexually active with WOCBP on the importance of pregnancy
                  prevention and the implications of an unexpected pregnancy.

               9. Investigators shall advise WOCBP and male subjects who are sexually active with
                  WOCBP on the use of highly effective methods of contraception. Highly effective
                  methods of contraception have a failure rate of < 1% when used consistently and
                  correctly.

              10. At a minimum, subjects must agree to use one highly effective method of
                  contraception as listed below.

          -  Highly effective methods of contraception

               1. Highly effective methods of contraception have a failure rate of < 1% when used
                  consistently and correctly. WOCBP and female partners of male subjects, who are
                  WOCBP, are expected to use one of the highly effective methods of contraception
                  listed below. Male subjects must inform their female partners who are WOCBP of
                  the contraceptive requirements of the protocol and are expected to adhere to
                  using contraception with their partner.

                    1. Progestogen only hormonal contraception associated with inhibition of
                       ovulation.

                    2. Hormonal methods of contraception including oral contraceptive pills
                       containing estrogen + progesterone, vaginal ring, injectables, implants and
                       intrauterine devices (IUDs) such as Mirena

                    3. Nonhormonal IUDs, such as ParaGard

                    4. Bilateral Tubal occlusion

                    5. Vasectomized partner with documented azoospermia 90 days after procedure

               2. Vasectomized partner is a highly effective birth control method provided that
                  partner is the sole sexual partner of the WOCBP trial participant and that the
                  vasectomized partner has received medical assessment of the surgical success.

               3. Intrauterine hormone-releasing system (IUS)

               4. Complete abstinence- Complete abstinence is defined as the complete avoidance of
                  heterosexual intercourse

                    1. complete abstinence is an acceptable form of contraception for all study
                       drugs and must be used throughout the duration of the study treatment (plus
                       5 half-lives of the investigational drug plus 30 days).

                    2. It is not necessary to use any other method of contraception when complete
                       abstinence is elected.

                    3. Subjects who choose complete abstinence must continue to have pregnancy
                       tests

                    4. Acceptable alternate methods of highly effective contraception must be
                       discussed in the event that the subject chooses to forego complete
                       abstinence.

                    5. The reliability of sexual abstinence needs to be evaluated in relation to
                       the duration of the clinical trial and the preferred and usual lifestyle of
                       the subject.

          -  Unacceptable methods of contraception

               1. Periodic abstinence (calendar, symptothermal, post-ovulation methods)

               2. Withdrawal (coitus interruptus)

               3. Spermicide only

               4. Lactation amenorrhea method (LAM)

        Exclusion Criteria:

          -  Target Disease Exceptions

               1. Subjects with autoimmune disease other than RA [e.g., psoriasis, systemic lupus
                  erythematosus (SLE), vasculitis, seronegative spondyloarthritis, Inflammatory
                  Bowel Disease, Sjogren's syndrome] or currently active fibromyalgia.

               2. Prior history of or current inflammatory joint disease other than RA (such as
                  psoriatic arthritis, gout, reactive arthritis, Lyme disease).

          -  Medical History and Concurrent Diseases 1.Subjects at risk for tuberculosis (TB)
             defined as follows:

               1. Current clinical, radiographic or laboratory evidence of active TB. Chest x-rays
                  (posterior anterior and lateral) obtained within the 3 months prior to obtaining
                  written informed consent will be permitted but the images must be available and
                  reviewed by the investigator. TB testing (IFN-gamma release assay or PPD)
                  performed in the past month prior to Screening will be accepted; however, a copy
                  of the report must be placed in the subject binder.

               2. A history of active TB

               3. Subjects with a positive TB screening test indicative of latent TB will not be
                  eligible for the study unless they:

               4. Have no evidence of current TB based on chest x-ray performed And they are
                  actively being treated for TB or the site has documentation of successful prior
                  treatment of latent TB. Treatment regimens should be dictated by local guidelines
                  as long as the treatment dose and duration meet or exceed local health authority
                  guidelines. 2.Subjects with recent acute infection defined as:

               1. Any acute infection within 60 days prior to randomization that required
                  hospitalization or treatment with parenteral antibiotics.

               2. Any acute infection within 30 days prior to randomization that required oral
                  antimicrobial or antiviral therapy. 3. Subjects with history of chronic or
                  recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and
                  bronchiectasis etc.). 4. Subjects with any history of infection of a joint
                  prosthesis or artificial joint.

                  5. Subjects who have a history of systemic fungal infections (such as
                  histoplasmosis, blastomycosis, or coccidiomycosis). 6. Subjects with history of
                  recurrent herpes zoster (more than 1 episode) or disseminated (more than 1
                  dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster
                  will be excluded. Symptoms of herpes zoster or herpes simplex must have resolved
                  more than 60 days prior to screening. 7. Subjects with history of Human
                  Immunodeficiency Virus (HIV) infection or who tested positive for HIV 8. Subjects
                  with history of primary immunodeficiency

               1. Subjects who have a present malignancy or previous malignancy within the last 5
                  years prior to screening (except documented history of cured non-metastatic
                  squamous or basal cell skin carcinoma or cervical carcinoma in situ). Subjects
                  who had a screening procedure that is suspicious for malignancy, and in whom the
                  possibility of malignancy cannot be reasonably excluded following additional
                  clinical, laboratory or other diagnostic evaluations. 10. Current clinical
                  findings or a history of a demyelinating disorder 11. New York Heart Association
                  (NYHA) Class III or IV heart failure 12. Any previous or current medical
                  conditions that are warnings against the use of TNF inhibitor agents. 13. Current
                  clinical findings of severe, progressive, or uncontrolled renal, hepatic,
                  hematological, gastrointestinal, pulmonary, psychiatric, cardiac, endocrine,
                  neurological, or cerebral disease including severe and uncontrolled infections,
                  such as sepsis and opportunistic infections. Concomitant medical conditions that,
                  in the opinion of the investigator, might place the subject at unacceptable risk
                  for participation in this study. 14. Subjects who have received any live vaccines
                  within 3 months of the study drug administration or are scheduled to receive live
                  vaccines during the study. Study subjects should not be administered a live virus
                  vaccine for a minimum of 3 months f following the last dose of study medication.
                  Subjects who are in close contact with others who have received a live vaccine
                  may be enrolled at the investigator's discretion. 15. Subjects who have undergone
                  a major surgical procedure within the 60 days prior to randomization. 16.
                  Subjects for whom 5 or more joints cannot be assessed for tenderness or swelling
                  (i.e. due to surgery, fusion, amputation, etc.). 17.Subjects who are prisoners,
                  or compulsory detained.