| Eligibility |
Inclusion Criteria:
- Patient is male or female, 18 to 80 years of age, inclusive, at time of Screening.
- Patients diagnosed with RA for at least 4 months and currently classified according to
the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism
classification criteria for RA (score = 6/10).
- Patients with moderate to severe active RA as defined by = 6 swollen (out of 66) and =
6 tender (out of 68) joint counts and abnormal elevation of C-Reactive Protein (CRP)
(= 6 mg/L) and fulfills one of the two criteria at screening: a) Positive rheumatoid
factor b) Evidence of one joint erosion on radiological assessment of the hands,
wrists, or feet at Screening.
- Disease Activity Score in 28 joints C-reactive protein (DAS28 CRP) score of = 3.2 at
Screening.
- Eligible to receive treatment on ambulatory care.
- RA functional Class I, II, or III.
- Patients must be taking methotrexate (MTX) orally for = 12 weeks at a stable dose of =
12.5 mg in the last 4 weeks prior to screening and plan to remain on stable dose
throughout the study. Patients who are on methotrexate for a minimum of 10 mg per week
will be eligible if there is documented intolerance to further dose escalation.
- If patients are using oral corticosteroids, they must have been on a stable dose of up
to 10 mg/day prednisolone or equivalent, for = 4 weeks prior to first study dose.
- Naive to adalimumab. Prior treatment with one biologic is allowed.
- Patient has a negative QuantiFERON test for tuberculosis (TB) during Screening.
- Note: Patients with a positive and indeterminate QuantiFERON test are allowed if they
have all of the following:
- No evidence of active TB on chest radiograph within 3 months prior to the first dose
of study drug.
- Documented history of adequate prophylaxis initiation prior to receiving study drug in
accordance with local recommendations.
- No known exposure to active TB after most recent prophylaxis.
- Asymptomatic at Screening and baseline (BL).
- Patients who test positive for TB must be treated for 1 month prior to taking part in
the study. Investigators should check with the medical monitor before enrolling
patients receiving active treatment for TB.
- Investigators should check with the medical monitor before enrolling such patients.
- Sexually active women of childbearing potential must agree to use highly effective
contraception (hormonal contraception pills or injection or implants, sterilization,
and abstinence) for the duration of the study and until 3 months after the last dose
of the study drug.
- Male patients must agree to use contraception for the duration of the study and agree
not to donate sperm during and for 3 months after the last dose of study drug.
- Evidence of a personally signed and dated informed consent document indicating that
the patient (or a legal representative) has been informed of all pertinent aspects of
the study.
- Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
Exclusion Criteria:
- Patients with previous experience of self-administering medications using an
autoinjector or pen (either marketed or investigational).
- Patients who upon initial training are determined not to be acceptable candidates for
self-administration.
- RA with significant secondary involvement of any systemic organ (including but not
limited to vasculitis, pulmonary fibrosis).
- Prior treatment with more than 1 biologic or 1 protein kinase inhibitor DMARD for RA.
- Previous receipt of HUMIRA® (adalimumab) or a biosimilar of adalimumab.
- Prior treatment with TNF inhibitors for RA with lack of efficacy as per clinical
judgment.
- Treatment with DMARD other than MTX within 4 weeks prior to screening (8 weeks in case
of leflunomide and azathioprine).
- History of or current inflammatory joint disease other than RA (eg, gout, reactive
arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or
other systemic autoimmune disorder (eg, systemic lupus erythematosus, inflammatory
bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, or
any overlap syndrome).
- Any surgical procedure, including bone/joint surgery/synovectomy (including joint
fusion or replacement), within 8 weeks prior to informed consent or planned during the
study, or history of infected joint prosthesis within 5 years.
- Pregnancy or breast feeding.
- Significant cardiac (eg, New York Heart Association = III) or pulmonary disease
(including obstructive pulmonary disease).
- Evidence of clinically significant uncontrolled concomitant disease (cardiac, renal,
hepatic, pulmonary, metabolic, or gastro-intestinal) which in the Investigator's or
medical monitor's opinion would preclude patient participation.
- Primary or secondary immunodeficiency (history of or currently active), including
known history of human immunodeficiency virus (HIV) infection.
- Patient has an active and serious infection or history of infections as follows:
- Any active infection:
- For which non-systemic anti-infectives were used within 4 weeks prior to Day 0 (BL).
Note: patients receiving topical antibiotics for facial acne do not need to be
excluded.
- Which required hospitalization or systemic anti-infective within 8 weeks prior to Day
0 (BL).
- Recurrent or chronic infections or other active infection that, in the opinion of the
Investigator or designee, might cause this study to be detrimental to the patient.
- Invasive fungal infection or mycobacterial infection.
- Opportunistic infections, such as listeriosis, legionellosis, or pneumocystis.
- Patient has a history of malignancy within 5 years except for adequately treated
cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast
ductal carcinoma.
- Any neurological (congenital or acquired), vascular or systemic disorder which could
affect any of the efficacy assessments.
- Has evidence (as assessed by the Investigator or designee using good clinical
judgment) of active substance abuse (alcohol or drugs) within 6 months of Screening
that may impact patient's ability to participate in the study.
- Patient has a known history of allergic reactions attributed to compounds of similar
chemical or biologic composition to active substance or to any of the excipients of
Humira or AVT02.
- Treatment with any investigational agent 90 days prior to informed consent or 5
halflives of the investigational drug (whichever is longer) and unwilling to undergo
washout.
- Previous treatment with any cell-depleting therapies, excluding cyclosporine or MTX,
within previous 12 months, including investigational agents. Patients who have
received cyclosporine, leflunomide, cyclophosphamide, or azathioprine in the past must
have recovered from all drugrelated adverse events (AEs).
- Patient has received live or attenuated vaccines during the 4 weeks prior to Day 0
(BL) or has the intention of receiving a live or attenuated vaccine at any time during
the study.
- Intra-articular or parenteral glucocorticoids within 4 weeks prior to informed
consent.
- Positive tests for HIV, hepatitis B surface antigen, or hepatitis C serology.
- Hemoglobin < 8.0 g/dL.
- Absolute Neutrophil Count < 1500 cells/mm3.
- Absolute Lymphocyte Count < 800 cells/mm3.
- Platelet count < 100 000 mm3.
- Aspartate aminotransferase and/or alanine aminotransferase that is persistently = 2 ×
the upper limit of normal. (Persistently indicates at least on 2 occasions separated
by a number of days).
- Creatinine clearance < 50 mL/min (Cockcroft-Gault formula).
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