A Study of the Pharmacokinetics and Safety of MK-8808 (MK-8808-002)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: MK-8808; MabThera® (rituximab); Methotrexate; Rituxan® (rituximab); Methylprednisolone; Acetaminophen; Loratadine
Intervention description: MK-8808 500 mg/m^2 administered by IV on Day 1 and Day 15 or MK-8808 1000 mg administered by IV at Week 54 and Week 56; MabThera® 500 mg/m^2 or 1000 mg administered by IV on Day 1 and Day 15; Methotrexate 10-25 mg administered orally, SC, or IM as a weekly stable dose; Rituxan® 1000 mg administered by IV on Day 1 and Day 15; Methylprednisolone 100 mg administered IV before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions; Acetaminophen 1000 to 1350 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions; Loratidine 10 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
Intervention MeSH terms: Acetaminophen; Loratadine; Methylprednisolone; Rituximab; Methotrexate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Rheumatoid arthritis; RA; Rituximab; Rituxan; MabThera; Methotrexate; Rheumatrex; Trexall; MK-8808

Summary:

      This is a study of the overall safety, tolerability, and pharmacokinetics (PK) of MK-8808
      versus rituximab (MabThera® and Rituxan®) in participants with moderate to severe RA with an
      inadequate response or intolerance to methotrexate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female participants of reproductive potential must demonstrate a serum β-human
             chorionic gonadotropin (hCG) level consistent with the nongravid state at the
             pre-study (screening) visit, and a negative urine pregnancy test within 24 hours prior
             to all doses and agree to use (and/or have their partner use) two acceptable methods
             of birth control beginning at least 2 weeks prior to administration of the first dose
             of study drug, throughout the study (including washout intervals between treatment
             periods/panels) and until at least 12 months after administration of the last dose of
             study drug in the last treatment period

          -  The participant has a Body Mass Index (BMI) ≤35 kg/m^2 at the prestudy (screening)
             visit

          -  For Part A Only: The participant has a body surface are (BSA) ≤2.0 m^2 at the prestudy
             (screening) visit.

          -  Has satisfied at least 4 of 7 American Rheumatology Association (ARA) 1987 revised
             criteria for the diagnosis of RA

          -  Is American College of Rheumatology (ACR) Functional Class I, II, or III

          -  Had a diagnosis of RA made at least 6 months prior to the prestudy (screening) visit,
             was ≥ 16 years of age when diagnosed, and has active disease

          -  Is on a stable oral, IM, or SC dose of methotrexate and is continuing to take
             methotrexate

          -  Has an inadequate response or intolerance to at least one disease-modifying
             antirheumatic drug (DMARD)

          -  For Part A: Participant is either naïve to biological therapy for RA or has had an
             inadequate response to previous or current treatment with an anti-tumor necrosis
             factor (TNF) treatment (patient could have failed up to three anti-TNF agents
             treatments) or participant has had intolerance up to three anti-TNF treatments.

          -  For Part B: Participant has had an inadequate response to previous or current
             treatment with an anti-TNF treatment (patient could have failed up to three anti-TNF
             agents treatments) or participant has had intolerance up to three anti-TNF treatments

          -  Participant has no clinically significant abnormality on electrocardiogram performed
             at the prestudy (screening) visit and/or prior to administration of the initial dose
             of study drug

          -  For Part B Only: Participant is positive for rheumatoid factor (RF) or, if negative
             for RF, is positive for anti-CCP at screening visit

          -  For Part C Only: Participant must have completed the first 52 weeks of treatment in
             the base study

          -  For Part C Only: Participant achieved a minimum 20% response from baseline on the
             American College of Rheumatology (ACR) Responder Index (ACR20) at Visit 19 (last visit
             for the base study)

        Exclusion Criteria:

          -  Mentally or legally incapacitated, has significant emotional problems at the time of
             the prestudy (screening) visit or during the conduct of the study or has a history of
             a clinically significant psychiatric disorder over the last 5 years

          -  Creatinine clearance of ≤ 80 mL/min

          -  History of stroke, chronic seizures or major neurological disorder

          -  History of neoplastic disease, except treated basal cell carcinoma or carcinoma in
             situ of the cervix or other malignancies which have been successfully treated ≥ 5
             years

          -  History of leukemia, lymphoma, malignant melanoma, or myeloproliferative disease
             regardless of the time since treatment

          -  History of coronary artery disease, congestive heart failure (New York Heart
             Association Class I-IV), or a history of clinically significant arrhythmia (including
             any history of atrial fibrillation, atrial flutter, or any sustained ventricular
             arrhythmia)

          -  Hypersensitivity or allergy to rituximab or any of the excipients of MK-8808 or
             rituximab (MabThera® or Rituxan® )

          -  History of a rheumatic autoimmune disease other than RA (e.g. systemic lupus
             erythematosus (SLE), polymyositis, etc.)

          -  Severe active infection of any type or history of a medically serious infection as
             defined by a history of treatment requiring hospitalization, long term IV outpatient
             treatment for systemic bacterial, viral or fungal infection, use of IV antibiotics
             within 30-days of screening, or use of antibiotic therapy three or more times in the
             last six months prior to screening

          -  History of opportunistic infection

          -  Active-virus vaccination within 4 weeks

          -  Active tuberculosis with or without adequate treatment, history of latent tuberculosis
             without written confirmation from health care provider of adequate prophylaxis or any
             evidence of tuberculosis on a chest X-ray performed within 3 months of dosing

          -  Chronic hepatitis B or hepatitis C infection or has human immunodeficiency virus (HIV)
             infection

          -  Previously treated with rituximab (MabThera® or Rituxan®) or any investigational
             anti-CD20 antibody

          -  Active use or planned use of a prohibited DMARD during the course of study
             participation, and/or insufficient washout from a prohibited DMARD at the time of the
             planned first dose of MK-8808/rituximab (MabThera® or Rituxan®)

          -  Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
             weeks

          -  Participated in another investigational study with length of time within at least 5
             half-lives of the previous investigational study drug

          -  Pregnant or breastfeeding or expecting to conceive

          -  Allergy to murine proteins

          -  Allergy or sensitivity to components of the drug vial or any of the materials used for
             infusion