HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II

A Double-blind, Randomized, Placebo Controlled, Dose Escalation, Multi-centerphase I/II Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20antibody, in Patients With Active Rheumatoid Arthritis Who Have Previously Failedone or More Disease Modifying Anti-rheumatic Drugs

The purpose of this trial is primarily to investigate the safety profile of HuMax-CD20 in patients with active RA. Furthermore, the trial is designed to identify the dose levels to be used in future trials (based on evaluations of safety, pharmacokinetics and ACR and DAS responses).

This trial consists of a double-blind, placebo controlled, dose escalation part with randomization to trial treatment within each of three sequential cohorts (Part A), and a parallel group part with randomization into one of four treatment arms (Part B). Patients in Parts A and B will receive two infusions of either HuMax-CD20 (300 mg, 700 mg, or 1000 mg) or placebo and will be followed for safety, efficacy, and pharmacokinetic measurements for 24 weeks. Hereafter patients will be followed every 12 weeks until B-cells (CD19+ cells) have returned to baseline levels. For patients in Part B, the follow-up visits at 36 and 48 weeks after initial trial treatment (Follow-up Visits 1 and 2) will include additional measurements of safety and efficacy.

Inclusion Criteria:

• Age ≥ 18 years
• Active rheumatoid arthritis according to the American College of Rheumatology of at least six months duration with six or more swollen and six or more tender joints (of 28 joints) and Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/h and/or C-Reactive Protein (CRP) ≥ 10 mg/L (1 mg/dL).
• Treatment failure to one or more DMARDs.
• Treatment with methotrexate (7.5-25 mg/wk) for at least 12 weeks and at a stable dose for at least 4 weeks prior to planned start of trial treatment.

Exclusion Criteria:

• Use of DMARDs other than methotrexate.
• Current or previous (within four weeks of screening) participation in any other clinical trial.
• Previous exposure to other biological products within 4 weeks prior to planned start of trial treatment, and/or exposure to anti-CD20 antibodies within two years before screening for this trial.
• Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial.
• Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy.
• Past or current malignancy, except for resected cervical carcinoma Stage 1B or less, non-invasive basal cell and squamous cell skin carcinoma, malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years.
• Chronic or current infectious disease including known or suspected positive serology for HIV, hepatitis B, or hepatitis C.
• Clinically significant cardiac disease, or history of significant cerebrovascular disease.
• Significant concurrent, uncontrolled medical condition including, but not limited to: renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
• Breast feeding women, women with a positive pregnancy test at screening, or women of childbearing potential not willing to use adequate contraception during the trial.