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

NCT ID: NCT00291928

Last Updated: 2012-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2007-09-30

Brief Summary

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).

Detailed Description

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.

Conditions

Arthritis, Rheumatoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dose ranging

A double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A),

Group Type: PLACEBO_COMPARATOR

Part A

Intervention Type: DRUG

Part A Cohort 1: HuMax-CD20 300 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 2: HuMax-CD20 700 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 3: HuMax-CD20 1000 mg at Days 0 and 14 or Placebo at Days 0 and 14

Parallel Arm RCT

a parallel group part with randomization into one of 4 treatment arms (Part B).

Group Type: PLACEBO_COMPARATOR

Part B

Intervention Type: DRUG

Part B Group 1: HuMax-CD20 300 mg at Days 0 and 14 Group 2: HuMax-CD20 700 mg at Days 0 and 14 Group 3: HuMax-CD20 1000 mg at Days 0 and 14 Group 4: Placebo at Days 0 and 14

Interventions

Part A

Part A Cohort 1: HuMax-CD20 300 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 2: HuMax-CD20 700 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 3: HuMax-CD20 1000 mg at Days 0 and 14 or Placebo at Days 0 and 14

Intervention Type: DRUG

Part B

Part B Group 1: HuMax-CD20 300 mg at Days 0 and 14 Group 2: HuMax-CD20 700 mg at Days 0 and 14 Group 3: HuMax-CD20 1000 mg at Days 0 and 14 Group 4: Placebo at Days 0 and 14

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Countries

Denmark; Finland; France; Hungary; Poland; United Kingdom; United States

References

Struemper H, Sale M, Patel BR, Ostergaard M, Osterborg A, Wierda WG, Hagenbeek A, Coiffier B, Jewell RC. Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis. J Clin Pharmacol. 2014 Jul;54(7):818-27. doi: 10.1002/jcph.268. Epub 2014 Jan 28.

Reference Type: DERIVED

PMID: 24443277 (View on PubMed)

Ostergaard M, Baslund B, Rigby W, Rojkovich B, Jorgensen C, Dawes PT, Wiell C, Wallace DJ, Tamer SC, Kastberg H, Petersen J, Sierakowski S. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum. 2010 Aug;62(8):2227-38. doi: 10.1002/art.27524.

Reference Type: DERIVED

PMID: 20506254 (View on PubMed)

Other Identifiers

HX-CD20-403

Identifier Type: OTHER

Identifier Source: secondary_id

112657

Identifier Type: -

Identifier Source: org_study_id