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

Sponsor:	GlaxoSmithKline
Information provided by (Responsible Party):	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00291928

Purpose

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).

Condition	Intervention	Phase
Arthritis, Rheumatoid	Drug: Part A Drug: Part B	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Ofatumumab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 36 & 48 weeks after initiation of treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment:	201
Study Start Date:	February 2005
Study Completion Date:	September 2007
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Dose ranging A double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A),	Drug: 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
Placebo Comparator: Parallel Arm RCT a parallel group part with randomization into one of 4 treatment arms (Part B).	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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00291928

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Østergaard 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.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00291928 History of Changes
Other Study ID Numbers:	112657, HX-CD20-403
Study First Received:	February 14, 2006
Last Updated:	March 8, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases

Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2012