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

November 8, 2012 updated by: GlaxoSmithKline

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

201

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
Time Frame: 24 weeks
24 weeks
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
24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
24 weeks
To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis
Time Frame: 24 weeks
24 weeks
To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20
Time Frame: 24 weeks
24 weeks
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
48 weeks
To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis
Time Frame: 24 weeks
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

September 1, 2007

Study Registration Dates

First Submitted

February 14, 2006

First Submitted That Met QC Criteria

February 14, 2006

First Posted (Estimate)

February 15, 2006

Study Record Updates

Last Update Posted (Estimate)

November 12, 2012

Last Update Submitted That Met QC Criteria

November 8, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 112657
  • HX-CD20-403 (Other Identifier: GENMAB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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