Safety Study of Rituximab (Rituxan®) in Chronic Urticaria

This study has suspended participant recruitment.
(Full Clinical Hold)
Sponsor:
Collaborator:
Genentech
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00216762
First received: September 16, 2005
Last updated: February 28, 2008
Last verified: February 2008
  Purpose

This study is being done to find out if a drug called Rituxan (Rituximab) is safe and effective in treating people with chronic urticaria (hives) with persistent symptoms in spite of taking antihistamines.


Condition Intervention Phase
Urticaria
Drug: Rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Open Label Evaluation of the Safety and Efficacy of Rituximab in Patients With Chronic Urticaria (The Rituximab Urticaria Study - "RUSTY")

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Safety of Rituximab infusions in this patient population [ Time Frame: 1 year or time until reconstitution of B cells ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: January 2006
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Rituximab
    Rituxan ® 1000 mg IV x 2 infusions, 2 weeks apart
    Other Name: Rituxan ®
Detailed Description:

Rituximab (Rituxan®) is a recombinant chimeric monoclonal antibody that binds to a molecule (CD20) that is present on the surface of B lymphocytes. The product is approved for the treatment of non-Hodgkin's lymphoma and has been investigated for the treatment of a number of autoimmune diseases including rheumatoid arthritis (Edwards 2004) and lupus (Looney 2004, Leandro 2002). As in most rheumatoid arthritis studies, the medication will be administered in this study as a series of two intravenous infusions given 2 weeks apart.

Many cases of chronic urticaria (hives) are though to be driven by an autoimmune mechanism (Kaplan 2002, Grattan 2002). It is our hypothesis that by interfering with the autoimmune process, potentially by decreasing the levels of autoantibodies or by interfering with other mechanisms that cause basophil and mast cell activation, improvments in signs and symptoms will be seen.

Given the effectiveness demonstrated for Rituximab in other autoimmune conditions, we will conduct a pilot open label investigation of 15 patients with chronic urticaria to determine the safety and effectiveness of Rituximab in this disease. All patients will receive the medication; there will be no placebo group in this study. Rituximab is not currently indicated for the treatment of this condition however.

We will evaluate the safety of the Rituximab in 15 patients with urticaria as well as studies of antibody levels and cellular function. We will also evaluate clinical outcomes such as itch score, sleep disturbance, and quality of life. After receivng the Rituximab treatment, we will begin to taper antihistamines and other medications used to control urticaria symptoms.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Major Inclusion Criteria:

  • Chronic urticaria defined as symptoms >50% of the days or 3 days per week for more than 12 weeks
  • Previous requirement for sustained or recurrent use of corticosteroids OR requirement for immunomodulatory treatment for urticaria (eg hydroxychloroquine, sulfasalazine, dapsone, cyclosporine, IVIg, etc) OR ongoing symptoms for at least 6 months duration with failure to respond at least maximally approved dosages of 2 different antihistamine therapies
  • Chronic therapy with stable doses of antihistamines for at least 4 weeks. Patients may be taking more than one antihistamine or be taking combinations of antihistamines and leukotriene receptor antagonists
  • High baseline score for pruritis (at least 2 on a 3 point scale)
  • No underlying etiology clearly defined for urticaria
  • Evidence of underlying autoimmunity as evidenced by clinical and laboratory criteria
  • Concomitant use of hydroxychloroquine, sulfasalazine, or dapsone permitted if doses stable for at least 12 weeks
  • Negative serum pregnancy test (for women of child-bearing age)
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
  • No planned elective surgical procedures for at least 6 months

Major Exclusion Criteria:

  • Concomitant use of corticosteroids
  • Current use of immunosuppressive medication (cyclosporine, IVIg, methotrexate, cyclophosphamide). Any such medication will be discontinued for at least 6 weeks before screening.
  • Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
  • Receipt of a live vaccine within 4 weeks prior to randomization
  • Previous treatment with Rituximab (MabThera® / Rituxan®)
  • Prior antibody therapy
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • Known history of HIV seropositivity (testing will be performed at screening)
  • History of Hepatitis B and/or Hepatitis C (Hep BsAg and Hep C Ab will be obtained at screening)
  • History of recurrent significant infection or history of recurrent bacterial infections
  • Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds)
  • Any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
  • Known immunodeficiency syndrome, hypogammaglobulinemia, etc.
  • Systemic lupus erythematosus
  • Pregnancy (a negative serum pregnancy test will be performed for all women of childbearing potential within 7 days of treatment) or lactation
  • Malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Atopic dermatitis
  • Clinically relevant medical conditions (cardiovascular including poorly controlled hypertension or coronary artery disease, pulmonary, metabolic, renal, hepatic, psychiatric) or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Plans or need to receive live viral vaccination over course of the study (e.g. Flu-Mist TM)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00216762

Locations
United States, Maryland
Johns Hopkins University, Bayview Medical Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Genentech
Investigators
Principal Investigator: Clifton O. Bingham, III, MD Johns Hopkins University, Divisions of Rheumatology and Allergy and Clinical Immunology
  More Information

Publications:
Responsible Party: Clifton O. Bingham MD, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00216762     History of Changes
Other Study ID Numbers: NA_00000857
Study First Received: September 16, 2005
Last Updated: February 28, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
Urticaria
Hives

Additional relevant MeSH terms:
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014