Beryllium Infliximab Study: Clinical Interventional Trial

• Status: Terminated
• Trial end date: 2009-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this research study is to test the clinical effectiveness of a drug called infliximab (Remicade) in chronic beryllium disease (CBD). This drug may reduce tumor necrosis factor-alpha (TNF-a), which is associated with more severe disease and inflammation in the lung. Receiving infliximab may help with symptoms, and may improve clinical testing data normally ordered by your doctor, such as breathing tests. Baseline and follow-up testing will look for improvements in breathing tests (pulmonary function testing), exchange of oxygen in the lungs (exercise test), chest x ray, and lung inflammation.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Maier, Lisa, M.D.
• Collaborators: Centocor, Inc.; National Center for Research Resources (NCRR)
• Treatments: Infliximab

Criteria

Inclusion Criteria:

• Ages 18-80.

• Noncaseating granulomas and/or mononuclear cell infiltrates demonstrated on transbronchial lung biopsy.

• Abnormal blood and/or BAL BeLPT results.

• Current treatment with prednisone and/or methotrexate specifically for CBD and not any other condition, at any range of dosage, for at least 6 months prior to enrollment, and on a stable dosage for at least 1 month prior to first infusion.

• Moderate CBD severity, such that participants can safely undergo bronchoscopy with BAL including PaO2 >= 50 mmHg on room air (at Denver altitude of 5,280 ft).

• Availability to come back to National Jewish Medical and Research Center for infusions, evaluations, and follow-ups.

• Capable of providing informed consent.

• Willing and able to adhere to the study visit schedule and other protocol-specified procedures.

Exclusion Criteria:

• Positive tuberculosis (TB) skin test upon screening: An intradermal tuberculin skin test must be performed within 1 month prior to the first administration of study agent.

• Any evidence of TB.

• Considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules.

• Positive pregnancy test.

• Women who are pregnant, nursing, or planning pregnancy within one year after screening

• Contraindications to bronchoscopy and BAL such as bleeding diathesis, PaO2 <50 mmHg on room air, evidence of acute infection, hemodynamic instability with labile blood pressure, either <90/60 or >160/110, untreated coronary artery disease, or other medical reason for which a subject will not be able to safely undergo bronchoscopy.

• Positive cultures from prior BAL indicating mycobacterial or fungal infection.

• Positive special stains for acid fast bacilli (AFB) or fungi on prior lung biopsies.

• Known atypical mycobacterium infection.

• Clinical evidence of active infection at time of enrollment.

• Serious acute infections (e.g., viral hepatitis, pneumonia or pyelonephritis) in the previous 3 months.

• Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.

• Documented HIV infection.

• Positive serology for active hepatitis B or C. A positive result will indicate the need for referral to a consultant Hepatologist for further investigation and support.

• Use of any investigational drug within 1 month prior to screening or within 5 half lives of the investigational agent, whichever is longer.

• Treatment with any other therapeutic agent targeted at reducing TNF-a (e.g. pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening.

• Prior use of Enbrel® or Humera®.

• Previous administration of infliximab.

• Known allergy to murine (mouse) products.

• Have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis).

• Any history of congestive heart failure, severe right sided heart failure, or cor pulmonale.

• Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening).

• Major surgery in the previous 3 months.

• Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence).

• History of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or perioaortic areas), or splenomegaly.

• Known recent substance abuse (drug or alcohol).

• Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.