Beryllium Infliximab Study: Clinical Interventional Trial

NCT00111917 | Terminated Phase 1 Results DMC

• 2 other identifiers: NJ2021UL1RR025780
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Berylliosis; Beryllium Disease

Keywords

Chronic Beryllium Disease; Berylliosis; Beryllium Disease; CBD; Infliximab

Outcome Measures

Primary Outcomes (1)

• A-a Gradient at End Exercise

  change in end-exercise A-a gradient

  after 28 week follow-up. The Alveolar-arterial gradient (A-a gradient), is a measure of the difference between the alveolar partial pressure (A) of oxygen and the arterial (a) partial pressure of oxygen

Study Arms (2)

Infliximab

EXPERIMENTAL

infusion: 3:1 infliximab:placebo ratio administered at 0, 2, 6, 12, 18 and 24 weeks.

Drug: Infliximab

Placebo

PLACEBO COMPARATOR

infusion: 3:1 infliximab:placebo ratio administered at 0, 2, 6, 12, 18 and 24 weeks.

Other: Placebo

Interventions

Infliximab DRUG

anti-TNF

Also known as: Remicade

Infliximab

Placebo OTHER

Placebo infusion

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maier, Lisa, M.D.: lead
• Centocor, Inc.: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80401, United States

Location

Related Publications (1)

• Maier LA, Barkes BQ, Mroz M, Rossman MD, Barnard J, Gillespie M, Martin A, Mack DG, Silveira L, Sawyer RT, Newman LS, Fontenot AP. Infliximab therapy modulates an antigen-specific immune response in chronic beryllium disease. Respir Med. 2012 Dec;106(12):1810-3. doi: 10.1016/j.rmed.2012.08.014. Epub 2012 Sep 11. No abstract available.

  PMID: 22974830 DERIVED

MeSH Terms

Conditions

Berylliosis

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Pneumoconiosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Occupational Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Although our goal was 20 CBD subjects, only 11 subjects were enrolled, 8:3 in the infliximab:placebo treatment arms as the study was stopped by the sponsor due to slow recruitment.

Results Point of Contact

• Title: Lisa Maier, MD
• Organization: National Jewish Health

maierl@njhealth.org

303-398-1983

Study Officials

• Lisa A Maier, MD,MSPH

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2005
• First Posted: May 27, 2005
• Study Start: February 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: June 2, 2016
• Results First Posted: September 25, 2014

Record last verified: 2016-03

Locations

US (1)