Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis

Status:	Active, not recruiting
Conditions:	Pulmonary
Therapuetic Areas:	Pulmonary / Respiratory Diseases
Healthy:	No
Age Range:	50 - 85
Updated:	2/21/2019
Start Date:	January 2014
End Date:	December 31, 2019

Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)

Recent research studies have suggested that proteins called antibodies that are produced by
the immune system might be involved in the lung damage of idiopathic pulmonary fibrosis
(IPF). Antibodies produced by the immune system normal help to fight infections by attacking
bacteria and viruses without harming our own tissues. In patients with IPF, there is evidence
that certain antibodies (called autoantibodies) attack the lung and contributes to the injury
and scarring that occurs in IPF. Our recent studies have found that many IPF patients appear
to have excessive autoantibody levels in blood and lungs that might make their disease worse.

Rituximab is a medication approved by the Food and Drug Administration (FDA) for the
treatment of autoantibody diseases such as rheumatoid arthritis. Rituximab works by
destroying B cells, a type of white blood cell, called a B-lymphocyte, which produce
autoantibodies. In this research study, rituximab will be given into a vein to reduce the
autoantibody levels that we believe might be contributing to the lung damage in IPF.

This study is being conducted to determine if rituximab provides beneficial effects for IPF
patients by decreasing further lung injury.

This is a double-blinded, Phase II trial in which 58 ambulatory IPF patients at any of four
medical centers (University of Pittsburgh, University of Chicago, Geisinger Medical Center,
and Temple University) will be randomized equally to 1. placebo or 2. two doses of rituximab
1 gm i.v., with a 14 day interval inbetween doses.

Subjects will be followed for 9 months.

Inclusion Criteria:

Ambulatory patients with a diagnosis of IPF, not established >5 years from the enrollment
date, that fulfills American Thoracic Society (ATS)/ETS Consensus Criteria.

Ability and willingness to give informed consent. Presence of autoantibodies against HEp-2
cells, the assay for the primary endpoint.

Age 50-85 y.o.

Exclusion Criteria:

Diagnoses of current infection, proven or suspected by participating physicians based upon
their clinical assessments.

Presence of active hepatitis B or C, or HIV infection. Presence of positive CONVENTIONAL
autoimmune serologic tests, e.g., Antinuclear Antibodies (ANA), Rheumatoid Factor (RF),
Anti-Ro, Anti-LA, Anti-Ribonucleoprotein Antibodies (RNP), Anti-Jo-1.

History of reaction to murine-derived products or any of the trial medications, or prior
exposures to human-murine chimeric antibodies.

Malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer,
defined as stage T1 or T2a with Prostate-Specific Antigen (PSA) less than 10 ng/dl.

Unwillingness to complete post-treatment surveillance for 9 months. Diagnosis of major
morbidities (aside from IPF) expected to interfere with subjects' study participation for 9
months.

Treatment for >5 days within the preceding month with >10 mg. prednisone (or equivalent
corticosteroid) or any treatment during the preceding month with a potent cellular
immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathioprine,
calcineurin inhibitors, etc.).

Uncontrolled diabetes or hypertension that preclude safe treatment with methylprednisolone.

Concurrent participation in other experimental trials.

Pregnancy or unwillingness to use contraception during the duration of the study among
female participants with child-bearing potential.

Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <70% of
predicted values.

We found this trial at

sites

Temple University

1801 N Broad St
Philadelphia, Pennsylvania 19122

(215) 204-7000