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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01969409
Other study ID # HL119960
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date January 2014
Est. completion date November 30, 2020

Study information

Verified date January 2022
Source University of Alabama at Birmingham
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 58
Est. completion date November 30, 2020
Est. primary completion date January 31, 2019
Accepts healthy volunteers No
Gender All
Age group 50 Years to 85 Years
Eligibility Inclusion Criteria: Ambulatory patients with a diagnosis of IPF, not established >5 years from the enrollment date, that fulfills American Thoracic Society (ATS)/European Thoracic Society (ETS) Consensus Criteria. Ability and willingness to give informed consent. Presence of autoantibodies against Hepatoma-2 (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.

Study Design


Intervention

Drug:
Rituximab
i.v. rituximab given on two occasions 14 days apart.
Placebo
Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.

Locations

Country Name City State
United States University of Alabama at Birmingham Birmingham Alabama
United States Brigham and Women's Hospital Boston Massachusetts
United States Medical University of South Carolina Charleston South Carolina
United States Geisinger Medical Center Danville Pennsylvania
United States University of Minnestoa Minneapolis Minnesota
United States Temple University Philadelphia Pennsylvania
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania

Sponsors (2)

Lead Sponsor Collaborator
University of Alabama at Birmingham National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Autoantibodies to Human Epidermoid (HEp)-2 Cells Titers of anti-HEp-2 autoantibodies, by indirect immunofluorescence assays (IFA) over 9 months, month 9 reported. Titers represent the highest dilution of patient plasma wherein the autoantibodies can be detected. Higher titers denote greater autoantibody concentrations. baseline to 9 months
Secondary Changes in Anti-Heat Shock Protein 70 (HSP70) Autoantibodies Changes of anti-HSP70 plasma concentrations as determined by ELISA, month 9 reported. The result is expressed as optical density (OD) units. The greater the number; the more autoantibody. baseline to 9 months
Secondary Changes in Forced Vital Capacity (FVC) FVC values over the observation period will be measured by spirometry, month 9 reported. baseline thru 9 months
Secondary Number of Adverse Events (AE) AE in the two treatment arms will be compared. Serious adverse events, as defined by national toxicity scale. during the 9 months of observation
Secondary Number of Acute Exacerbations The number of acute exacerbations, defined using consensus criteria (new/worsened hypoxemia and dyspnea, with characteristic radiographic changes within the last 30 days). during the study duration of 9 months
Secondary Absolute Survival Percentage Absolute survival in the two arms calculated by actuarial methods (Kaplan-Meier). These result in percent survival denoted as means and +/- standard error (these are detailed in the outcome table below). during 9 months of observation
Secondary Transplant-Free Survival Actuarial transplant-free survival in the two arms, calculated by actuarial methods (Kaplan-Meier).
These result in percent survival denoted as means and +/- standard error (these are detailed in the outcome table below).
during 9 months of observation
Secondary Hospitalizations The number of hospitalizations in the two arms will be compared. during 9 months of observation