Skip to main content
OpenTrials
Completed

NCT Number: NCT01969409

Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Ambulatory IPF Fibrosis Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Rituximab

Drug

i.v. rituximab given on two occasions 14 days apart.

Placebo

Drug

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.

Other names: Placebo (D5W) i.v.

Primary outcomes

  1. Autoantibodies to Human Epidermoid (HEp)-2 Cells

    Time frame: baseline to 9 months

    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.

Secondary outcomes

  1. Changes in Anti-Heat Shock Protein 70 (HSP70) Autoantibodies

    Time frame: baseline to 9 months

    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.

  2. Changes in Forced Vital Capacity (FVC)

    Time frame: baseline thru 9 months

    FVC values over the observation period will be measured by spirometry, month 9 reported.

  3. Number of Adverse Events (AE)

    Time frame: during the 9 months of observation

    AE in the two treatment arms will be compared. Serious adverse events, as defined by national toxicity scale.

  4. Number of Acute Exacerbations

    Time frame: during the study duration of 9 months

    The number of acute exacerbations, defined using consensus criteria (new/worsened hypoxemia and dyspnea, with characteristic radiographic changes within the last 30 days).

  5. Absolute Survival Percentage

    Time frame: during 9 months of observation

    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).

  6. Transplant-Free Survival

    Time frame: during 9 months of observation

    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).

  7. Hospitalizations

    Time frame: during 9 months of observation

    The number of hospitalizations in the two arms will be compared.

Sponsors and collaborators

Lead sponsor

University of Alabama at Birmingham

Other

Collaborators

  • National Institutes of Health (NIH)

Registry information

Official study title

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

Acronym: ART-IPF

Important dates

Study start
2014
Primary completion
2019
Study completion
2020
First posted
Oct 25, 2013
Registry last updated
Aug 21, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.