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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01969409
Recruitment Status : Completed
First Posted : October 25, 2013
Results First Posted : November 18, 2021
Last Update Posted : January 27, 2022
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Steven R. Duncan, MD, University of Alabama at Birmingham

Brief 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.

Condition or disease Intervention/treatment Phase
Ambulatory IPF Drug: Rituximab Drug: Placebo Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)
Actual Study Start Date : January 2014
Actual Primary Completion Date : January 31, 2019
Actual Study Completion Date : November 30, 2020

Arm Intervention/treatment
Placebo Comparator: Placebo
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Drug: 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.
Other Name: Placebo (D5W) i.v.

Experimental: Rituximab
Rituximab i.v. given on two occasions, with 14 days between doses.
Drug: Rituximab
i.v. rituximab given on two occasions 14 days apart.

Primary Outcome Measures :
  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 Outcome Measures :
  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.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01969409

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnestoa
Minneapolis, Minnesota, United States, 55455
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822
Temple University
Philadelphia, Pennsylvania, United States, 19122
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
University of Alabama at Birmingham
National Institutes of Health (NIH)
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Principal Investigator: Steven R Duncan, MD University of Alabama at Birmingham
  Study Documents (Full-Text)

Documents provided by Steven R. Duncan, MD, University of Alabama at Birmingham:
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Responsible Party: Steven R. Duncan, MD, Priniciple Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01969409    
Other Study ID Numbers: HL119960
First Posted: October 25, 2013    Key Record Dates
Results First Posted: November 18, 2021
Last Update Posted: January 27, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Steven R. Duncan, MD, University of Alabama at Birmingham:
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents