Back to resultsAutoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)
Primary Purpose
Ambulatory IPF
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ambulatory IPF focused on measuring Lung, Fibrosis
Eligibility Criteria
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.
Sites / Locations
- University of Alabama at Birmingham
- Brigham and Women's Hospital
- University of Minnestoa
- Geisinger Medical Center
- Temple University
- University of Pittsburgh Medical Center
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Rituximab
Arm Description
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Rituximab i.v. given on two occasions, with 14 days between doses.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Changes in Forced Vital Capacity (FVC)
FVC values over the observation period will be measured by spirometry, month 9 reported.
Number of Adverse Events (AE)
AE in the two treatment arms will be compared. Serious adverse events, as defined by national toxicity scale.
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).
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).
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).
Hospitalizations
The number of hospitalizations in the two arms will be compared.
Full Information
NCT ID
NCT01969409
First Posted
October 17, 2013
Last Updated
January 20, 2022
Sponsor
University of Alabama at Birmingham
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT01969409
Brief Title
Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis
Acronym
ART-IPF
Official Title
Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
January 2014 (Actual)
Primary Completion Date
January 31, 2019 (Actual)
Study Completion Date
November 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
National Institutes of Health (NIH)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ambulatory IPF
Keywords
Lung, Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Rituximab i.v. given on two occasions, with 14 days between doses.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
i.v. rituximab given on two occasions 14 days apart.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (D5W) i.v.
Intervention Description
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.
Primary Outcome Measure Information:
Title
Autoantibodies to Human Epidermoid (HEp)-2 Cells
Description
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.
Time Frame
baseline to 9 months
Secondary Outcome Measure Information:
Title
Changes in Anti-Heat Shock Protein 70 (HSP70) Autoantibodies
Description
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.
Time Frame
baseline to 9 months
Title
Changes in Forced Vital Capacity (FVC)
Description
FVC values over the observation period will be measured by spirometry, month 9 reported.
Time Frame
baseline thru 9 months
Title
Number of Adverse Events (AE)
Description
AE in the two treatment arms will be compared. Serious adverse events, as defined by national toxicity scale.
Time Frame
during the 9 months of observation
Title
Number of Acute Exacerbations
Description
The number of acute exacerbations, defined using consensus criteria (new/worsened hypoxemia and dyspnea, with characteristic radiographic changes within the last 30 days).
Time Frame
during the study duration of 9 months
Title
Absolute Survival Percentage
Description
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).
Time Frame
during 9 months of observation
Title
Transplant-Free Survival
Description
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).
Time Frame
during 9 months of observation
Title
Hospitalizations
Description
The number of hospitalizations in the two arms will be compared.
Time Frame
during 9 months of observation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven R Duncan, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Minnestoa
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19122
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis
We'll reach out to this number within 24 hrs