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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab. |
|
| Rituximab | Experimental | Rituximab i.v. given on two occasions, with 14 days between doses. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Drug | i.v. rituximab given on two occasions 14 days apart. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Changes in Forced Vital Capacity (FVC) |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Steven R Duncan, MD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Brigham and Women's Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab. 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. |
| FG001 | Rituximab | Rituximab i.v. given on two occasions, with 14 days between doses. Rituximab: i.v. rituximab given on two occasions 14 days apart. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab. 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 7 not analyzed: 4 deaths, 2 transplants, 1 dropout | Posted | Mean | Standard Error | titer | baseline to 9 months |
|
Baseline to 9 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Pneumonia |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| flushing | General disorders | Systematic Assessment | flushing |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven R. Duncan, MD | University of Alabama at Birmingham | (205) 934-5017 | duncsr19@uab.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 23, 2019 | Apr 21, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| 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. |
|
|
FVC values over the observation period will be measured by spirometry, month 9 reported. |
| baseline thru 9 months |
| 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 |
| 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 |
| 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 |
| 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 |
| Hospitalizations | The number of hospitalizations in the two arms will be compared. | during 9 months of observation |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| University of Minnestoa | Minneapolis | Minnesota | 55455 | United States |
| Geisinger Medical Center | Danville | Pennsylvania | 17822 | United States |
| Temple University | Philadelphia | Pennsylvania | 19122 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Withdrawal by Subject |
|
| Rituximab |
Rituximab i.v. given on two occasions, with 14 days between doses. Rituximab: i.v. rituximab given on two occasions 14 days apart. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Rituximab |
Rituximab i.v. given on two occasions, with 14 days between doses. Rituximab: i.v. rituximab given on two occasions 14 days apart. |
|
|
| 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. | 7 not analyzed: 4 deaths, 2 transplants, 1 dropout | Posted | Mean | Standard Error | OD units | 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. | 7 not analyzed: 4 deaths, 2 transplants, 1 dropout | Posted | Mean | Standard Error | liters | 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. | Data not complete in 7 due to 4 deaths, 2 transplants, 1 dropout | Posted | Number | serious adverse events | 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). | Data from 7 incomplete: 4 deaths, 2 transplants, 1 dropout | Posted | Number | acute exacerbations | 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). | 1 dropout (censored event) | Posted | Mean | Standard Error | percent of participants | 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). | 1 dropout | Posted | Mean | Standard Error | percentage of participants | during 9 months of observation |
|
|
|
| Secondary | Hospitalizations | The number of hospitalizations in the two arms will be compared. | incomplete data on 1 dropout | Posted | Number | number of admissions | during 9 months of observation |
|
|
|
| 2 |
| 28 |
| 5 |
| 28 |
| 21 |
| 28 |
| EG001 | Rituximab | Rituximab i.v. given on two occasions, with 14 days between doses. Rituximab: i.v. rituximab given on two occasions 14 days apart. | 2 | 30 | 9 | 30 | 24 | 30 |
|
| Infection | Gastrointestinal disorders | Systematic Assessment | Appendicitis Colitis |
|
| Worsening respiratory function | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Increased dyspnea without acute exacerbation |
|
| cerebral vascular accident | Nervous system disorders | Systematic Assessment | stroke |
|
| syncope | Nervous system disorders | Systematic Assessment | syncope |
|
| Acute exacerbation of idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Acute exacerbation |
|
| Myocardial Infarct | Cardiac disorders | Systematic Assessment | myocardial infarct |
|
| Right ventricular failure | Cardiac disorders | Systematic Assessment | Right heart failure |
|
| carotid revascularization | Nervous system disorders | Systematic Assessment | carotid artery stint |
|
| fever | General disorders | Systematic Assessment | fever self reported |
|
| dry mouth | General disorders | Systematic Assessment | dry mouth |
|
| Infection unspecified (mild) | Infections and infestations | Systematic Assessment | infection |
|
| chest tightness | Cardiac disorders | Systematic Assessment | chest tightness, Not Otherwise Specified (NOS) |
|
| arrhythmia | Cardiac disorders | Systematic Assessment | mild, NOS |
|
| Hypertension | Cardiac disorders | Systematic Assessment | blood pressure elevated greater than usual |
|
| palpitations | Cardiac disorders | Systematic Assessment | self reported palpitations NOS |
|
| Pruritis | Skin and subcutaneous tissue disorders | Systematic Assessment | pruritis |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment | skin rash NOS |
|
| Brusing | Surgical and medical procedures | Systematic Assessment | Ecchymosis |
|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment | abdominal pain self limited and NOS |
|
| Anorexia | Gastrointestinal disorders | Systematic Assessment | loss of appetite |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | diarrhea |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment | nausea with or without vomiting |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment | elevated blood sugar greater than baseline |
|
| Anxiety | Nervous system disorders | Systematic Assessment | anxiety |
|
| Dizzyness | Nervous system disorders | Systematic Assessment | dizziness self reported |
|
| Fatigue | Nervous system disorders | Systematic Assessment | self reported fatigue NOS |
|
| Headache | Nervous system disorders | Systematic Assessment | headache |
|
| Insomnia | Nervous system disorders | Systematic Assessment | trouble sleeping |
|
| cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Cough greater than baseline |
|
| Post-nasal drip | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | post-nasal discharge |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Shortness of breath greater than baseline not attributable to acute exacerbations, pneumonia, or causes other than idiopathic pulmonary fibrosis |
|
| dry eyes | Eye disorders | Systematic Assessment | dry eyes, self-limited |
|
| Backache | Musculoskeletal and connective tissue disorders | Systematic Assessment | back pain, self limited |
|
| Muscle pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Muscle pain other than backache (self limited) |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | Systematic Assessment | self limited joint stiffness |
|
| urinary tract infection | Renal and urinary disorders | Systematic Assessment | urinary tract infection documented by culture or suspected |
|
| Tooth infection | Infections and infestations | Systematic Assessment | tooth infection self-reported |
|
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| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |