Trial record 5 of 10 for:    idiopathic pulmonary fibrosis | Open Studies | NIH, U.S. Fed

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steven Duncan, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01969409
First received: October 17, 2013
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Ambulatory IPF
Drug: Rituximab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Autoantibodies to HEp-2 Cells [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Titers of anti-HEp-2 autoantibodies, by indirect immunofluorescence assays (IFA) over 9 months


Secondary Outcome Measures:
  • Anti-Heat Shock Protein 70 (HSP70) autoantibodies [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Changes of anti-HSP70 plasma concentrations as determined by ELISA

  • Forced Vital Capacity (FVC) as a percentage of predicted values (FVC%p) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Serial FVC%p values over the observation period will be measured by spirometry.

  • Adverse Event (AE) Rates [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    AE in the two treatment arms will be compared.

  • Acute exacerbation frequency [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The number and frequency of acute exacerbations, defined using consensus criteria (new/worsened hypoxemia and dyspnea, with characteristic radiographic changes within the last 30 days).

  • Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Absolute and transplant-free survival in the two arms.

  • Hospitalization rates [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The frequency and duration of hospitalizations in the two arms will be compared.


Estimated Enrollment: 58
Study Start Date: January 2014
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Ambulatory patients with a diagnosis of IPF, not established >5 years from the enrollment date, that fulfills ATS/ETS Consensus Criteria.

Ability and willingness to give informed consent. Presence of autoantibodies against 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., ANA, RF, Anti-Ro, Anti-LA, Anti-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 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., cyclophosphomide, 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01969409

Contacts
Contact: Steven R Duncan, MD 412-692-2210 duncsr@upmc.edu

Locations
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States
United States, Pennsylvania
Geisinger Medical Center Not yet recruiting
Danville, Pennsylvania, United States
Temple University Not yet recruiting
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: Steven R Duncan, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Steven R Duncan, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Steven Duncan, MD, Priniciple Investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01969409     History of Changes
Other Study ID Numbers: HL119960
Study First Received: October 17, 2013
Last Updated: January 22, 2014
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by University of Pittsburgh:
Lung
Fibrosis

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Lung Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Pathologic Processes
Respiratory Tract Diseases
Autoantibodies
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 18, 2014