Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis

NCT01969409 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HL119960
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 7

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.

Conditions

Ambulatory IPF

Keywords

Lung; Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

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

  baseline to 9 months

• Changes in Forced Vital Capacity (FVC)

  baseline thru 9 months

• Number of Adverse Events (AE)

  during the 9 months of observation

• Number of Acute Exacerbations

  during the study duration of 9 months

• Absolute Survival Percentage

  during 9 months of observation

Study Arms (2)

Placebo

PLACEBO COMPARATOR

These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.

Drug: Placebo

Rituximab

EXPERIMENTAL

Rituximab i.v. given on two occasions, with 14 days between doses.

Drug: Rituximab

Interventions

Rituximab DRUG

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

Rituximab

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.

Also known as: Placebo (D5W) i.v.

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institutes of Health (NIH): collaborator

Study Sites (7)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnestoa

Minneapolis, Minnesota, 55455, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Temple University

Philadelphia, Pennsylvania, 19122, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Fibrosis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Steven R. Duncan, MD
• Organization: University of Alabama at Birmingham

duncsr19@uab.edu

(205) 934-5017

Study Officials

• Steven R Duncan, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Priniciple Investigator

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 25, 2013
• Study Start: January 1, 2014
• Primary Completion: January 31, 2019
• Study Completion: November 30, 2020
• Last Updated: August 21, 2024
• Results First Posted: November 18, 2021

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)