Autoantibody Reduction Therapy for Progressive Idiopathic Pulmonary Fibrosis

NCT07674745 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB-300016700PR251064
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 9

Brief Summary

This Phase IIb trial will compare effectiveness and safety of a multi-component autoantibody reduction therapy (AART), consisting of therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIg) for treatment of patients with progressive idiopathic pulmonary fibrosis (IPF).

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Progression; Autoantibodies

Outcome Measures

Primary Outcomes (1)

• Forced Vital Capacity (FVC)

  Intergroup comparisons of FVC changes over duration of observations

  180 days or latest available observation (e.g., at 30, 90, or 180 days after randomization)

Secondary Outcomes (4)

• Supplemental Oxygen Requirements (O2)

  180 days or latest available observation (e.g., at 30, 90, or 180 days after randomization)

• Six-minute walk distances (6MWD)

  180 days or latest available observation (e.g., at 30, 90, or 180 days after randomization)

• Durations of progression-free survival

  180 days or latest available observation (e.g., at 30, 90, or 180 days after randomization)

• Composite outcome measure

  180 days or latest available observation (e.g., at 30, 90, or 180 days after randomization)

Study Arms (2)

Autoantibody Reduction Therapy (AART)

EXPERIMENTAL

Patients will be treated with combination of five (5) therapeutic plasma exchanges, followed by one dose of rituximab and then followed with four infusions of intravenous immunoglobulin (IVIg)

Other: Therapeutic Plasma Exchange; Drug: Rituximab; Drug: Intravenous immunoglobulin

Treatment as Usual (TAU)

ACTIVE COMPARATOR

Patients will continue treatment(s) with optimized approved medications for idiopathic pulmonary fibrosis (IPF)

Drug: Treatment as Usual

Interventions

Therapeutic Plasma Exchange OTHER

Removal of patient's plasma by mechanical means and replacement with saline and albumin or normal plasma

Also known as: Plasmapheresis

Autoantibody Reduction Therapy (AART)

Rituximab DRUG

Infusion of humanized mouse monoclonal antibody with specificity for human CD20

Also known as: ritux

Autoantibody Reduction Therapy (AART)

Intravenous immunoglobulin DRUG

intravenous infusions of normal human immunoglobulin

Also known as: IVIg

Autoantibody Reduction Therapy (AART)

Treatment as Usual DRUG

Continued therapy with conventional, approved, specific IPF medications

Treatment as Usual (TAU)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 40-85 years old.
• A diagnosis of IPF that fulfills latest ATS/ERS Consensus Criteria.
• A diagnosis of Progressive IPF (P-IPF), defined as a relative decrease of FVC%p \>10% during the preceding twelve months, and substantiated by replicate values at least three weeks apart.
• Ability and willingness to give informed consent (no surrogates) and adhere to requirements.
• Have eligibility confirmed by a consensus of trial investigators.
• Is not now or has been in experimental regimen for at least 2 weeks (or 5 half-lives of agent) and agrees to not become participants in other experimental regimens (other than solely observational registries) for the duration of their participation in this trial (180 days).
• Has been immunized with 2025-2026 COVID-19 vaccine (and later versions as they become available) between 1 and 26 weeks prior to randomization.
• IPF duration \<10 years, based on the date of definitive diagnosis.
• Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) \>0.70

You may not qualify if:

• Diagnoses of current infection by clinical or microbial assessments.
• Diagnoses of an additional or alternative etiology for lung dysfunction based upon clinical assessment, including sepsis, congestive heart failure, thromboembolism, worsened pulmonary artery hypertension, etc. using routine clinical evaluations under direction of the attending physician.
• History or serologic evidence of hepatitis B or C infection. Positive serology for Hepatitis C will not exclude patients if their circulating HC virus RNA test is negative.
• Coagulopathy, defined as an INR \>1.6, PTT \>2x control, fibrinogen \<100 mg/dL, or platelet count \<50,000 unless these abnormalities can be reversed.
• Uncontrolled diabetes or hypertension (systolic BP \>160 mm Hg and diastolic BP \>100 mm Hg) that would contraindicate use of corticosteroids.
• Hemodynamic instability, defined as an inotrope or vasopressor requirement.
• History of reactions to blood products, murine-derived products, or prior rituximab use within the last six months.
• History of malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, the latter defined as stage T1 or T2a, with prostate specific antigen \<10 ng/dl. AART is not known to promote cancer, and these criteria are within current guidelines.
• Unwillingness to accept blood product transfusion.
• Diagnosis of major comorbidities expected to interfere with study participation.
• Treatment for \>14 days within the preceding month with \>20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immuno-suppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, etc.), or with rituximab (or other anti-B-cell biological agents) within the last 6 months.
• Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted (to obviate hemodynamic lability during TPE).
• Fertile women who do not agree to contraception or abstinence. IPF is a disease of older adults, and male predominant, so this will not be a frequent consideration.
• An alternative, concordant or historical diagnosis of interstitial lung diseases other than IPF, including idiopathic fibrosis with autoimmune features (IPAF) per clinical domain.1
• IgA deficiency, to preclude IVIg reactions.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35216, United States

Location

Loyola University

Chicago, Illinois, 60153, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas

Kansas City, Kansas, 60611, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 60611, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• Donahoe M, Valentine VG, Chien N, Gibson KF, Raval JS, Saul M, Xue J, Zhang Y, Duncan SR. Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis. PLoS One. 2015 Jun 17;10(6):e0127771. doi: 10.1371/journal.pone.0127771. eCollection 2015.

  PMID: 26083430 RESULT

• Kulkarni T, Criner GJ, Kass DJ, Rosas IO, Scholand MB, Dilling DF, Summer R, Duncan SR. Design of the STRIVE-IPF trial- study of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin for acute exacerbations of idiopathic pulmonary fibrosis. BMC Pulm Med. 2024 Mar 20;24(1):143. doi: 10.1186/s12890-024-02957-3.

  PMID: 38509495 RESULT

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Disease Progression

Interventions

Plasma Exchange; Plasmapheresis; Rituximab; Immunoglobulins, Intravenous; Therapeutics

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin G; Immunoglobulin Isotypes

Study Officials

• Steven R Duncan, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven R Duncan, MD

CONTACT

4122156977; srduncan@uabmc.edu

Teja Kulakarni, MD

CONTACT

205-975-6770; tkulkarni@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized to experimental treatment (autoantibody reduction therapy- AART) or Treatment as Usual- 2 arms

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: June 30, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): March 31, 2031
• Last Updated: July 1, 2026

Record last verified: 2026-06

Locations

US (9)