Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

NCT01266317 | Completed Phase 1 Results DMC

• 1 other identifier: PRO10110151
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label Phase I/II trial to assess the feasibility and safety of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration on the outcome of hospitalized patients with acute IPF exacerbations. The specific aims of this study are:

1. 1.To assess the feasibility and safety of combined PEX, rituximab, and conventional corticosteroid administrations for the treatment of hospitalized patients with acute IPF exacerbations by monitoring indices of respiratory (PaO2) and cardiovascular function during the treatment interval.
2. 2.To assess the efficacy of combined PEX, rituximab, and conventional corticosteroid administrations for the treatment of hospitalized patients with acute IPF exacerbations on patient survival in comparison to historical controls. Patient survival for this investigation will be defined using the composite outcome of 60 day survival and/or survival to lung transplantation.

Conditions

IPF

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Respiratory and/or Hemodynamic Deteriorations

  To assess the feasibility and safety of combined PEX, rituximab, and conventional corticosteroid administrations for the treatment of hospitalized patients with acute IPF exacerbations by monitoring indices of respiratory (PaO2) and cardiovascular function during the treatment interval. Respiratory deterioration was defined by a compilations of respiratory deteriorations (deteriorating gas exchange) and hemodynamic deteriorations (defined as a need for medical intervention).

  28 days

Secondary Outcomes (1)

• Number of Participants Survived to 60 Days or to Transplantation

  60 days

Study Arms (1)

Combined PEX, Rituximab and Steroids

EXPERIMENTAL

Standard Steroid Treatment: One gm of methylprednisolone I.V., on day 0, followed by 40 mg/day I.V. on days 1-4, and days 6-12 (or the P.O. prednisone equivalent). Methylprednisolone 100 mg I.V. will be administered on days 5 and 13. Steroid doses will then be 20 mg methylprednisolone I.V. (or P.O. prednisone equivalent) from days 14-28, and then reduced thereafter at the discretion of the principle investigator. Plasma exchange (PEX) will consist of 1.5x estimated plasma volume exchanges for 3 successive days (0, 1,2) and then, after a one day interval to enable equilibration of autoantibodies sequestered in tissues, two more daily treatments on days 4 and 5. Rituximab: One gm I.V. will be administered on day 5 (after completion of the last PEX) and day 13.

Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids

Interventions

Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids DRUG

Standard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab

Combined PEX, Rituximab and Steroids

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society Consensus Criteria.
• Unexplained worsening or development of dyspnea or hypoxemia within 30 days leading to the current hospitalization.
• Radiographic imaging showing ground-glass abnormality and/or consolidation superimposed on a background of reticular or honeycomb pattern consistent with usual interstitial pneumonia.
• Intent on the part of the treating physician to use high dose steroid therapy as a therapeutic effort to treat a diagnosis of acute IPF exacerbation.

You may not qualify if:

• Diagnosis of documented infection based upon clinical evaluation and microbial testing.
• Diagnosis of thromboembolic disease by clinical assessment.
• Diagnosis of an additional etiology for Acute Lung Injury/Acute Respiratory Distress Syndrome based upon clinical assessment to include sepsis, aspiration, trauma, inhalational injury, acute pancreatitis, drug toxicity, blood product transfusion reaction, or stem cell transplantation.
• Diagnosis of congestive heart failure that accounts for the hypoxemia.
• Presence of active hepatitis B infection.
• Coagulopathy defined as an International Normalized Ratio \> 1.8, Partial Thromboplastin Time \> 2 x control, and platelet count \< 50,000.
• Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus or uncontrolled hypertension (systolic BP \> 160 mm Hg and diastolic BP \> 100 mm Hg) which would contraindicated the use of corticosteroids.
• Hemodynamic instability defined as a vasopressor requirement which would contraindicate the use of plasmapheresis.
• History of reaction to blood products, murine-derived products, or prior exposures to human-murine chimeric antibodies,
• History of malignancy.
• Inability or unwillingness to accept a blood transfusion.
• Inability or unwillingness to complete post- treatment surveillance for 60 days.
• Diagnosis of major comorbidities expected to interfere with subjects study participation for 60 days.

Sponsors & Collaborators

• Michael Donahoe: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Interventions

PHEX Phosphate Regulating Neutral Endopeptidase; Rituximab; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

This was a pilot, open-label trial of an unprecedented regimen for a highly lethal disease and, as such, included only small numbers of subjects and historical controls.

Results Point of Contact

• Title: Dr. Michael Donahoe
• Organization: University of Pittsburgh

donahoem@upmc.edu

412-383-2049

Study Officials

• Michael Donahoe, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 22, 2010
• First Posted: December 24, 2010
• Study Start: March 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: March 14, 2018
• Results First Posted: January 24, 2018

Record last verified: 2018-02

Locations

US (1)