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[Preprint]. 2024 Feb 28:rs.3.rs-3962419.
doi: 10.21203/rs.3.rs-3962419/v1.

Design of the STRIVE-IPF Trial- Study of Therapeutic Plasma Exchange, Rituximab, and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Tejaswini Kulkarni  1 , Gerard J Criner  2 , Daniel J Kass  3 , Ivan O Rosas  4 , Mary Beth Scholand  5 , Daniel F Dilling  6 , Ross Summer  7 , Steven R Duncan  1
Affiliations

Design of the STRIVE-IPF Trial- Study of Therapeutic Plasma Exchange, Rituximab, and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Tejaswini Kulkarni et al. Res Sq. .

Update in

Abstract

Background: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AEIPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

Methods: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits.

Discussion: The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.Trial Registration ClinicalTrials.gov identifier: NCT03286556.

Keywords: Acute exacerbation of Idiopathic Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; autoantibody reduction; clinical trial; protocol.

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Conflict of interest statement

Additional Declarations: Competing interest reported. TK reports personal fees from Boehringer Ingelheim Inc, Puretech Inc, Veracyte, United Therapeutics, outside of submitted work. DJK reports consulting fees from Callidatas, outside of submitted work. DFD reports personal fees from Boehringer Ingelheim Inc, outside of the submitted work. RS reports personal fees from Iliad Biosciences, outside of the submitted work. MBS reports personal fees from Genentech, Boehringer Ingelheim, Veracyte, United Therapeutics, outside of the submitted work. GJK, IOR and SRD do not have competing interests. Competing Interests TK reports personal fees from Boehringer Ingelheim Inc, Puretech Inc, Veracyte, United Therapeutics, outside of submitted work. DJK reports consulting fees from Callidatas, outside of submitted work. DFD reports personal fees from Boehringer Ingelheim Inc, outside of the submitted work. RS reports personal fees from Iliad Biosciences, outside of the submitted work. MBS reports personal fees from Genentech, Boehringer Ingelheim, Veracyte, United Therapeutics, outside of the submitted work. GJK, IOR and SRD do not have competing interests.

References

    1. Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2022;205(9):e18–e47. - PMC - PubMed
    1. Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018;378(19):1811–23. - PubMed
    1. King TE Jr., Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–92. - PubMed
    1. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–82. - PubMed
    1. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr., et al. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176(7):636–43. - PMC - PubMed

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