Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial

Fernando J Martinez202 enrolled

Overview

The purpose of this study is to compare the effect of n-acetylcysteine (NAC) plus standard care with matched placebo plus standard of care in patients diagnosed with idiopathic pulmonary fibrosis (IPF) who have the TOLLIP rs3750920 TT genotype. The study will compare the time to a composite endpoint of relative decline in lung function \[10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or all-cause mortality\] The secondary objectives will be to examine the effect of NAC on the components of the primary composite endpoint, the rates of clinical events, change in physiology, change in health status, and change in respiratory symptoms.

This is a multi-center, randomized, double-blind, placebo-controlled trial of NAC or placebo in about 200 participants with IPF with a TOLLIP rs3750920 TT genotype. Eligible participants will be randomized in a 1:1 fashion to NAC or placebo, stratified by stable concomitant IPF therapy use (i.e., pirfenidone or nintedanib administered for at least 6 weeks prior to screening) versus no pirfenidone or nintedanib use. Participants will receive 600 mg NAC orally or matched placebo to take three times daily for 24 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

202

Conditions

Idiopathic Pulmonary Fibrosis

N-acetyl cysteineDRUG

600 mg N-acetylcysteine (NAC) oral tablets three times daily for 24 months.

PlaceboDRUG

Matching oral placebo tablet three times daily for 24 months.

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * ≥ 40 years of age * Diagnosed with IPF according to 2018 ATS/ERS/JRS/ALAT, confirmed by enrolling investigator * Signed informed consent * If taking pirfenidone or nintedanib, must be on stable dose for at least 6 weeks prior to enrollment visit * Confirmed rs3570920 TT TOLLIP genotype Exclusion Criteria: * Pregnancy or planning to become pregnant * Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of \<1% per year during study participation * Significant medical, surgical or psychiatric illness that in the opinion of the investigator would affect subject safety, including liver and renal failure * Receipt of an investigational drug or biological agent within the previous 4 weeks of the screening visit or 5 times the half-life, if longer * Supplemental or prescribed NAC therapy within 60 days of enrollment * Listed for lung transplantation at the time of screening * History of lung cancer * Inability to perform spirometry * Forced vital capacity (FVC) less than 45% predicted, using the global lung function index (GLI) equation at Visit 1 * Active respiratory infection requiring treatment with antibiotics within 4 weeks of Visit 1

Locations (25)

University of Arizona

Tucson, Arizona, United States

University of Southern California

Los Angeles, California, United States

Stanford University

Stanford, California, United States

University of Colorado

Aurora, Colorado, United States

Piedmont Healthcare

Austell, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Loyola University

Maywood, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Tulane University

New Orleans, Louisiana, United States

...and 15 more locations

Outcomes

Primary Outcomes

Time to one of the following composite endpoint criteria: 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplant or death from any cause.

This is a composite endpoint of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplant or death from any cause. Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.

Time frame: 24 months

Secondary Outcomes

Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.

This is a composite endpoint of time to 10% relative decline in FVC % predicted, based on the global lung initiative (GLI) reference equation, first respiratory hospitalization, lung transplant or death from any cause. Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.

Time frame: 24 months

Time to death from any cause

Time frame: 24 months

Time to first respiratory hospitalization, lung transplant, or death from any cause

Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.

Time frame: 24 months

Time to 10% relative decline in FVC, lung transplant or death from any cause

Time frame: 24 months

Time to lung transplant, or death from any cause

Time frame: 24 months

Time to 10% relative decline in FVC %predicted, lung transplant, or death from any cause

Time frame: 24 months

Time to first all-cause hospitalization, lung transplant, or death from any cause

Time frame: 24 months

Annualized rate of respiratory hospitalizations

Time frame: 24 months

Annualized rate of non-elective, all-cause hospitalizations

Time frame: 24 months

Absolute change in FVC % predicted from randomization at 12 months

Time frame: 12 months

Absolute change in FVC % predicted from randomization at 24 months

Time frame: 24 months

Absolute change in FVC from randomization at 12 months

Time frame: 12 months

Absolute change in FVC from randomization at 24 months

Time frame: 24 months

Absolute change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months

Time frame: 12 months

Absolute change in DLCO uncorrected from randomization at 24 months

Time frame: 24 months

Absolute change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months.

Time frame: 12 months

Absolute change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months.

Time frame: 12 months

Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 12 months.

Time frame: 12 months

Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 12 months.

Time frame: 12 months

Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months.

Time frame: 12 months

Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 24 months

Time frame: 24 months

Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months

Time frame: 24 months

Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 24 months

Time frame: 24 months

Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 24 months

Time frame: 24 months

Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months

Time frame: 24 months

Proportion of participants with and number of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and unanticipated problems

Time frame: 24 months

Estimated time per six months free of 10% relative decline in FVC, first respiratory hospitalization, lung transplant or death from any cause.

Time frame: 24 months

Estimated time per six months free of 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.

Time frame: 24 months

Estimated time lived per six months (based on all-cause mortality).

Time frame: 24 months

Average time per six months free of first respiratory hospitalization, lung transplantation or death from any cause.

Time frame: 24 months

Average time per six months free of 10% relative decline in FVC, lung transplant, or death from any cause.

Time frame: 24 months

Average time per six months free of lung transplant, or death from any cause.

Time frame: 24 months

Average time per six months free of 10% relative decline in FVC % predicted, lung transplant, or death from any cause.

Time frame: 24 months

Average time per six months free of all-cause hospitalization, lung transplant, or death from any cause.

Time frame: 24 months

Data from ClinicalTrials.gov

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Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial

Overview

Conditions

Interventions

Eligibility

Locations (25)

Outcomes

Primary Outcomes

Secondary Outcomes