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

Idiopathic Pulmonary Fibrosis Clinical Trial

— PRECISIONS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04300920
• Other study ID #: 19-12021232
• Secondary ID: 1U24HL145265-01A
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 17, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 202
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• N-acetyl cysteine
600 mg N-acetylcysteine (NAC) oral tablets three times daily for 24 months.
• Placebo
Matching oral placebo tablet three times daily for 24 months.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Piedmont Healthcare	Austell	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Southern California	Los Angeles	California
United States	Loyola University	Maywood	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	Lisa Lancaster	Nashville	Tennessee
United States	Tulane University	New Orleans	Louisiana
United States	Weill Cornell Medicine	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of Utah Health	Salt Lake City	Utah
United States	University of Texas Health San Antonio	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	Stanford University	Stanford	California
United States	University of Arizona	Tucson	Arizona

Sponsors (7)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Heart, Lung, and Blood Institute (NHLBI), Pulmonary Fibrosis Foundation, Three Lakes Foundation, University of Michigan, University of Virginia, University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 months
Secondary	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.	24 months
Secondary	Time to death from any cause		24 months
Secondary	Time to first respiratory hospitalization	Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.	24 months
Secondary	Time to 10% relative decline in FVC		24 months
Secondary	Time to lung transplant		24 months
Secondary	Time to 10% relative decline in FVC %predicted		24 months
Secondary	Time to first all-cause hospitalization		24 months
Secondary	Annualized rate of respiratory hospitalizations		24 months
Secondary	Annualized rate of non-elective, all-cause hospitalizations		24 months
Secondary	Proportion of participants undergoing lung transplant during follow-up		24 months
Secondary	Change in FVC from randomization at 12 months		12 months
Secondary	Change in FVC % predicted from randomization at 12 months		12 months
Secondary	Change in FVC from randomization at 24 months		24 months
Secondary	Change in FVC % predicted from randomization at 24 months		24 months
Secondary	Change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months		12 months
Secondary	Change in DLCO from randomization at 24 months		24 months
Secondary	Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months.		12 months
Secondary	Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months.		12 months
Secondary	Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 12 months.		12 months
Secondary	Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 12 months.		12 months
Secondary	Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months.		12 months
Secondary	Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 24 months		24 months
Secondary	Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months		24 months
Secondary	Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 24 months		24 months
Secondary	Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 24 months		24 months
Secondary	Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months		24 months
Secondary	Proportion of participants with and number of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and unanticipated problems		24 months