Clinical trial NCT04300920: Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial
Official title: Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: IPF
Pulmonary Fibrosis
n-acetylcysteine
NAC
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: University of Virginia
name: University of Michigan
name: Pulmonary Fibrosis Foundation
name: University of Washington
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Three Lakes Foundation
First posted: 2020-03-09
Enrollment: 202
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 three times daily or matched placebo for 24 months.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 24 months
Secondary outcomes:
measure: Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.
timeFrame: 24 months
measure: Time to death from any cause
timeFrame: 24 months
measure: Time to first respiratory hospitalization, lung transplant, or death from any cause
timeFrame: 24 months
measure: Time to 10% relative decline in FVC, lung transplant or death from any cause
timeFrame: 24 months
measure: Time to lung transplant, or death from any cause
timeFrame: 24 months
measure: Time to 10% relative decline in FVC %predicted, lung transplant, or death from any cause
timeFrame: 24 months
measure: Time to first all-cause hospitalization, lung transplant, or death from any cause
timeFrame: 24 months
measure: Annualized rate of respiratory hospitalizations
timeFrame: 24 months
measure: Annualized rate of non-elective, all-cause hospitalizations
timeFrame: 24 months
measure: Absolute change in FVC % predicted from randomization at 12 months
timeFrame: 12 months
measure: Absolute change in FVC % predicted from randomization at 24 months
timeFrame: 24 months
measure: Absolute change in FVC from randomization at 12 months
timeFrame: 12 months
measure: Absolute change in FVC from randomization at 24 months
timeFrame: 24 months
measure: Absolute change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months
timeFrame: 12 months
measure: Absolute change in DLCO uncorrected from randomization at 24 months
timeFrame: 24 months
measure: Absolute change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months.
timeFrame: 12 months
measure: Absolute change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months.
timeFrame: 12 months
measure: Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 12 months.
timeFrame: 12 months
measure: Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 12 months.
timeFrame: 12 months
measure: Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months.
timeFrame: 12 months
measure: Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 24 months
timeFrame: 24 months
measure: Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months
timeFrame: 24 months
measure: Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 24 months
timeFrame: 24 months
measure: Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 24 months
timeFrame: 24 months
measure: Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months
timeFrame: 24 months
measure: Proportion of participants with and number of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and unanticipated problems
timeFrame: 24 months
measure: Estimated time per six months free of 10% relative decline in FVC, first respiratory hospitalization, lung transplant or death from any cause.
timeFrame: 24 months
measure: Estimated time per six months free of 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.
timeFrame: 24 months
measure: Estimated time lived per six months (based on all-cause mortality).
timeFrame: 24 months
measure: Average time per six months free of first respiratory hospitalization, lung transplantation or death from any cause.
timeFrame: 24 months
measure: Average time per six months free of 10% relative decline in FVC, lung transplant, or death from any cause.
timeFrame: 24 months
measure: Average time per six months free of lung transplant, or death from any cause.
timeFrame: 24 months
measure: Average time per six months free of 10% relative decline in FVC % predicted, lung transplant, or death from any cause.
timeFrame: 24 months
measure: Average time per six months free of all-cause hospitalization, lung transplant, or death from any cause.
timeFrame: 24 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Austell
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Lisa Lancaster
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Massachusetts Chan Medical School
name: Fernando J Martinez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Imre Noth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Kevin Flaherty, MS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Cathie Spino, ScD
role: PRINCIPAL_INVESTIGATOR
References: