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

Fernando J Martinez

Status and phase: Active, not recruiting; Phase 3

Conditions: Idiopathic Pulmonary Fibrosis

Treatments: Drug: Placebo; Drug: N-acetyl cysteine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04300920

1U24HL145265-01A1 (U.S. NIH Grant/Contract)

19-12021232

Details and patient eligibility

About

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.

Full 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.

Enrollment: 202 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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202 participants in 2 patient groups, including a placebo group

N-acetylcysteine

Experimental group

Description:

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

Treatment:

Drug: N-acetyl cysteine

Placebo

Placebo Comparator group

Description:

Placebo tablet three times daily for 24 months.

Treatment:

Drug: Placebo