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

• ClinicalTrials.gov Identifier: NCT04300920
• Recruitment Status: Recruiting
• First Posted: March 9, 2020
• Last Update Posted: March 22, 2023
• Sponsor: Weill Medical College of Cornell University
• Collaborators: University of Virginia; University of Michigan; Pulmonary Fibrosis Foundation; University of Washington; National Heart, Lung, and Blood Institute (NHLBI); Three Lakes Foundation
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Tracking Information

• First Submitted Date: March 6, 2020
• First Posted Date: March 9, 2020
• Last Update Posted Date: March 22, 2023
• Actual Study Start Date: December 17, 2020
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 6, 2020)

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. [ Time Frame: 24 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 9, 2020)

• Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause. [ Time Frame: 24 months ]
  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 to death from any cause [ Time Frame: 24 months ]
• Time to first respiratory hospitalization [ Time Frame: 24 months ]
  Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
• Time to 10% relative decline in FVC [ Time Frame: 24 months ]
• Time to lung transplant [ Time Frame: 24 months ]
• Time to 10% relative decline in FVC %predicted [ Time Frame: 24 months ]
• Time to first all-cause hospitalization [ 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 ]
• Proportion of participants undergoing lung transplant during follow-up [ Time Frame: 24 months ]
• Change in FVC from randomization at 12 months [ Time Frame: 12 months ]
• Change in FVC % predicted from randomization at 12 months [ Time Frame: 12 months ]
• Change in FVC from randomization at 24 months [ Time Frame: 24 months ]
• Change in FVC % predicted from randomization at 24 months [ Time Frame: 24 months ]
• Change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months [ Time Frame: 12 months ]
• Change in DLCO from randomization at 24 months [ Time Frame: 24 months ]
• Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months. [ Time Frame: 12 months ]
• 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 ]

Original Secondary Outcome Measures (submitted: March 6, 2020)

• Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause. [ Time Frame: 24 months ]
  This is a composite endpoint of time to 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause. Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
• Time to death from any cause [ Time Frame: 24 months ]
• Time to first respiratory hospitalization [ Time Frame: 24 months ]
  Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
• Time to 10% relative decline in FVC [ Time Frame: 24 months ]
• Time to lung transplant [ Time Frame: 24 months ]
• Time to 10% relative decline in FVC %predicted [ Time Frame: 24 months ]
• Time to first all-cause hospitalization [ 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 ]
• Proportion of participants undergoing lung transplant during follow-up [ Time Frame: 24 months ]
• Change in FVC from randomization at 12 months [ Time Frame: 12 months ]
• Change in FVC % predicted from randomization at 12 months [ Time Frame: 12 months ]
• Change in FVC from randomization at 24 months [ Time Frame: 24 months ]
• Change in FVC % predicted from randomization at 24 months [ Time Frame: 24 months ]
• Change in diffusing capacity of the lung for carbon monoxide (DLCO) corrected for hemoglobin from randomization at 12 months [ Time Frame: 12 months ]
• Change in DLCO from randomization at 24 months [ Time Frame: 24 months ]
• Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months. [ Time Frame: 12 months ]
• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The participant and site personnel will not know which study treatment the participant is receiving.

Primary Purpose: Treatment

• Condition: Idiopathic Pulmonary Fibrosis

Intervention

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

Study Arms

• Experimental: N-acetylcysteine
  600 mg oral N-acetylcysteine (NAC) three times daily for 24 months.
  Intervention: Drug: N-acetyl cysteine
• Placebo Comparator: Placebo
  Placebo tablet three times daily for 24 months.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 6, 2020): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Betsy Peters; 646-962-2742; elp2018@med.cornell.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04300920
• Other Study ID Numbers: 19-12021232; 1U24HL145265-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The de-identified analytic data will be prepared as SAS transport files or ASCII comma-delimited files with accompanying codebooks that describe the data and data structure. The redaction will employ best practices and will be consistent with NHLBI data sharing policies.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: 3 years after the end of the study or 2 years after the main paper reporting the results of the trial, whichever comes first.
• Access Criteria: Data will be shared through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).
• URL: https://biolincc.nhlbi.nih.gov/home/

• Current Responsible Party: Weill Medical College of Cornell University
• Original Responsible Party: Same as current
• Current Study Sponsor: Weill Medical College of Cornell University
• Original Study Sponsor: Same as current

Collaborators

• University of Virginia
• University of Michigan
• Pulmonary Fibrosis Foundation
• University of Washington
• National Heart, Lung, and Blood Institute (NHLBI)
• Three Lakes Foundation

Investigators

• Principal Investigator: Fernando J Martinez, MD; Weill Medical College of Cornell University
• Principal Investigator: Imre Noth, MD; University of Virginia
• Principal Investigator: Kevin Flaherty, MS, MD; University of Michigan
• Principal Investigator: Cathie Spino, ScD; University of Michigan

• PRS Account: Weill Medical College of Cornell University
• Verification Date: March 2023