Idiopathic Pulmonary Fibrosis
Conditions
Keywords
IPF, Pulmonary Fibrosis, n-acetylcysteine, NAC
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.
Interventions
DRUGN-acetyl cysteine
600 mg N-acetylcysteine (NAC) oral tablets three times daily for 24 months.
DRUGPlacebo
Matching oral placebo tablet three times daily for 24 months.
Sponsors
Fernando J Martinez
University of Virginia
University of Michigan
Pulmonary Fibrosis Foundation
University of Washington
National Heart, Lung, and Blood Institute (NHLBI)
Three Lakes Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The participant and site personnel will not know which study treatment the participant is receiving.
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.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause. | 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 | 24 months | — |
| Time to first respiratory hospitalization, lung transplant, or death from any cause | 24 months | Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee. |
| Time to 10% relative decline in FVC, lung transplant or death from any cause | 24 months | — |
| Time to lung transplant, or death from any cause | 24 months | — |
| Time to 10% relative decline in FVC %predicted, lung transplant, or death from any cause | 24 months | — |
| Time to first all-cause hospitalization, lung transplant, or death from any cause | 24 months | — |
| Annualized rate of respiratory hospitalizations | 24 months | — |
| Annualized rate of non-elective, all-cause hospitalizations | 24 months | — |
| Absolute change in FVC % predicted from randomization at 12 months | 12 months | — |
| Absolute change in FVC % predicted from randomization at 24 months | 24 months | — |
| Absolute change in FVC from randomization at 12 months | 12 months | — |
| Absolute change in FVC from randomization at 24 months | 24 months | — |
| Absolute change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months | 12 months | — |
| Absolute change in DLCO uncorrected from randomization at 24 months | 24 months | — |
| Absolute change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months. | 12 months | — |
| Absolute change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months. | 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. | 12 months | — |
| Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 12 months. | 12 months | — |
| Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months. | 12 months | — |
| Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 24 months | 24 months | — |
| Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months | 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 | 24 months | — |
| Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 24 months | 24 months | — |
| Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months | 24 months | — |
| Proportion of participants with and number of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and unanticipated problems | 24 months | — |
| Estimated time per six months free of 10% relative decline in FVC, first respiratory hospitalization, lung transplant or death from any cause. | 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. | 24 months | — |
| Estimated time lived per six months (based on all-cause mortality). | 24 months | — |
| Average time per six months free of first respiratory hospitalization, lung transplantation or death from any cause. | 24 months | — |
| Average time per six months free of 10% relative decline in FVC, lung transplant, or death from any cause. | 24 months | — |
| Average time per six months free of lung transplant, or death from any cause. | 24 months | — |
| Average time per six months free of 10% relative decline in FVC % predicted, lung transplant, or death from any cause. | 24 months | — |
| Average time per six months free of all-cause hospitalization, lung transplant, or death from any cause. | 24 months | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFernando J Martinez, MD
University of Massachusetts Chan Medical School
PRINCIPAL_INVESTIGATORImre Noth, MD
University of Virginia
PRINCIPAL_INVESTIGATORKevin Flaherty, MS, MD
University of Michigan
PRINCIPAL_INVESTIGATORCathie Spino, ScD
University of Michigan
Outcome results
None listed