Efficacy & Safety of Nintedanib in Patients With Progressive Fibrosing Coal Mine Dust-Induced Interstitial Lung Disease

NCT05067517 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: 2012199067
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Assess efficacy (as measured by annual rate of decline in FVC) and safety. The hypothesis is that nintedanib will be safe and effective therapy for patients with progressive fibrosing CMD-ILD over a period of 52 weeks. Test Article - Nintedanib 150 mg administered PO twice daily or matching placebo. A total of 160 patients meeting inclusion/exclusion criteria will be randomized in a 1:1 ratio to either oral nintedanib 150 mg (n=80) or matching placebo (n=80) twice daily. A randomization scheme will be used that balances the group for potential confounders (proportion with PMF or small opacity-only PF-CMD\_ILD and proportion of ever- or never-smokers). The dose of the study drug may be reduced to 100 mg twice daily or interrupted temporarily to manage adverse events (AEs).

Conditions

Progressive Fibrosing Interstitial Lung Disease

Keywords

Coal Mine Dust

Outcome Measures

Primary Outcomes (5)

• Annual rate of decline in FVC in mL (absolute)

  Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  Baseline after first drug intake (planned post visits with Spirometry test)

• Annual rate of decline in FVC in mL (absolute)

  Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  12 weeks after first drug intake (planned post visits with Spirometry test)

• Annual rate of decline in FVC in mL (absolute)

  Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  24 weeks after first drug intake (planned post visits with Spirometry test)

• Annual rate of decline in FVC in mL (absolute)

  Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  36 weeks after first drug intake (planned post visits with Spirometry test)

• Annual rate of decline in FVC in mL (absolute)

  Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  52 weeks after first drug intake (planned post visits with Spirometry test)

Secondary Outcomes (33)

• FVC change from baseline

  52 weeks after first drug intake (planned post visits with Spirometry test)

• FVC Change from baseline, relative decline % predicted

  52 weeks after first drug intake (planned post visits with Spirometry test)

• Absolute FEV1 annual rate of decline in mL

  52 weeks after first drug intake (planned post visits with Spirometry test)

• Relative decline in FEV1 % predicted

  52 weeks after first drug intake (planned post visits with Spirometry test)

• Change from baseline in FEV1 change % predicted

  52 weeks after first drug intake (planned post visits with Spirometry test)

Study Arms (2)

Nintedanib

ACTIVE COMPARATOR

Nintedanib 150 mg administered PO twice daily

Drug: Nintedanib

Placebo

PLACEBO COMPARATOR

Placebo administered PO twice daily

Drug: Placebo

Interventions

Nintedanib DRUG

Randomized in a 1:1 ratio to either oral nintedanib 150 mg (n=80) or matching placebo (n=80) twice daily.

Also known as: OFEV

Nintedanib

Placebo DRUG

Randomized in a 1:1 ratio to either oral nintedanib 150 mg (n=80) or matching placebo (n=80) twice daily.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent consistent with International Conference on Harmonization Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of pre- existing High Resolution Computer Tomography (HRCT), spirometry or other medical records to reviewer).
• Male or female patients aged \>= 18 years at Visit 1.
• Progressive Fibrosing Coal Mine Dust-Induced Interstitial Lung Disease (PF-CMD- ILD) based on a history of at least 5 years' work in surface or underground coal mining and presence of Progressive Massive Fibrosis (PMF) within 24 months of screening visit; or small opacity pneumoconiosis plus decline in percent predicted FVC of \> 5% relative to high quality spirometry performed 12-24 months prior to screening visit, as assessed by the investigator.
• Pneumoconiotic changes documented on screening chest HRCT. Must include large opacities consistent with PMF or small opacities consistent with pneumoconiosis (as described previously).
• Carbon Monoxide Diffusion Capacity (DLCO) corrected for Hemoglobin (Hb) ≥ 30% and \<80% predicted of normal at screening visit.
• FVC \>= 45% predicted at screening visit.

You may not qualify if:

• For those with PMF and past spirometry data, stable lung function based on a fall in percent predicted FVC of \< 5% relative to most recent high quality spirometry obtained at least 12 months but no more than 5 years prior to screening
• Continued employment in a job such as active mining associated with ongoing coal mine dust or respirable crystalline silica dust exposure.
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \> 1.5 x Upper Limit of Normal (ULN) at screening visit.
• Bilirubin \> 1.5 x ULN at screening visit.
• Creatinine clearance \<30 mL/min calculated by Cockcroft-Gault formula at screening visit.
• Patients with underlying chronic liver disease (Child Pugh B or C hepatic impairment). Child Pugh A patients may be enrolled and started at a dose of 100mg BID
• Previous treatment with nintedanib or pirfenidone.
• Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit.
• Use of any of the following medications for the treatment of Interstitial Lung Disease (ILD): azathioprine (AZA), cyclosporine, MMF, tacrolimus, oral corticosteroids (OCS) \>20mg/day and the combination of OCS+AZA+NAC within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of screening visit. The eligible patients with comorbid rheumatoid arthritis (RA) or other connective tissue diseases (CTD) is expected to be on disease- modifying anti-rheumatic drug (DMARD) e.g. methotrexate or TNF inhibitors. All approved RA/CTD medications are allowed at stable doses at baseline and during the study.
• Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2011 Guidelines.
• Significant Pulmonary Arterial Hypertension (PAH) defined by any of the following
• Previous clinical or echocardiographic evidence of significant right heart failure
• History of right heart catheterization showing a cardiac index \<= 2 l/min/m²
• PAH requiring parenteral therapy with epoprostenol/treprostinil
• In the opinion of the Investigator, other clinically significant pulmonary abnormalities.

Sponsors & Collaborators

• West Virginia University: lead

MeSH Terms

Interventions

nintedanib

Study Officials

• Rahul Sangani, MD

  West Virginia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: October 5, 2021
• Study Start: November 1, 2021
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: February 24, 2025

Record last verified: 2025-02