A Study to Test How Well a Medicine Called Nintedanib Helps People in China With Progressive Lung Fibrosis

A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib Over 52 Weeks in Chinese Patients With Chronic Fibrosing ILDs With a Progressive Phenotype

This study in China is open to people with progressive lung fibrosis (chronic fibrosing ILDs with progressive phenotype) who are at least 18 years old. The purpose of this study is to find out whether a medicine called nintedanib helps people with progressive lung fibrosis.

Participants are put into 2 groups randomly, which means by chance. 1 group gets nintedanib as capsules twice a day. The other group gets placebo as capsules twice a day. Placebo capsules look like nintedanib capsules but do not contain any medicine.

Participants are in the study for about 1 year. During this time, they visit the study site about 10 times. At some visits, participants perform a lung function test. The doctors check whether study treatment can slow down the loss of lung function. The doctors also regularly check participants' health and take note of any unwanted effects.

Study Overview

• Status: Completed
• Conditions: Lung Diseases, Interstitial
• Intervention / Treatment: Drug: Placebo; Drug: Nintedanib

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100029
    • China-Japan Friendship Hospital
  • Changchun, China, 130041
    • The Second Hospital of Jilin University
  • Changsha, China, 410008
    • Xiangya Hospital, Central South University
  • Chengdu, China, 610042
    • West China Hospital
  • Guangzhou, China, 510120
    • First Affiliated Hospital of Guangzhou Medical University
  • Hangzhou, China, 310013
    • Zhejiang Hospital
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital Zhejiang University School of Medicine
  • Hangzhou, China, 310006
    • Hangzhou First People's Hospital
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital
  • Shanghai, China, 200030
    • Shanghai Chest Hospital
  • Shanghai, China, 200040
    • Huashan Hospital, Fudan University
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Tianjin, China, 30052
    • Tianjin Medical University General Hospital
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Med College
  • Wuhan, China, 430030
    • Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
  • Yinchuan, China, 750004
    • General Hospital of Ningxia Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written Informed Consent consistent with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of High-Resolution Computed Tomography (HRCT) to reviewer.
• Male or female patients aged ≥ 18 years at Visit 1.

• Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Phenotype within 24 months of screening visit (Visit 1) despite treatment with unapproved medications used in clinical practice to treat ILD, as assessed by the investigator:

  • Clinically significant decline in Forced Vital Capacity (FVC) % predicted based on a relative decline of ≥10%
  • Marginal decline in FVC % predicted based on a relative decline of ≥5-<10% combined with worsening of respiratory symptoms
  • Marginal decline in FVC % predicted based on a relative decline of ≥5-<10% combined with increasing extent of fibrotic changes on chest imaging
  • Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging [Note: Changes attributable to comorbidities e.g. infection, heart failure must be excluded. Unapproved medications used in the clinical practice to treat ILD include but are not limited to corticosteroid, azathioprine, mycophenolate mofetil (MMF), n-Acetylcysteine (NAC), rituximab, cyclophosphamide, cyclosporine, tacrolimus].
• Fibrosing lung disease on HRCT, defined as reticular abnormality with traction bronchiectasis with or without honeycombing, with disease extent of >10%, performed within 12 months of Visit 1 as confirmed by central readers.
• For patients with underlying Connective Tissue Disease (CTD): stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit 1.
• FVC ≥ 45% predicted at Visit 2.

Exclusion Criteria:

• Aspartate Aminotransferase (AST) and / or Alanine Aminotransferase (ALT) > 1.5 x Upper Level of Normal (ULN) at Visit 1
• Bilirubin > 1.5 x ULN at Visit 1
• Creatinine clearance <30 milliliter (mL)/minute (min) calculated by Cockcroft-Gault formula at Visit 1.

[Note: Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after randomization. In case at Visit 2 the results do no longer satisfy the entry criteria, the Investigator has to decide whether it is justified that the patient remains on study drug. The justification for decision needs to be documented. Laboratory parameters that are found to be abnormal at Visit 1 are allowed to be re-tested (once) if it is thought to be a measurement error (i.e. there was no abnormal result of this test in the recent history of the patient and there is no related clinical sign) or the result of a temporary and reversible medical condition, once that condition is resolved].

• Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
• Previous treatment with nintedanib or pirfenidone.
• Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit (Visit 1).
• Use of any of the following medications for the treatment of Interstitial Lung Disease (ILD): azathioprine (AZA), cyclosporine, Mycophenolate Mofetil (MMF), tacrolimus, oral corticosteroids (OCS) >20mg/day and the combination of OCS+AZA+ n-Acetylcysteine (NAC) within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of Visit 2.

Note: Patients whose Regulatory Authority (RA)/Connective Tissue Disease (CTD) is managed by these medications should not be considered for participation in the current study unless change in RA/CTD medication is medically indicated.

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 150 mg Nintedanib; A soft gelatin capsule of 150 mg Nintedanib was administered orally twice daily (bid) in Chinese patients with chronic fibrosing ILD with progressive phenotype with over 52 weeks. Dose could be reduced to 100 mg bid to manage adverse events.	Drug: Nintedanib; Soft gelatin capsule
Placebo Comparator: Placebo; A soft gelatin capsule of placebo matching in size, weight, colour and shape to 150 milligram (mg) or 100 mg soft gelatin capsule of Nintedanib, was administered orally twice daily (bid) in Chinese patients with chronic fibrosing Interstitial Lung Disease (ILD) with progressive phenotype with over 52 weeks.	Drug: Placebo; Soft gelatin capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks Expressed in Milliliter (mL)	Annual rate of decline in FVC over 52 weeks expressed in milliliter (mL). The main analysis used a restricted maximum likelihood (REML)-based approach with a random slope and intercept model. The analysis included the fixed, categorical effects of treatment, high resolution computed tomography (HRCT) pattern at baseline, fixed continuous effects of time and baseline FVC as well as the treatment-by-time and baseline-by-time interactions. Random effects were included for the patient response for both time and intercept. For patients who prematurely discontinued study treatment, data collected at follow-up visit and visits after treatment discontinuation was included in the analysis.	From baseline up to Week 52.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2021
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): May 7, 2024

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199-0434

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No