Clinical trial NCT05065190: A Study to Test How Well a Medicine Called Nintedanib Helps People in China With Progressive Lung Fibrosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Diseases, Interstitial
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks Expressed in Milliliter (mL)
timeFrame: From baseline up to Week 52.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Changchun
country: China
facility: The Second Hospital of Jilin University
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Chengdu
country: China
facility: West China Hospital
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
city: Hangzhou
country: China
facility: Hangzhou First People's Hospital
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Med College
city: Wuhan
country: China
facility: Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
Study officials:
References: