RCT of Nintedanib in Fibrotic Sarcoidosis

NCT06479603 | Recruiting Phase 4

• 1 other identifier: INT/IEC/2023/SPL-1214
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Sarcoidosis is generally managed with outdoor immune modulatory drugs, most commonly oral steroids and at times drugs like methotrexate or azathioprine as a steroid sparing agent. Around 15-20% of sarcoidosis patient develop fibrosis of the lung parenchyma. The effect of antifibrotics in such patients needs more studies. Nintedanib has been used with good results in patients with fibrosing interstitial lung disease like IPF, SSC- ILD, and other progressive fibrosing ILD. By using nintedanib in fibrotic sarcoidosis it may be possible to limit the functional disability in these patients by slowing the rate of fibrosis and loss of lung function. The use of nintedanib if results in decrease in fibrosis and consequent decline in loss of lung function then it may be a safe and viable option for such patients. The hypothesis of this study is that in patients with fibrotic sarcoidosis on standard of care anti-inflammatory therapy, nintedanib may help in reducing the rate of decline in lung function and progressive fibrosis. The aim is to evaluate the efficacy and safety of nintedanib in subjects with fibrotic sarcoidosis

Conditions

Sarcoidosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• The difference in the mean change in forced vital capacity (FVC) between the study groups

  The FVC will be measured at baseline and 12 months using spirometry performed by an expert technician

  12 months

Secondary Outcomes (5)

• The difference in the mean change in forced expiratory volume in one sec (FEV1) between the study groups

  12 months

• The difference in the mean change in the 6-minute walk distance (6MWD) between the study groups at the end of 12 months

  12 months

• The difference in the mean change in the diffusing capacity of lung for carbon mono oxide (DLCO) between the study groups

  12 months

• Treatment-related adverse effects

  12 months

• Change in the sarcoidosis-related quality-of-life

  12 months

Study Arms (2)

NIntedanib

ACTIVE COMPARATOR

The subjects will receive oral nintedanib. It will be prescribed to be taken after meals with 12 hrs gap between doses. The drug will be started at a dose of 100 mg twice daily. After 2 weeks, the dose will be titrated up to 150 mg twice daily, which will be continued till the end of 52 weeks. The standard-of-care immunosuppressive treatment will be continued along with the study drug (nintedanib). In case of intolerance to the 300 mg/day dose of nintedanib, the dose will be reduced to 100 mg twice daily.

Drug: Nintedanib

Standard of care

ACTIVE COMPARATOR

The subjects will receive the standard-of-care immunosuppressive treatment alone.

Drug: Standard of care

Interventions

Nintedanib DRUG

The subjects will receive oral nintedanib. It will be prescribed to be taken after meals with 12 hrs gap between doses. The drug will be started at a dose of 100 mg twice daily. After 2 weeks, the dose will be titrated up to 150 mg twice daily, which will be continued till the end of 52 weeks. The standard-of-care immunosuppressive treatment will be continued along with the study drug (nintedanib). In case of intolerance to the 300 mg/day dose of nintedanib, the dose will be reduced to 100 mg twice daily. In case of severe adverse effects, the drug will be stopped and reintroduced after a period of up to 1-4 weeks. A dose of 100 mg twice daily will be started and continued. One attempt to titrate the dose up to 150 mg twice daily will be permitted.

NIntedanib

Standard of care DRUG

The subjects will receive the standard-of-care immunosuppressive treatment alone that may include glucocorticoids and other steroid-sparing agents that the subject would already be receiving.

Standard of care

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age more than 18 years
• Presence of signs of fibrosis on a computed tomography scan such as coarse reticulation, irregular lines, traction bronchiectasis, fibrotic masses, or honeycombing involving ≥20% of the lung fields on visual examination
• Having symptoms of breathlessness grade 1 or more on the modified Medical Research Council (mMRC) scale or persistent cough for more than 3 months
• Forced vital capacity (FVC) \<80% predicted value for the age and sex of the subject using the reference equations for our subjects OR an exertional desaturation of 4% or more on a six-minute walk test (6MWT)
• Receiving stable immunomodulatory treatment which includes standard of care drugs such as glucocorticoids alone or in combination with methotrexate, azathioprine, or mycophenolate mofetil for more than 3 months in a stable dose

You may not qualify if:

• Known cardiopulmonary or other comorbid illness that can explain the subject's illness except group 3 pulmonary hypertension due to fibrotic pulmonary sarcoidosis
• Hypersensitivity or contraindication to nintedanib (including high dose antiplatelets or anticoagulants, and bleeding diatheses)
• Received an antifibrotic drug such as pirfenidone or nintedanib for ≥8 weeks in the past one year
• Baseline deranged liver function (alanine aminotransferase and aspartate aminotransferase or bilirubin more than 1·5 times the upper normal limit \[except in the case of Gilbert's syndrome\])
• Serum creatinine higher than 2.0 mg/dL
• Uncontrolled congestive heart failure
• Other serious concomitant medical illness (eg, cancer), chronic debilitating illness (other than chronic HP), or drug abuse
• Pregnancy (documented by urine pregnancy test) or breastfeeding
• Unwilling to participate in the study

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Postgraduate Institute of Medical Education and Research

Chandigarh, India

RECRUITING

MeSH Terms

Conditions

Sarcoidosis, Pulmonary

Interventions

nintedanib; Standard of Care

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Sarcoidosis; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: June 28, 2024
• Study Start: June 30, 2024
• Primary Completion: December 31, 2025
• Study Completion: January 31, 2026
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

IN (1)