Nintedanib for the Treatment of SARS-Cov-2 Induced Pulmonary Fibrosis

NCT04541680 | Recruiting Phase 3 DMC

• 1 other identifier: APHP200527
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, there is no approved treatment for COVID-19 in France, either for the acute phase, nor for the late chronic phase. the investigator suggest that nintedanib has the potential to block the development of lung fibrosis when initiated early enough to inhibit the activation of mesenchymal cells and the progression of virus-induced pulmonary fibrosis. Computerized Tomography (CT) manifestations of fibrosis or fibrous stripes are described in COVID-19 (Ye, Eur Radiol 2020). Pan et al observed fibrous stripes in 17% patients in the early phase of the disease (Pan, Eur Radiol 2020). Ye et al observed bronchiectasis in 2 patients (15.4%) and evidence of pulmonary fibrosis in 3 patients (23.7%) at HRCT performed at 4 weeks (Ye, Eur Radiol 2020). Long term data are still lacking in patients with COVID-19 and the investigators do not know how many patients will have fibrotic sequelae from the acute illness.

Conditions

SARS-Cov-2 Induced Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• The primary objective is to assess whether nintedanib slows the progression of lung fibrosis in COVID-19 survivors as assessed by the decline in the forced vital capacity (FVC) over 12 months compared to placebo.

  Change in Forced Vital Capacity over 12 months assessed by Annual Rate of Decline in FVC in Overall Population

  at inclusion and 12 months.

Secondary Outcomes (10)

• compare the rate of decline of DLCO over 12 months

  at inclusion, 6 and 12 months

• compare exercise capacity at 12 months

  at 12 months

• compare high resolution CT (HRCT) lung opacities extension at 12 months

  at inclusion and 12 months

• compare change in health-related quality of life

  at 12 months

• compare the evolution of dyspnea over time

  at 3, 6, 9 and 12 months

Study Arms (2)

Nintedanib

EXPERIMENTAL

Experimental group will receive nintedanib 150mg BID for 12 months in addition to standard of care (SoC). Nintedanib dose could be reduced to 100mg BID depending on tolerance according to investigator in charge of the patient. The prescription of SoC drugs or procedure will be let to the choice of the investigator in charge of the patient.

Drug: Nintedanib 150 MG [Ofev]

Placebo

PLACEBO COMPARATOR

Control group will receive Placebo BID for 12 months in addition to SoC. The prescription of SoC drugs or procedure will be let to the choice of the investigator in charge of the patient. Standard of care may include pulmonary rehabilitation.

Other: Placebo

Interventions

Nintedanib 150 MG [Ofev] DRUG

Experimental group will receive nintedanib 150mg BID for 12 months in addition to standard of care (SoC). Nintedanib dose could be reduced to 100mg BID depending on tolerance according to investigator in charge of the patient. The prescription of SoC drugs or procedure will be let to the choice of the investigator in charge of the patient.

Nintedanib

Placebo OTHER

Placebo

Also known as: NaCl

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of hospitalization for COVID-19 infection documented with positive PCR or positive serology in the previous 2 to 12 months
• Lung opacities on HRCT involving more than 10% of the lung volume, with fibrotic features
• DLCO≤ 70% of the predicted value

You may not qualify if:

• Pre-existing lung disorder with abnormal HRCT (including COPD, lung cancer, or pulmonary fibrosis)
• Laboratory parameter thresholds:
• renal insufficiency with following criteria: Creatinine clearance \<30 ml/min estimated by the Cockcroft-Gault equation.
• any of the following liver test criteria above the specified limit: Total bilirubin \> 1.5 above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert's syndrome). Aspartate or alanine aminotransferase (AST or ALT) \>3 × ULN (refer to the protocol, Table 3 p 34 for the management of liver enzyme elevation).
• Recent surgery with wound healing in progress(\<7days )
• Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
• 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 catheterisation showing a cardiac index ≤2 L/min/m²
• PAH requiring parenteral therapy with epoprostenol/treprostinil.
• History of cardiovascular diseases, any of the following:
• Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 months of Visit 1
• Myocardial infarction within 6 months of Visit 1
• Unstable cardiac angina within 6 months of Visit 1.
• Bleeding risk, any of the following:

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Pneumologie

Paris, 95018, France

RECRUITING

MeSH Terms

Interventions

nintedanib

Central Study Contacts

Bruno Crestani, MD,PHD

CONTACT

01 40 25 68 00; bruno.crestani@aphp.fr

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: August 17, 2020
• First Posted: September 9, 2020
• Study Start: October 29, 2020
• Primary Completion: October 11, 2023
• Study Completion: July 1, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

FR (1)