Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects

NCT03562416 | Terminated Phase 2 FDA Drug

• 1 other identifier: 1199-0329
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess the utility of nintedanib therapy in addition to usual transplant care in single lung transplant recipients with idiopathic pulmonary fibrosis (IPF). The investigators hypothesize that in IPF subjects who undergo single lung transplantation the administration of nintedanib 150 mg twice daily in addition to usual transplant care will result in better preservation of lung function at 24 months.

Conditions

Idiopathic Pulmonary Fibrosis; Lung Transplant; Complications

Outcome Measures

Primary Outcomes (2)

• Change in FEV1

  Change in forced expiratory volume in 1 second (FEV1)

  Baseline to 24 months

• Change in FVC

  Change in forced vital capacity (FVC)

  Baseline to 24 months

Secondary Outcomes (27)

• Bronchiolitis obliterans syndrome

  Baseline to 24 months

• Bronchial stenosis

  Baseline to 24 months

• Bronchial dehiscence

  Baseline to 24 months

• Acute cellular rejection

  Baseline to 24 months

• Drug discontinuation

  Baseline to 24 months

Study Arms (2)

Nintedanib

EXPERIMENTAL

Nintedanib 150 mg tablet by mouth twice daily for 24 months.

Drug: Nintedanib

Placebo

PLACEBO COMPARATOR

Placebo tablet by mouth twice daily for 24 months

Drug: Placebo Oral Tablet

Interventions

Nintedanib DRUG

Nintedanib (BIBF 1120, Ofev)

Also known as: BIBF 1120, Ofev

Nintedanib

Placebo Oral Tablet DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults between the ages of 35-70.
• Lung transplantation listing diagnosis of pulmonary fibrosis
• Recipient of single lung transplantation within the past 60 days

You may not qualify if:

• History of intolerability to nintedanib (i.e. discontinued nintedanib in the pre-transplant period due to adverse drug effects)
• Liver transaminase elevation (AST or ALT \> 1.5X the upper limit of normal)
• Total bilirubin \> 1.5X the upper limit of normal
• Drugs that interfere with the metabolism or elimination of nintedanib or its metabolites - St. John's wort, carbamazepine, phenytoin, rifampin, dexamethasone, and others.
• Any history of bronchial anastomosis dehiscence or stenosis
• Bleeding risk, defined as any of the following:
• Full-dose therapeutic anticoagulation (i.e. vitamin K antagonist, direct thrombin inhibitors, etc.)
• History of hemorrhagic central nervous system (CNS) event within 12 months of enrollment
• Coagulation parameters: international normalized ratio (INR) \> 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by \> 1.5X the upper limit of normal at enrollment

Sponsors & Collaborators

• Temple University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Related Publications (12)

• Thabut G, Mal H, Castier Y, Groussard O, Brugiere O, Marrash-Chahla R, Leseche G, Fournier M. Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis. J Thorac Cardiovasc Surg. 2003 Aug;126(2):469-75. doi: 10.1016/s0022-5223(03)00600-7.

  PMID: 12928646 BACKGROUND

• Lund LH, Edwards LB, Dipchand AI, Goldfarb S, Kucheryavaya AY, Levvey BJ, Meiser B, Rossano JW, Yusen RD, Stehlik J; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Heart Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016 Oct;35(10):1158-1169. doi: 10.1016/j.healun.2016.08.017. Epub 2016 Aug 21. No abstract available.

  PMID: 27772668 BACKGROUND

• Schaffer JM, Singh SK, Reitz BA, Zamanian RT, Mallidi HR. Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need. JAMA. 2015 Mar 3;313(9):936-48. doi: 10.1001/jama.2015.1175.

  PMID: 25734735 BACKGROUND

• Elicker BM, Golden JA, Ordovas KG, Leard L, Golden TR, Hays SR. Progression of native lung fibrosis in lung transplant recipients with idiopathic pulmonary fibrosis. Respir Med. 2010 Mar;104(3):426-33. doi: 10.1016/j.rmed.2009.10.019. Epub 2009 Nov 12.

  PMID: 19913395 BACKGROUND

• Wahidi MM, Ravenel J, Palmer SM, McAdams HP. Progression of idiopathic pulmonary fibrosis in native lungs after single lung transplantation. Chest. 2002 Jun;121(6):2072-6. doi: 10.1378/chest.121.6.2072.

  PMID: 12065382 BACKGROUND

• Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S, Kolb M. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015 May;45(5):1434-45. doi: 10.1183/09031936.00174914. Epub 2015 Mar 5.

  PMID: 25745043 BACKGROUND

• Xu Z, Ramachandran S, Gunasekaran M, Zhou F, Trulock E, Kreisel D, Hachem R, Mohanakumar T. MicroRNA-144 dysregulates the transforming growth factor-beta signaling cascade and contributes to the development of bronchiolitis obliterans syndrome after human lung transplantation. J Heart Lung Transplant. 2015 Sep;34(9):1154-62. doi: 10.1016/j.healun.2015.03.021. Epub 2015 Mar 27.

  PMID: 25979625 BACKGROUND

• Sjoland AA, Callerfelt AK, Thiman L, et al. Prostacyclin and VEGF in the rejection process after lung transplantation-A possible biomarker [abstract]. Eur Respir J. 2016; PA4040.

  BACKGROUND

• Suhling H, Bollmann B, Gottlieb J. Nintedanib in restrictive chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2016 Jul;35(7):939-40. doi: 10.1016/j.healun.2016.01.1220. Epub 2016 Feb 9. No abstract available.

  PMID: 26996931 BACKGROUND

• Delanote I, Wuyts WA, Yserbyt J, Verbeken EK, Verleden GM, Vos R. Safety and efficacy of bridging to lung transplantation with antifibrotic drugs in idiopathic pulmonary fibrosis: a case series. BMC Pulm Med. 2016 Nov 18;16(1):156. doi: 10.1186/s12890-016-0308-z.

  PMID: 27863518 BACKGROUND

• Dorey-Stein Z, Galli JA, Criner GJ. Effect of antifibrotic therapy in patients with idiopathic pulmonary fibrosis awaiting lung transplantation [abstract]. Am J Respir Crit Care Med. 2017;195:A5386

  BACKGROUND

• Leuschner G, Stocker F, Veit T, Kneidinger N, Winter H, Schramm R, Weig T, Matthes S, Ceelen F, Arnold P, Munker D, Klenner F, Hatz R, Frankenberger M, Behr J, Neurohr C. Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy. J Heart Lung Transplant. 2017 Jul 5:S1053-2498(17)31886-7. doi: 10.1016/j.healun.2017.07.002. Online ahead of print.

  PMID: 28734935 BACKGROUND

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jonathan A Galli, MD

  Temple University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: June 19, 2018
• Study Start: July 5, 2019
• Primary Completion: December 21, 2021
• Study Completion: December 21, 2021
• Last Updated: April 7, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)