NCT03062943

Brief Summary

This trial is conducted locally. The aim of this trial is assess the efficacy and a favorable benefit-risk ratio for nintedanib in the treatment of LAM at the dose of 150 mg bid

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2016

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 7, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

December 6, 2016

Completed
3 months until next milestone

First Posted

Study publicly available on registry

February 24, 2017

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2021

Completed
Last Updated

September 28, 2022

Status Verified

September 1, 2022

Enrollment Period

5 years

First QC Date

October 7, 2016

Last Update Submit

September 26, 2022

Conditions

Lymphangioleiomyomatosis

Outcome Measures

Primary Outcomes (1)

  • FEV1 rate decline

    Change in FEV1 (Force Expiratory Volume in 1 second) in milliliters per month. The FEV1 slope will be calculated at baseline and at 3, 6, 9 and up to 12 months during the treatment phase.

    up to 12 months

Secondary Outcomes (1)

  • Safety and Tolerability in terms of AEs, particularly for liver function and level of hepatic enzymes.

    up to 12 months

Study Arms (1)

Nintedanib 150mg BID

EXPERIMENTAL

nintedanib soft gelatine capsules Dose: 150 mg bid Mode of admin. : Oral Duration of treatment: 1 year Duration of follow-up: 12 months after treatment discontinuation

Drug: Nintedanib

Interventions

NintedanibDRUG
Also known as: OFEV
Nintedanib 150mg BID

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written Informed Consent for participating to trial.
  • Patient aged ≥ 18 years at visit 1.
  • Sporadic or TSC associated LAM, classified as ''definite'' by the European Respiratory Society criteria and /or serum VEGFD level \>/= 800 mg/ml, and evidence of a 10% deterioration in FEV1 and /or loss of 80 ml of FEV1 or more in the last year (post bronchodilator). Also LAM patients with proven side effects and/or toxicities/ contraindications to sirolimus therapy will be eligible for this study.

You may not qualify if:

  • Laboratory parameters have to satisfy entry criteria as shown below:
  • Laboratory parameters (screening)
  • AST, ALT \> 1.5 x ULN
  • Bilirubin \> 1.5 x ULN
  • Positivity for HIV or Hepatitis.
  • Chylous effusions.
  • Relapsing pneumothorax.
  • Angiomyolipoma \> 5 cm.
  • Treatment with mTOR inhibitors in the last month.
  • Patient eligible for Lung Transplantation.
  • Hormone therapy.
  • Patients are excluded if they are post lung transplant or had previously been diagnosed with a pneumothorax, chylous effusion, bleeding angiomyolipoma within the previous 6 months.
  • Current smokers.
  • Other diseases:
  • Cardiac disease.
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Pneumology unit

Milan, 20123, Italy

Location

Related Publications (5)

  • Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell. 2005 Apr 22;121(2):179-93. doi: 10.1016/j.cell.2005.02.031.

    PMID: 15851026BACKGROUND

  • Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014 May;349(2):209-20. doi: 10.1124/jpet.113.208223. Epub 2014 Feb 20.

    PMID: 24556663RESULT

  • Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002 Sep;4(9):648-57. doi: 10.1038/ncb839.

    PMID: 12172553RESULT

  • Crino L, Metro G. Therapeutic options targeting angiogenesis in nonsmall cell lung cancer. Eur Respir Rev. 2014 Mar 1;23(131):79-91. doi: 10.1183/09059180.00008913.

    PMID: 24591665RESULT

  • Harari S, Elia D, Caminati A, Geginat J, Luisi F, Pelosi G, Specchia C, Torre O, Trevisan R, Vasco C, Zompatori M, Cassandro R. Nintedanib for patients with lymphangioleiomyomatosis: a phase 2, open-label, single-arm study. Lancet Respir Med. 2024 Dec;12(12):967-974. doi: 10.1016/S2213-2600(24)00217-0. Epub 2024 Oct 25.

    PMID: 39489895DERIVED

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

nintedanib

Condition Hierarchy (Ancestors)

LymphangiomyomaNeoplasm, Lymphatic TissueNeoplasms by Histologic TypeNeoplasmsPerivascular Epithelioid Cell NeoplasmsNeoplasms, Connective and Soft TissueLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Sergio A Harari, MD

    MultiMedica - San Giuseppe Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 7, 2016

First Posted

February 24, 2017

Study Start

December 6, 2016

Primary Completion

December 1, 2021

Study Completion

December 1, 2021

Last Updated

September 28, 2022

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)