A pilot study of nintedanib for lymphangioleiomyomatosis (LAM)

• Register: EUCTR
• Last refreshed on: 16 August 2016
• Main ID: EUCTR2015-004919-20-IT
• Date of registration: 11/08/2016
• Prospective Registration: No
• Primary sponsor: MULTIMEDICA S.P.A.
• Public title: A pilot study of nintedanib for lymphangioleiomyomatosis (LAM)
• Scientific title: A pilot study of nintedanib for lymphangioleiomyomatosis (LAM) - A pilot study of nintedanib for lymphangioleiomyomatosis (LAM)
• Date of first enrolment: 09/03/2016
• Target sample size: 30
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004919-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Hystorical control group (MILES trial) If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: NA- No Comparator Number of treatment arms in the trial: 0
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Name: Servizio di Data Management
• Affiliation: MultiMedica SpA

• Name: Servizio di Data Management
• Affiliation: MultiMedica SpA

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written Informed Consent for participating to trial e to genetic tests,
2. Patient aged = 18 years at visit 1,
3. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
Previous treatment with nintedanib
Other investigational therapy (participation in research trial) received within 8 weeks of visit
Thoracic, abdominal, gynecological, neurologic surgical procedures planned to occur during
trial period.
Pregnant women or women who are breast feeding or of child bearing potential not using
two effective methods of birth control (one barrier and one highly effective non-barrier) for
at least 1 month prior to enrolment (and until 3 months after treatment end).
Female patients will be considered to be of childbearing potential unless surgically sterilised
by hysterectomy or bilateral tubal ligation, or postmenopausal for at least two years or if
women use a barrier method of contraception includes condom or occlusive cap with
spermicidal (foam, gel, film, cream, suppository) or male sterilization (with appropriate
post-vasectomy documentation of the absence of sperm in the ejaculate), or if they use an
intrauterine device
· International normalized ratio (INR) > 2 at visit 1


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Female subjects affected by Llymphangioleiomyomatosis (LAM)
MedDRA version: 19.0 Level: PT Classification code 10049459 Term: Lymphangioleiomyomatosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Ofev
Pharmaceutical Form: Capsule, soft

Primary Outcome(s)

Secondary Objective: Functional respiratory evaluation after treatment compared to basal
- Safety and tolerability
- FVC variation compared to basal
- DLCO variation compared to basal
- Serum VEGF-D variation compared to basal
- Efficacy of Nintedanib in angiomyolipoma size reduction (in patients with angiomyolipomas not greater than 5 cm of diameter).
- Efficacy of Nintedan

Main Objective: The primary objective is to demonstrate a reduction of lung function decline, as measured by a
change of the yearly rate of decline of FEV1

Primary end point(s): The primary outcome measure will be the FEV1 response, which will be assessed as the change in FEV1 (FEV1 slope) in milliliters per month ( post bronchodilator).

Timepoint(s) of evaluation of this end point: 12 and 18 months

Secondary Outcome(s)

Secondary end point(s): The proportion of patients achieving a stabilization of the lung function during treatment. A patient will be considered stabilized if her value of the FEV1 measured at 12-month visit will be equal or above the baseline value. - Safety and Tolerability - Rate of decline of FVC over the course of the study - Rate of decline Dlco over the course of the study over the course of the study -VEGF-D levels: change from baseline at the end of treatment period - To assess if nintedanib can reduce renal angiomyolipomas (presence determined from MRI and defined as lesions with a maximum diameter of a least 1 cm). Reduction is defined as a decrease of total volume of target angiomyolipomas (sum of volume of all target lesions indentified at baseline) of at least 30% relative to baseline. New angiomyolipoma = 1 cm in diameter, kidney increases in volume > 20%, and angiomyolipoma related bleeding must be excluded. - To test if nintedanib reduces the number of circulating LAM cells in treated pts and if the loss of circulating LAM cells persists after treatment discontinuation. - Quality of

Timepoint(s) of evaluation of this end point: 12 and 18 months

Secondary ID(s)

StudioLAM

Source(s) of Monetary Support

B.4.1 Azienda Farmaceutica: Boehringer Ingelheim Pharma GmbH &Co. KG