Clinical trial NCT01059318: A Study to Determine the Safety and Effectiveness of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis
Official title: An Exploratory, Open-label, Non-randomized, Within-patient Multiple Dose-escalation Safety, Tolerability, PK and Efficacy Trial of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphangioleiomyomatosis
Keywords: Lymphangioleiomyomatosis,
High Resolution CT scan,
chest x-ray,
6 minute walk test,
pulse oximetry,
renal MRI,
Pikometer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-01-29
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was an exploratory study to determine whether escalating doses of RAD001 (everolimus) were safe and effective in patients with Lymphangioleiomyomatosis

Detailed description: In addition to the data collected in this study, historical data from 43 patients treated with placebo from the multicenter trial of sirolimus in LAM (MILES) study (NCT00414648) were down weighted to an effective sample size of 18 for comparison of FEV1 and FVC endpoints. Reference to the publication of the MILES study has been provided under "Result Publication".

Eligibility criteria: Inclusion Criteria:

* Female aged \>/= 18 years with a diagnosis of LAM
* Pulmonary function abnormalities as follows:
* FEV1 of ≤ 80% of the predicted value following administration of a standard dose of a short acting β2-agonist (\*200 µg Salbutamol, measured between 10 and 15 minutes of inhalation) OR
* FEV1 \< 90% of the predicted value of bronchodilator following administration of a standard dose of a short acting β2-agonist (\*200 µg Salbutamol, measured between 10 and 15 minutes of inhalation) and DLco (uncorrected) \<80% predicted.
* Female patients including those of childbearing potential will be included in this study.
* Negative pregnancy test at screening and baseline

Exclusion Criteria:

* FEV1\<50% of predicted post-bronchodilator.
* Change in FVC (ml) \> ± 15% of screening value at baseline visit (not less than 14d after screening visit).
* Use of any medicine containing estrogen in the 4 months prior to the screening visit and for the duration of the study
* Significant hematologic, renal, hepatic laboratory abnormality or amylase \> 1.5x the upper limit of the normal range at the screening or baseline visits
* Fasting blood glucose \> 126mg/dl or random blood glucose \>200mg/dl at screening and/or baseline
* Recent surgery (involving entry into a body cavity or requiring sutures) within 2 months of the screening visit or any evidence of unhealed surgical wound.
* Uncontrolled hyperlipidemia (defined as persistent elevation of total cholesterol or triglycerides \>6.5nM/L) or a history of clinical atherosclerotic disease including heart attack, angina, peripheral vascular disease or stroke.
* Previous organ transplantation
* Inability to give informed consent
* Inability to perform pulmonary function or 6 minute walk tests and imaging assessments

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Change From Baseline in Vascular Endothelial Growth Factor-D (VEGF-D) Concentrations
timeFrame: Baseline, 26 weeks
measure: Mean Trough (C0,ss) and Peak (C2,ss) Drug Concentration at Steady State
timeFrame: pre-dose and at 2 hour post dose at week 26
Secondary outcomes:
measure: Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: Baseline, 26 weeks
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline, 26 weeks
measure: Change From Baseline in Extended Pulmonary Function Testing
timeFrame: Baseline, 26 weeks
measure: Change From Baseline in Carbon Monoxide Diffusing Capacity (DLCO)
timeFrame: Baseline, 26 weeks
measure: Change From Baseline in 6-minute Walk Test Score to Measure Exercise Capacity
timeFrame: Baseline, 26 weeks
measure: Change From Baseline in Oxygen Saturation
timeFrame: Baseline, 26 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Center for LAM Research and Clinical Care
state: Massachusetts
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine,
state: Ohio
city: Lyon
country: France
facility: Novartis Investigative Site
city: Milan
country: Italy
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis
role: STUDY_DIRECTOR
References:
citation: McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.
citation: Goldberg HJ, Harari S, Cottin V, Rosas IO, Peters E, Biswal S, Cheng Y, Khindri S, Kovarik JM, Ma S, McCormack FX, Henske EP. Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study. Eur Respir J. 2015 Sep;46(3):783-94. doi: 10.1183/09031936.00210714. Epub 2015 Jun 25.