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LymphangioleiomyomatosisPhase 2NCT01059318

A Study to Determine the Safety and Effectiveness of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis

A Phase 2 study testing Everolimus in people with Lymphangioleiomyomatosis, run by Novartis Pharmaceuticals at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This was an exploratory study to determine whether escalating doses of RAD001 (everolimus) were safe and effective in patients with Lymphangioleiomyomatosis Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Lymphangioleiomyomatosis
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
4 sitesin 3 countries
Study dates
Jan 2010to Jun 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 11Show fewer
  • 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

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

United States2 sites

  • Center for LAM Research and Clinical Care

    Boston, Massachusetts, 02115

  • University of Cincinnati, Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine,

    Cincinnati, Ohio, 45267

Other trials in United States

France1 site

  • Novartis Investigative Site

    Lyon

Other trials in France

Italy1 site

  • Novartis Investigative Site

    Milan

Other trials in Italy

About this study

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

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

Read the 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".

Being tested
Everolimus
Keywords
Lymphangioleiomyomatosis,, High Resolution CT scan,, chest x-ray,, 6 minute walk test,, pulse oximetry,, renal MRI,, Pikometer
Medical subject headings
Lymphangioleiomyomatosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called RAD001

    Everolimus was formulated as tablets in strengths of 2.5mg, 5mg and 10mg.

Study groups in NCT01059318
Study groupRoleWhat they receive
EverolimusExperimentalAll patients received a starting dose of everolimus 2.5mg/day for 4 weeks, followed by a dose of 5 mg/day for 4 weeks and finally a dose of 10mg/day for 18 weeks. The 26 week treatment period was followed by an optional extension period wherein patients continued therapy until the last patient had completed 26-weeks of treatment. The longest period a patient participated in the study was 62 weeks.
Receives: Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Vascular Endothelial Growth Factor-D (VEGF-D) Concentrations

    Blood samples (1 mL) for determination of VEGF-D were collected from a forearm vein (direct venipuncture or from an indwelling cannula) and 2 aliquots of serum were collected. VEGF-D levels were determined from only 1 of the 2 serum aliquots, with the second acting as a back-up. A serum VEGF-D >800 pg/mL level supports a diagnosis of Lymphangioleiomyomatosis (LAM)

    Measured: Baseline, 26 weeks

  2. Mean Trough (C0,ss) and Peak (C2,ss) Drug Concentration at Steady State

    Venous blood samples (2 mL) for pharmacokinetic evaluation were collected pre dose and 2 hours post dose at preselected visits.

    Measured: pre-dose and at 2 hour post dose at week 26

Secondary outcomes (6)

  1. Change From Baseline in Forced Vital Capacity (FVC)

    All spirometry evaluation followed recommendations of the Standardization of Lung Function Testing. All spirometry maneuvers were performed in sitting position whilst wearing nose clips. At least three acceptable maneuvers were performed for each time point, and results met within-test and between-test criteria for acceptability. The highest value was obtained of FVC from any of the three maneuvers that met acceptability criteria. Change from baseline in FVC was compared between everolimus and historical placebo data from multicenter trial of sirolimus in LAM. (MILES NCT00414648) due to absence of placebo group in this current study on a rare lung disease. These two studies had different study designs, so the change from baseline to 6 months (26 weeks) in MILES study was estimated from the publicly reported rate of change per month to provide a meaningful comparison. This historical control be can be viewed on the Novartis Clinical Trial Results website.

    Measured: Baseline, 26 weeks

  2. Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)

    All spirometry evaluation followed the recommendations of the Standardization of Lung Function Testing. All spirometry maneuvers were performed in the sitting position whilst wearing nose clips. At least three acceptable maneuvers were performed for each time point, and the results met within-test and between-test criteria for acceptability. The highest value was obtained of FEV1 from any of the three maneuvers that met acceptability criteria.

    Change from baseline in FEV1 was compared between everolimus and historical placebo data from the MILES study (NCT00414648) due to the absence of a placebo group in this current study on a rare lung disease. These two studies had different study designs, so the change from baseline to 6 months (26 weeks) in MILES study was estimated from the publicly reported rate of change per month in order to provide a meaningful comparison. This historical control can be viewed on the Novartis Clinical Trial Results website.

    Measured: Baseline, 26 weeks

  3. Change From Baseline in Extended Pulmonary Function Testing

    Extended pulmonary function testing such as Total Lung Capacity (TLC), Thoracic Gas Volume (TGV), Residual Volume (RV) were measured using a body plethysmograph

    Measured: Baseline, 26 weeks

  4. Change From Baseline in Carbon Monoxide Diffusing Capacity (DLCO)

    Carbon Monoxide Diffusing Capacity (DLCO) one of the extended pulmonary function testing which was also measured using a body plethysmograph.

    Measured: Baseline, 26 weeks

  5. Change From Baseline in 6-minute Walk Test Score to Measure Exercise Capacity

    A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The test was done about the same time of day to avoid diurnal variation in an environment that had an adequate temperature to avoid additional burden to the patient due to heat or cold air. The distance walked in six minutes (6MWD) was recorded.

    Measured: Baseline, 26 weeks

  6. Change From Baseline in Oxygen Saturation

    Oxygen saturation means the amount of oxygen in blood stream. Oxygen saturation was measured by using a Pulse Oximeter.

    Measured: Baseline, 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2010 (estimated)
  2. Study startJan 2010
  3. Primary completionJun 2012
  4. Study completionJun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01059318
Sponsor's protocol ID
CRAD001X2201
Other IDs
2010-019825-32
Status last verified
Oct 2020
First submitted
28 Jan 2010
Last updated
19 Nov 2020

Publications

  • 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.

    PubMed 21410393

  • 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.

    PubMed 26113676

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus in people with Lymphangioleiomyomatosis, run by Novartis Pharmaceuticals at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, France, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Vascular Endothelial Growth Factor-D (VEGF-D) Concentrations (time frame: Baseline, 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01059318, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020.

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