A Study to Determine the Effectiveness of Escalating Doses of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01059318
First received: January 28, 2010
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

This is an exploratory study. The purpose of the study is to determine whether escalating doses of RAD001 (everolimus) is safe and effective in patients with Lymphangioleiomyomatosis


Condition Intervention Phase
Lymphangioleiomyomatosis
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Assess safety, pharmacokinetics (PK) and pharmacodynamics (PD), Measure: Safety (vital signs, ECGs, safety labs, AEs), PK (concentration of everolimus), PD (serum VEGF-D) [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical efficacy of everolimus Measure: improvement in pulmonary function (FVC) [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
  • Clinical efficacy of everolimus Measure: improvement in other measures of pulmonary function (FEV-1, lung volumes (TLC, TGV, RV), DLCO) [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
  • Clinical efficacy of everolimus Measure: improvement in exercise capacity (6-minute walk test), and change in O2 saturation (with supplemental oxygen unchanged) [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: December 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 2.5mg Drug: Everolimus
Experimental: RAD001 5mg Drug: Everolimus
Experimental: RAD001 10mg Drug: Everolimus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01059318

Locations
United States, Massachusetts
Center for LAM Research and Clinical Care
Boston, Massachusetts, United States, 02115
United States, Ohio
University of Cincinnati, Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine,
Cincinnati, Ohio, United States, 45267
France
Novartis Investigative Site
Lyon, France
Germany
Novartis Investigative Site
Grosshansdorf, Germany
Novartis Investigative Site
Leipzig, Germany
Italy
Novartis Investigative Site
Milan, Italy
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01059318     History of Changes
Other Study ID Numbers: CRAD001X2201
Study First Received: January 28, 2010
Last Updated: October 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Lymphangioleiomyomatosis,
High Resolution CT scan,
chest x-ray,
6 minute walk test,
pulse oximetry,
renal MRI,
Pikometer

Additional relevant MeSH terms:
Lymphangioleiomyomatosis
Lymphangiomyoma
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Neoplasms
Perivascular Epithelioid Cell Neoplasms
Neoplasms, Connective and Soft Tissue
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 28, 2014