Lymphangioleiomyomatosis MedDRA version: 12.1 Level: LLT Classification code 10049459 Term: Lymphangioleiomyomatosis
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical Form:
Sponsors
NOVARTIS FARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female aged 18 years or older with a diagnosis of LAM as determined by either of the following: a. Lung biopsy and chest HRCT scan with findings compatible with LAM or b. Typical clinical syndrome and chest HRCT scan findings compatible with LAM in plus c. one or more of the following: -CT or histological evidence of renal angiomyolipoma or -Chylous pleural or abdominal collection or -Abdominal / pelvic lymphangioleiomyoma or -Characteristic HRCT scan and clinical syndrome compatible with an established genetic diagnosis of tuberous sclerosis complex (using revised diagnostic criteria). 2. Pulmonary function abnormalities as follows: a. Forced expiratory volume in one second (FEV1) of = 80% of the predicted value following administration of a standard dose of a short acting ß2-agonist (*200 µg Salbutamol, measured between 10 and 15 minutes of inhalation) OR b. FEV1 40 IU/L at screening, or b. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF, or c. Two forms of barrier contraception (e.g., condom and occlusive cap plus spermicide), or d. If female subject has a male partner who has undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing, or e. The subject must abstain from vaginal intercourse for the entire duration of the study” f. The male partners of female patients must refrain from fathering a child for at least 8 weeks following the last study drug administration. 4. All female patients must have negative pregnancy test results at screening and at baseline. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. WHO class IV functional status. 2. FEV1 ? 15% of screening value at baseline visit (not less than 14d after screening visit). FVC measurement performed at least two weeks and at most 13 weeks prior to the screening visit could also be used to assess stability using the same ? 15% criterion. Despite the possible use of historical data, FVC will still be measured at screening and baseline as per the assessment schedule. 4. Listed for organ transplantation and on active status. 5. Use of Sirolimus (Rapamycin™) in the 4 months prior to the screening visit and for the duration of the study 6. Use of doxycycline or other tetracycline derivatives within 30 days prior to the screening visit and for the duration of the study 7. Use of an investigational drug within the last 30 days prior to the screening visit 8. Use of any medicine containing estrogen in the 4 months prior to the screening visit and for the duration of the study 9. Use of alternative or complimentary medications within 30 days prior to the screening visit and for the duration of the study 10. Use of antibiotics or a clinical history consistent with bacterial infection in the 30 days prior to study entry 11. Pregnant or breast feeding 12. Significant hematologic (Hemoglobin 2 mg/dl) , hepatic laboratory abnormality (transaminase levels > three times the upper limit of normal range) or amylase > 1.5x the upper limit of the normal range at the screening or baseline visits 13. Fasting blood glucose > 126mg/dl or random blood glucose >200mg/dl at screening and/or baseline 14. 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. 15. 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. 16. Any type of pleural disease severe enough to affect pulmonary function as determined by the site investigator. 17. History of acute pneumothorax or chylothorax within 2 months of the screening visit 18. Previous organ transplantation 19. Inability to attend scheduled clinic visits 20. Inability to give informed consent 21. Inability to perform pulmonary function or 6 minute walk tests and imaging assessments 22. History of malignancy in the two years prior to the screening visit, other than squamous or basal cell skin cancer, angiomyolipoma or menigioma. 23. Any other reason that the investigator feels that the subject would not be able to adequately perform the procedures necessary for study participation or that may put patient at risk from participating in the trial. 24. Contraindications to MRI: a. Brain Aneurysm Clip b. Implanted neural stimulator c. Implanted cardiac pacemaker, pacemaker wires or defibrillator d. Prosthetic heart valves e. Cochlear implant f. Ocular foreign body (e.g. metal shavings) g. Other implanted medical devices: (e.g. Swan Ganz catheter) h. Implanted insulin pump i. Metal shrapnel or bullet.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD, assessed by serum VEGF-D) of everolimus in patients with lymphangioleiomyomatosis (LAM).;Secondary Objective: The key secondary objectives are: - to assess the clinical efficacy of everolimus as measured by improvement in pulmonary function (FVC). - to assess the efficacy of everolimus as measured by improvement in other measures of pulmonary function (FEV-1, lung volumes (TLC, TGV, RV), DLCO). - to assess the efficacy of everolimus as measured by improvement in exercise capacity (6-minute walk test), and change in O2 saturation (with supplemental oxygen unchanged). For exploratory objectives, please refer to the protocol.;Primary end point(s): To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD, assessed by serum VEGF-D) of everolimus in patients with lymphangioleiomyomatosis (LAM). | — |
Countries
France, Italy
Outcome results
None listed