A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
Overview
- Phase
- Phase 3
- Intervention
- Everolimus (RAD001)
- Conditions
- Tuberous Sclerosis Complex (TSC)
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 118
- Locations
- 7
- Primary Endpoint
- Angiomyolipoma Response Rate as Per Central Radiology Review
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or Female 18 years or older
- •Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)
- •Clinically definite diagnosis of renal angiomyolipoma
- •At least one Angiomyolipoma of ≥ 3 cm in its longest diameter using CT or MRI
- •Females of child bearing potential must use birth control and have documentation of negative pregnancy test
- •Written informed consent according to local guidelines
Exclusion Criteria
- •Recent heart attack, cardiac related chest pain or stroke
- •Severely impaired lung function
- •Bleeding related to angiomyolipoma or embolization during 6 months prior to randomization
- •Clinically significant chylous ascites
- •Clinically significant hematological or hepatic abnormality
- •Severe liver dysfunction
- •Severe kidney dysfunction
- •Pregnancy or breast feeding
- •Current infection
- •History of organ transplant
Arms & Interventions
Everolimus
Study drug was given by continuous oral daily dosing of two 5 mg tablets.
Intervention: Everolimus (RAD001)
Placebo
Placebo was given by continuous oral daily dosing of two 5 mg tablets.
Intervention: Everolimus Placebo
Outcomes
Primary Outcomes
Angiomyolipoma Response Rate as Per Central Radiology Review
Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume \> 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
Secondary Outcomes
- Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years)
- Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker(4 weeks, 12 weeks, 24 weeks, 36 weeks 48 weeks, 60 weeks, 72 weeks)
- Everolimus Trough Concentrations (Cmin)(Prior to dosing at weeks 2, 4, 12, 24, 48)
- Time to Angiomyolipoma Progression as Per Central Radiology Review(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years)
- Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose(2 hours post-dose administration at Weeks 2, 4, 12, 24, 48)
- Percentage of Participants With Renal Impairment(Day 1 up to 28 days after end of treatment)
- Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years)
- Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years)
- Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR)(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years)