A Randomized, Double-blind, Placebo-controlled Study of Everolimus in the Treatment of Patients With Subependymal Giant Cell Astrocytomas (SEGA) Associated With Tuberous Sclerosis Complex (TSC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 13
- 主要终点
- Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response
研究概览
简要总结
This study evaluated the efficacy and safety of Everolimus in treating patients with Subependymal Giant Cell Astrocytomas associated with Tuberous Sclerosis Complex.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Definite diagnosis of Tuberous Sclerosis according to the modified Gomez criteria
- •At least one Subependymal Giant Cell Astrocytoma of at least 1 cm in diameter
- •Evidence of SEGA worsening as compared to prior MRI scans
- •Females of child bearing potential must use birth control
- •Written informed consent
排除标准
- •SEGA related surgery is likely to be required in the opinion of the investigator
- •Recent heart attack, cardiac related chest pain or stroke
- •Severely impaired lung function
- •Severe liver dysfunction
- •Severe kidney dysfunction
- •Pregnancy or breast feeding
- •Current infection
- •History of organ transplant
- •Surgery within two months prior to study enrollment
- •Prior therapy with a medication in the same class as Everolimus
- •Uncontrolled high cholesterol
- •Uncontrolled diabetes
- •Patients with metal implants thus prohibiting MRI evaluations
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Everolimus
Everolimus was administered orally at a starting dose of 4.5mg/m^2 daily and subsequently titrated to attain whole blood trough concentration of 5 to 15 ng/mL. Dose adjustments were permitted based on safety and whole blood trough concentrations.
干预措施: Everolimus (Drug)
Placebo
Matching Placebo administered orally.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response
时间窗: End of core period (Week 48), and end of extension period (up to 4 years)
Participants were assessed for SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilized to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.
次要结局
- Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period(Baseline (Core period) to Week 24 (Core period), Baseline (Extension period, Week 24 post-core baseline) to Week 24 (Extension period, Week 48 post-core baseline))
- Time to SEGA Progression(Baseline up to week 48 (end of core period), and end of extension period (up to 4 years))
- Time to SEGA Worsening(Baseline up to week 48 (end of core period), and end of extension period (up to 4 years))
- Duration of Skin Lesion Response in Everolimus Treated Participants(Baseline up to week 48 (end of core period), and end of extension period (up to 4 years))
- Everolimus Blood Concentration (C2h) at 2 Hours Post Dose(2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240)
- Time to SEGA Response(Baseline up to week 48 (end of core period), and end of extension period (up to 4 years))
- Duration of SEGA Response(Baseline up to week 48 (end of core period), and end of extension period (up to 4 years))
- Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score(End of core period (Week 48), and end of extension period (up to 4 years))
- Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose(24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240)
- Percentage of Participants With Renal Impairment During Core Period(Day 1 up to 28 days after end of treatment (Core period))