NCT00916747进行中（未招募）2 期
An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- To evaluate the therapeutic effects of the combination of zoledronic acid, pravastatin and lonafarnib in patients with HGPS.
研究概览
简要总结
Hutchinson-Gilford Progeria Syndrome (Progeria) is a rare autosomal disease that results in premature death at a median age of 13 years due to cardiovascular and cerebralvascular compromise. The mutation for this disease has been identified and results in a mutant form of lamin A that cannot be de-farnesylated. This study evaluates the combination of pravastain (a statin), lonafarnib (a farnesyltransferase inhibitor) and zoledronic acid (a bisphosphonate) in an open label phase II efficacy trial in children with Progeria. These agents all target farnesylation pathways at different points. Patients with genetically confirmed progeria will be eligible for this protocol. Treatment will be initiated for 24 months duration. Clinical and biologic parameters will be examined to assess response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetic Diagnosis: All patients must have confirmatory mutational analysis showing mutation in the lamin A gene.
- •Clinical Diagnosis: Patients must display clinical signs of progeria as per the clinical trial team.
- •Travel: Patients must be willing and able to come to Boston for appropriate studies and examinations at initiation of study and at months 6, 12, 18 and 24 on study.
- •Patient must have adequate organ and marrow function as defined by the following parameters:
- •Blood: APC (ANC + bands + monocytes = APC) > 1,000/microliters, Platelets > 75,000/microliters (transfusion independent); Hemoglobin >9g/dl.
- •Renal: creatinine Less than or equal 1.5 times normal for age or GFR > 70 ml/min/1.73m
- •Hepatic: bilirubin Less than or equal to 1.5 x upper limit of normal for age; SGPT (ALT) < and SGOT (AST) < 5 x normal range for age.
- •PT/PTT: PT/PTT < 120% upper limit of normal OR PI approval
- •No overt renal, hepatic, pulmonary disease or immune dysfunction.
- •25-hydroxyvitamin D ≥ 20 ng/ml within 4 weeks of bisphosphonate infusion.
- •Signed informed consent according to institutional guidelines must be obtained and patient must begin therapy within twenty eight (28) days.
排除标准
- •Other than the drugs used in this protocol, drugs targeted to treat Progeria are excluded. Drugs to treat symptoms of Progeria are permitted.
- •Patients must not be taking medications that significantly affect the metabolism of lonafarnib at the time they start lonafarnib
- •Patient must have no uncontrolled infection.
- •Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated.
- •Patients must not be pregnant or breast-feeding. Female patients of childbearing potential must have negative serum or urine pregnancy test. Male and female patients of reproductive potential must agree to use a medically accepted form of birth control while on study and up to 10 weeks after treatment. It is permissible for female patients to take oral contraceptives or other hormonal methods while receiving treatment with lonafarnib.
研究组 & 干预措施
Treatment arm
Experimental
All patients will receive zoledronic acid, pravastatin and lonafarnib
干预措施: Lonafarnib, Zoledronic Acid, and Pravastatin (Drug)
结局指标
主要结局
To evaluate the therapeutic effects of the combination of zoledronic acid, pravastatin and lonafarnib in patients with HGPS.
时间窗: 2 years
次要结局
- To describe any acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib.(2 years)
- To investigate which clinical and laboratory studies are needed to monitor or alter therapy to prevent unacceptable toxicity.(2 years)
- To assess the pharmacokinetics of lonafarnib in patients with progeria.(2 years)
- To assay for the inhibition of HDJ-2 farnesylation in Peripheral Blood Leukocytes (PBL).(2 years)
- To compare and incorporate clinical and laboratory data obtain from this study with that obtained during the single agent lonafarnib trial as well as the pilot combination trial of zoledronic acid, pravastatin and lonafarnib(2 years)
- To assay for changes in research-based potential markers of efficacy such as levels of prelamin A, mature lamin A, progerin, and HP1 in protein isolated from PBL.(2 years)
- To assess changes in leptin levels, glucose utilization, skeletal abnormalities including bone mineral density and X-ray finding, joint contracture and function, and growth(2 years)
- To assess changes in auditory function, dental anomalies, dermatologic changes including hair density, nutrition with calorie analysis and energy expenditure, body composition analysis by DXA scan, and cardiovascular structure and function.(2 years)
研究者
Monica E. Kleinman
Principal Investigator
Boston Children's Hospital
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Treatment of the Hutchinson-Gilford Progeria Syndrome With a Combination of Pravastatin and Zoledronic AcidHutchinson-Gilford Progeria SyndromeNCT00731016Assistance Publique Hopitaux De Marseille15
已完成
3 期
Efficacy of Zoledronic Acid in Preventing Collapse of the Osteonecrotic Femoral HeadAvascular Necrosis of Femoral HeadNCT00939900Seoul National University Bundang Hospital110
终止
2 期
Adjuvant Zoledronic Acid in High Risk Giant Cell Tumour of Bone (GCT)Giant Cell Tumor of BoneOsteoclastomaNCT00889590Leiden University Medical Center15
已完成
3 期
Study of Zoledronic Acid for Patients With Hormone-sensitive Bone Metastases From Prostate CancerProstate CancerNCT00242567Novartis Pharmaceuticals522
招募中
1 期
Phase 1/2 Study of CAN103 in Subjects With Gaucher DiseaseGaucher Disease, Type 1Gaucher Disease, Type 3NCT05447494CANbridge (Suzhou) Bio-pharma Co., Ltd.40