Clinical Trial: Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional
Official Title: An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies
Brief Summary: 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.
Detailed Summary:
Sponsor: Boston Children’s Hospital
Current Primary Outcome: To evaluate the therapeutic effects of the combination of zoledronic acid, pravastatin and lonafarnib in patients with HGPS. [ Time Frame: 2 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- To describe any acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib. [ Time Frame: 2 years ]
- To investigate which clinical and laboratory studies are needed to monitor or alter therapy to prevent unacceptable toxicity. [ Time Frame: 2 years ]
- To assess the pharmacokinetics of lonafarnib in patients with progeria. [ Time Frame: 2 years ]
- To assay for the inhibition of HDJ-2 farnesylation in Peripheral Blood Leukocytes (PBL). [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 2 years ]
Original Secondary Outcome: Same as current
Information By: Boston Children’s Hospital
Dates:
Date Received: June 5, 2009
Date Started: August 2009
Date Completion: June 2017
Last Updated: April 14, 2017
Last Verified: April 2017
