A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
Tracking Information | |
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First Received Date ICMJE | April 8, 2009 |
Last Updated Date | April 20, 2010 |
Start Date ICMJE | March 2009 |
Primary Completion Date | April 2009 (final data collection date for primary outcome measure) |
Current Primary Outcome Measures ICMJE |
The primary objective of this study is to evaluate the feasibility of administering intravenous zoledronic acid, oral pravastatin and oral lonafarnib, to patients with Progeria for a minimum of 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ] |
Original Primary Outcome Measures ICMJE | Same as current |
Change History | Complete list of historical versions of study NCT00879034 on ClinicalTrials.gov Archive Site |
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current |
Current Other Outcome Measures ICMJE | |
Original Other Outcome Measures ICMJE | |
Descriptive Information | |
Brief Title ICMJE | A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria |
Official Title ICMJE | A Phase II Pilot Study of Zoledronic Acid, Pravastatin, and Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathies |
Brief Summary | Progerias are rare "premature aging" diseases in which children die of severe atherosclerosis leading to strokes and heart attacks. It is a multisystem disease with objective clinical markers for disease progression. These include abnormalities in growth and body composition, bone mineral density, join function, endocrine function, alopecia, and vascular disease. There is currently no therapy proven effective for any of the progressive and deleterious aspects of this disorder. Progeria is caused by a gene defect in the gene LMNA, coding for the nuclear protein lamin A. Lamin A is normally expressed by most differentiated cells, and requires posttranslational farnesylation to incorporate into the nuclear membrane. This trial proposes to use three agents (zoledronic acid, pravastatin, and lonafarnib) to inhibit farnesylation of abnormal lamin, the disease causing protein in Progeria. The primary objective of this study is to evaluate the feasibility of administering intravenous zoledronic acid, oral pravastatin and oral lonafarnib, to patients wtih Progeria for a minimum of 4 weeks. |
Detailed Description | This is an open label single arm feasibility trial. A combination of two oral agents (pravastatin and lonafarnib) and one intravenous (IV) agent (zoledronic acid) will be administered at doses and schedule currently applied in pediatrics. These agents all target farnesylation pathways at different points. Our goal is to inhibit farnesylation of abnormal lamin, the disease-causing protein in Hutchinson-Gilford Progeria Syndrome and progeroid laminopathies (henceforth "progeria"). The drugs will include the intravenous bisphosphonate zoledronic acid, oral HMG co-reductase inhibitor pravastatin and the oral farnesyltransferase inhibitor (FTI) lonafarnib (SCH 66336). Patients with genetically confirmed progeria will be eligible for this protocol. Treatment will be initiated for 4 weeks duration and may be extended depending on tolerability. This study will assess the feasibility of this treatment regimen in the first 4 weeks. If tolerated for 4 weeks, patients can be treated with this regimen for up to 6 months. |
Study Type ICMJE | Interventional |
Study Phase | Phase 2 |
Study Design ICMJE | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
Condition ICMJE | Progeria |
Intervention ICMJE |
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Study Arm (s) | |
Publications * | |
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |
Recruitment Status ICMJE | Completed |
Estimated Enrollment ICMJE | 5 |
Completion Date | April 2009 |
Primary Completion Date | April 2009 (final data collection date for primary outcome measure) |
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both |
Ages | |
Accepts Healthy Volunteers | No |
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects |
Location Countries ICMJE | United States |
Administrative Information | |
NCT Number ICMJE | NCT00879034 |
Other Study ID Numbers ICMJE | 09-02-0074 |
Has Data Monitoring Committee | Yes |
Responsible Party | Mark Kieran, M.D, Ph.D, Children's Hosptial Boston/ Dana-Farber Cancer Institute |
Study Sponsor ICMJE | Children's Hospital Boston |
Collaborators ICMJE |
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Investigators ICMJE | |
Information Provided By | Children's Hospital Boston |
Verification Date | April 2010 |
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |