Phase 2
N=5
A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
Progeria · Hutchinson-Gilford Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT00879034 ↗Enrolled (actual)
5
Serious AEs
0.0%
Results posted
Jul 2017
Primary outcome: Primary: 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 — 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lonafarnib (Drug); Zoledronic Acid (Drug); Pravastatin (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Boston Children's Hospital
- Primary completion
- Apr 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
— | — |
| SECONDARY To Describe Any Acute and Chronic Toxicities Associated With Treating Progeria Patients With the Combination of Zoledronic Acid, Pravastatin and Lonafarnib |
— | — |
| SECONDARY To Investigate Which Clinical and Laboratory Studies Are Needed to Monitor or Alter Therapy to Prevent Unacceptable Toxicity |
— | — |
| SECONDARY To Assess the Pharmacokinetics of Lonafarnib in Patients With Progeria. |
— | — |
| SECONDARY To Assay for the Inhibition of HDJ-2 Farnesylation in Peripheral Blood Leukocytes (PBL) |
— | — |
| SECONDARY To Obtain Baseline Clinical and Laboratory Data so That Longer-term Measures of Efficacy Will be Achievable if Treatment Continues Beyond the 4-week Feasibility Study Period. |
5 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- Genetic Diagnosis: All patients must have confirmatory mutational analysis showing mutation in the lamin A gene.
- Patients must display clinical signs of progeria as per the clinical trial team.
- Patients must be willing and able to come to Boston for appropriate studies and examinations at initiation of study and at week 4 of study.
- Patient must have adequate organ and marrow function as defined by study parameters
Exclusion Criteria
- Other than the drugs used in this protocol, other 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 pregnancy of 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.
Data sourced from ClinicalTrials.gov (NCT00879034). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.