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Trial record 6 of 9 for:    progeria

A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria

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ClinicalTrials.gov Identifier: NCT00879034
Recruitment Status : Completed
First Posted : April 9, 2009
Results First Posted : July 31, 2017
Last Update Posted : June 13, 2019
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Schering-Plough
Information provided by (Responsible Party):
Monica E. Kleinman, Boston Children's Hospital

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Progeria
Hutchinson-Gilford Syndrome
Interventions Drug: Lonafarnib
Drug: Zoledronic Acid
Drug: Pravastatin
Enrollment 5
Recruitment Details 4 patients with classic HGPS from the United States were enrolled in March 2009 at Boston Children's Hospital. 1 additional patient had nonclassic mutations.
Pre-assignment Details All patients screened to participate in study were consented onto the study as planned.
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Period Title: Overall Study
Started 5
Received Treatment [1] 4
Completed 5
Not Completed 0
[1]
One patient did not receive a zoledronic acid infusion during study.
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
5
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
1
  20.0%
Male
4
  80.0%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants
5
1.Primary Outcome
Title 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
Hide Description Feasibility was assessed by determining the number of participants with adverse events occurring over the course of the 4 week study.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Results are reported for the 5 patients who completed the 4 weeks of therapy.
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description:
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Secondary Outcome
Title To Describe Any Acute and Chronic Toxicities Associated With Treating Progeria Patients With the Combination of Zoledronic Acid, Pravastatin and Lonafarnib
Hide Description Number of participants with acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description:
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Secondary Outcome
Title To Investigate Which Clinical and Laboratory Studies Are Needed to Monitor or Alter Therapy to Prevent Unacceptable Toxicity
Hide Description The number of participants with abnormal CBC w/diff panel, LFTs, renal functions and lipid panels.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description:
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
4.Secondary Outcome
Title To Assess the Pharmacokinetics of Lonafarnib in Patients With Progeria.
Hide Description [Not Specified]
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for this feasibility study. Pharmacokinetics assessment of lonafarnib in these 5 patients was analyzed at the end of a different protocol, NCT00916747.
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description:
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title To Assay for the Inhibition of HDJ-2 Farnesylation in Peripheral Blood Leukocytes (PBL)
Hide Description [Not Specified]
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for this feasibility study. HDJ-2 assessment in these 5 patients was analyzed at the end of a different protocol, NCT00916747.
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description:
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title 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.
Hide Description The number of participants from whom baseline clinical and Laboratory data was obtained.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description:
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
5
 100.0%
Time Frame Up to 4 weeks. Assessed at week 0 and week 4.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Zoledronic Acid, Pravastatin, and Lonafarnib
Hide Arm/Group Description Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
All-Cause Mortality
Zoledronic Acid, Pravastatin, and Lonafarnib
Affected / at Risk (%)
Total   0/5 (0.00%) 
Hide Serious Adverse Events
Zoledronic Acid, Pravastatin, and Lonafarnib
Affected / at Risk (%)
Total   0/5 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Zoledronic Acid, Pravastatin, and Lonafarnib
Affected / at Risk (%)
Total   0/5 (0.00%) 
This was an open label clinical trial on a very rare disease population. Patient numbers are small, though 5 participants represents a small but significant portion of the world's population of children with HGPS.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mark Kieran
Organization: Dana-Farber Cancer Institute
Phone: 617-632-4907
EMail: mark_kieran@dfci.harvard.edu
Layout table for additonal information
Responsible Party: Monica E. Kleinman, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT00879034    
Other Study ID Numbers: 09-02-0074
P06087 ( Other Identifier: Schering-Plough )
First Submitted: April 8, 2009
First Posted: April 9, 2009
Results First Submitted: May 24, 2017
Results First Posted: July 31, 2017
Last Update Posted: June 13, 2019