Trial Outcomes & Findings for A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria (NCT NCT00879034)

Results Overview

Feasibility was assessed by determining the number of participants with adverse events occurring over the course of the 4 week study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

4 weeks

Results posted on

2019-06-13

Participant Flow

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.

All patients screened to participate in study were consented onto the study as planned.

Participant milestones

Participant milestones
Measure	Zoledronic Acid, Pravastatin, and Lonafarnib 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 Study STARTED	5
Overall Study Received Treatment	4
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zoledronic Acid, Pravastatin, and Lonafarnib n=5 Participants 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.
Age, Categorical <=18 years	5 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Results are reported for the 5 patients who completed the 4 weeks of therapy.

Feasibility was assessed by determining the number of participants with adverse events occurring over the course of the 4 week study.

Outcome measures

Outcome measures
Measure	Zoledronic Acid, Pravastatin, and Lonafarnib n=5 Participants 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.
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

SECONDARY outcome

Timeframe: 4 weeks

Number of participants with acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib

Outcome measures

Outcome measures
Measure	Zoledronic Acid, Pravastatin, and Lonafarnib n=5 Participants 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.
To Describe Any Acute and Chronic Toxicities Associated With Treating Progeria Patients With the Combination of Zoledronic Acid, Pravastatin and Lonafarnib	0 Participants

SECONDARY outcome

Timeframe: 4 weeks

The number of participants with abnormal CBC w/diff panel, LFTs, renal functions and lipid panels.

Outcome measures

Outcome measures
Measure	Zoledronic Acid, Pravastatin, and Lonafarnib n=5 Participants 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.
To Investigate Which Clinical and Laboratory Studies Are Needed to Monitor or Alter Therapy to Prevent Unacceptable Toxicity	0 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 weeks

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 weeks

The number of participants from whom baseline clinical and Laboratory data was obtained.

Outcome measures

Outcome measures
Measure	Zoledronic Acid, Pravastatin, and Lonafarnib n=5 Participants 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.
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 Participants

Adverse Events

Zoledronic Acid, Pravastatin, and Lonafarnib

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Mark Kieran

Dana-Farber Cancer Institute

Phone: 617-632-4907

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place