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Phase II Trial of Lonafarnib (a Farnesyltransferase Inhibitor) for Progeria

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ClinicalTrials.gov Identifier: NCT00425607
Recruitment Status : Completed
First Posted : January 23, 2007
Results First Posted : May 24, 2017
Last Update Posted : April 10, 2018
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Monica E. Kleinman, Boston Children’s Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Progeria
Hutchinson-Gilford Syndrome
Intervention Drug: Lonafarnib
Enrollment 29
Recruitment Details 26 patients with classic HGPS from 16 countries were enrolled from May through October 2007 at Boston Children's Hospital. 2 additional patients had nonclassic mutations and are not included in the analyses.
Pre-assignment Details One additional patient signed consent but withdrew from the protocol before receiving therapy.
Arm/Group Title Lonafarnib
Hide Arm/Group Description Lonafarnib (Merck & Co., Inc.) dosing was initiated at 115 mg/m2 and was increased to 150 mg/m2 after an adjustment period of at least 4 mo. Dosage was reduced back to 115 mg/m2 for patients experiencing drug-related grade 3 or 4 toxicity and also not responding to supportive care. Once dosage was reduced, patients were permitted to increase the dose of lonafarnib. Patients received oral lonafarnib either by capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus (Paddock Laboratories, Inc.) every 12 ± 2 h for a period of 24–29 mo.
Period Title: Overall Study
Started 29
Received Treatment 28
Completed 27
Not Completed 2
Reason Not Completed
Death             1
Withdrawal by Subject             1
Arm/Group Title Lonafarnib
Hide Arm/Group Description Lonafarnib (Merck & Co., Inc.) dosing was initiated at 115 mg/m2 and was increased to 150 mg/m2 after an adjustment period of at least 4 mo. Dosage was reduced back to 115 mg/m2 fo patients experiencing drug-related grade 3 or 4 toxicity and also not responding to supportive care. Once dosage was reduced, patients were permitted to increase the dose of lonafarnib. Patients received oral lonafarnib either by capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus (Paddock Laboratories, Inc.) every 12 ± 2 h for a period of 24–29 mo.
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
The analysis population represents the 25 patients with classic HGPS who received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. The analysis population does not include 1 patient (with prior history of strokes) who died of a stroke after 5 mo on study, or 2 additional patients who had nonclassic mutations.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
7.0  (3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
14
  56.0%
Male
11
  44.0%
1.Primary Outcome
Title Proportion of Participants With Successful Rate of Weight Gain
Hide Description

Activity was assessed by determining the change in rate of weight gain over two years from baseline (determined pre-therapy for each patient).

Primary outcome success was predefined as a 50% increase over pre-therapy in estimated annual rate of weight gain, or change from pre-therapy weight loss to statistically significant on-study weight gain.

Time Frame Assessed at weeks 16, 32, 52, 68, 84 and 104
Hide Outcome Measure Data
Hide Analysis Population Description
Results are reported for the 25 patients with classic HGPS who completed at least 2y of therapy. One additional patient with a prior history of strokes died of a stroke after 5 mo on study and is not included in the analysis. Two additional patients had nonclassic mutations and are not included in this analysis.
Arm/Group Title Lonafarnib
Hide Arm/Group Description:
Lonafarnib (Merck & Co., Inc.) dosing was initiated at 115 mg/m2 and was increased to 150 mg/m2 after an adjustment period of at least 4 mo. Dosage was reduced back to 115 mg/m2 for patients experiencing drug-related grade 3 or 4 toxicity and also not responding to supportive care. Once dosage was reduced, patients were permitted to increase the dose of lonafarnib. Patients received oral lonafarnib either by capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus (Paddock Laboratories, Inc.) every 12 ± 2 h for a period of 24–29 mo.
Overall Number of Participants Analyzed 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.36
(0.18 to 0.58)
Time Frame Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lonafarnib
Hide Arm/Group Description Lonafarnib (Merck & Co., Inc.) dosing was initiated at 115 mg/m2 and was increased to 150 mg/m2 after an adjustment period of at least 4 mo. Dosage was reduced back to 115 mg/m2 fo patients experiencing drug-related grade 3 or 4 toxicity and also not responding to supportive care. Once dosage was reduced, patients were permitted to increase the dose of lonafarnib. Patients received oral lonafarnib either by capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus (Paddock Laboratories, Inc.) every 12 ± 2 h for a period of 24–29 mo. Patients were monitored for liver, kidney, and hematological toxicity each month for the first 3 mo by their local physicians and every 4 mo in Boston for the duration of the study. Adverse events were monitored and recorded throughout the study.
All-Cause Mortality
Lonafarnib
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lonafarnib
Affected / at Risk (%) # Events
Total   10/28 (35.71%)    
Blood and lymphatic system disorders   
Hypokalemia  1  1/28 (3.57%)  1
Gastrointestinal disorders   
Vomiting  1  2/28 (7.14%)  2
Infections and infestations   
Bacterial infection  1 [1]  1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders   
Extremity-lower (gait/walking)  1  1/28 (3.57%)  1
Nervous system disorders   
Stroke  1  3/28 (10.71%)  3
Subdural hematoma  1  1/28 (3.57%)  1
Neuropathy: Sensory  1 [2]  1/28 (3.57%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
H. Pylori infection
[2]
Paresthesia
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Lonafarnib
Affected / at Risk (%) # Events
Total   0/28 (0.00%)    
This was an open label clinical trial on a very rare disease population. Patient numbers are small, though 26 participants represents a 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
Name/Title: Dr. Mark Kieran
Organization: Dana-Farber Cancer Institute
Phone: 617-632-4907
Publications of Results:
Responsible Party: Monica E. Kleinman, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT00425607     History of Changes
Obsolete Identifiers: NCT00426088
Other Study ID Numbers: 07-01-007
P05009 ( Other Identifier: Schering-Plough )
First Submitted: January 22, 2007
First Posted: January 23, 2007
Results First Submitted: September 25, 2015
Results First Posted: May 24, 2017
Last Update Posted: April 10, 2018