Trial Outcomes & Findings for Phase II Trial of Lonafarnib (a Farnesyltransferase Inhibitor) for Progeria (NCT NCT00425607)
NCT ID: NCT00425607
Last Updated: 2019-06-25
Results Overview
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.
COMPLETED
PHASE2
29 participants
Assessed at weeks 16, 32, 52, 68, 84 and 104
2019-06-25
Participant Flow
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.
One additional patient signed consent but withdrew from the protocol before receiving therapy.
Participant milestones
| Measure |
Lonafarnib
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.
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|---|---|
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Overall Study
STARTED
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29
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Overall Study
Received Treatment
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28
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Overall Study
COMPLETED
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27
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Overall Study
NOT COMPLETED
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2
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Reasons for withdrawal
| Measure |
Lonafarnib
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.
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|---|---|
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Overall Study
Death
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1
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Overall Study
Withdrawal by Subject
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1
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Baseline Characteristics
Phase II Trial of Lonafarnib (a Farnesyltransferase Inhibitor) for Progeria
Baseline characteristics by cohort
| Measure |
Lonafarnib
n=25 Participants
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.
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|---|---|
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Age, Continuous
|
7.0 years
STANDARD_DEVIATION 3 • n=5 Participants
|
|
Sex: Female, Male
Female
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14 Participants
n=5 Participants
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Sex: Female, Male
Male
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11 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Assessed at weeks 16, 32, 52, 68, 84 and 104Population: 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.
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.
Outcome measures
| Measure |
Lonafarnib
n=25 Participants
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.
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|---|---|
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Proportion of Participants With Successful Rate of Weight Gain
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0.36 proportion of participants
Interval 0.18 to 0.58
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Adverse Events
Lonafarnib
Serious adverse events
| Measure |
Lonafarnib
n=28 participants at risk
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.
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|---|---|
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Gastrointestinal disorders
Vomiting
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7.1%
2/28 • Number of events 2 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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|
Nervous system disorders
Stroke
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10.7%
3/28 • Number of events 3 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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|
Infections and infestations
Bacterial infection
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3.6%
1/28 • Number of events 1 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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Nervous system disorders
Subdural hematoma
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3.6%
1/28 • Number of events 1 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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Musculoskeletal and connective tissue disorders
Extremity-lower (gait/walking)
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3.6%
1/28 • Number of events 1 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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Nervous system disorders
Neuropathy: Sensory
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3.6%
1/28 • Number of events 1 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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|
Blood and lymphatic system disorders
Hypokalemia
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3.6%
1/28 • Number of events 1 • Up to 2 years: Assessed at a minimum at weeks 16, 32, 52, 68, 84 and 104
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Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place