Progeria Clinical Trial
Official title:
An Open Label Dose Adjusted Phase II Trial of the Oral Farnesyltransferase Inhibitor (FTI) Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathies
Verified date | June 2019 |
Source | Boston Children’s Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is an open label dose adjusted phase II trial of the oral farnesyltransferase inhibitor (FTI) lonafarnib (SCH66336) for patients with HGPS and progeroid laminopathies.
Status | Completed |
Enrollment | 29 |
Est. completion date | October 2009 |
Est. primary completion date | October 2009 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Year and older |
Eligibility |
Inclusion Criteria: - All patients must have confirmatory mutational analysis showing G608G mutation in the lamin A gene. - Patients with progeroid laminopathies, showing clinical signs of Progeria but with other confirmed mutations in LMNA will be eligible for therapy. This population will be analyzed separately from those with the classical mutations. - Patients must be willing and able to come to Boston for appropriate studies and examinations approximately once every 4 months. - Patients must have a minimum of one year of weight data available, with five data points or more, each separated by one month or more over a one year period and approval by the study team. - APC (ANC + bands + monocytes = APC) > 1,000/ml, Platelets > 75,000/ml (transfusion independent); Hemoglobin >9g/dl. - creatinine less than or equal to 1.5 times normal for age or GFR > 70 ml/min/1.73m2. - bilirubin less than or equal to 1.5 x upper limit of normal for age; SGPT (ALT) < and SGOT (AST) < 5 x normal range for age. - PT/PTT < 120% upper limit of normal OR PI approval. - No overt renal, hepatic, pulmonary disease or immune dysfunction. - Patients taking growth hormone when entering the study must have pretreatment weight measures while on growth hormone which are specified above. In addition, patients must remain on growth hormone treatment for the duration of the present clinical trial. Patients entering the trial not on growth hormone must remain off of growth hormone for the duration of their participation. - Signed informed consent according to institutional guidelines must be obtained and patient must begin therapy within twenty eight (28) days. Exclusion Criteria: - Patient must not be receiving any other experimental drug therapy. - Patients must not be taking medications that significantly affect the metabolism of lonafarnib. - Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated. - Patients must not be pregnant or 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. |
Country | Name | City | State |
---|---|---|---|
United States | Children's Hospital Boston | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Monica E. Kleinman | Schering-Plough |
United States,
Cleveland RH, Gordon LB, Kleinman ME, Miller DT, Gordon CM, Snyder BD, Nazarian A, Giobbie-Hurder A, Neuberg D, Kieran MW. A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome. Pediatr Radiol. 2012 Sep;42(9):1089-98. — View Citation
Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland R, Snyder BD, Fligor B, Bishop WR, Statkevich P, Regen A, Sonis A, Riley S, Ploski C, Correia A, Quinn N, Ullrich NJ, Nazarian A, Liang MG, H — View Citation
Gordon LB, Massaro J, D'Agostino RB Sr, Campbell SE, Brazier J, Brown WT, Kleinman ME, Kieran MW; Progeria Clinical Trials Collaborative. Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation. 2014 Jul 1;130(1 — View Citation
Silvera VM, Gordon LB, Orbach DB, Campbell SE, Machan JT, Ullrich NJ. Imaging characteristics of cerebrovascular arteriopathy and stroke in Hutchinson-Gilford progeria syndrome. AJNR Am J Neuroradiol. 2013 May;34(5):1091-7. doi: 10.3174/ajnr.A3341. Epub 2 — View Citation
Ullrich NJ, Kieran MW, Miller DT, Gordon LB, Cho YJ, Silvera VM, Giobbie-Hurder A, Neuberg D, Kleinman ME. Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. Neurology. 2013 Jul 30;81(5):427-30. doi: 10.1212/WNL.0b013e — View Citation
Ullrich NJ, Silvera VM, Campbell SE, Gordon LB. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome. AJNR Am J Neuroradiol. 2012 Sep;33(8):1512-8. doi: 10.3174/ajnr.A3088. Epub 2012 Mar 29. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Proportion of Participants With Successful Rate of Weight Gain | 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. |
Assessed at weeks 16, 32, 52, 68, 84 and 104 |
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