Phase II Trial of Lonafarnib (a Farnesyltransferase Inhibitor) for Progeria
Condition: Progeria; Hutchinson-Gilford Syndrome
MeSH terms: Progeria; Syndrome
Intervention: Lonafarnib
Intervention description: Lonafarnib will be taken orally, twice per day, by all patients enrolled on this study. The drug is supplied to patients in capsule form, and for patients who are unable to swallow pills, the drug may be dissolved into solution. Every patient will start lonafarnib therapy at a dose of 115mg/kg. The study allows for patients to receive a dose escalation (up to 150mg/kg) if the drug is being well-tolerated. Every patient enrolled on this study will undergo two years of lonafarnib therapy.
Intervention MeSH terms: Lonafarnib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: Open Label
Enrollment: 29.0
Sex: All
Minimum age: 1 Year
Healthy volunteers: No
Keywords: Hutchinson-Gilford Progeria Syndrome; HGPS; Progeria; FTI; Farnesyltransferase Inhibitor; Lonafarnib

Summary:

      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.
    

Eligibility criteria:

        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.