Study to Determine Optimal Dose and Evaluate Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients with Hutchinson-Gilford Progeria Syndrome (HGPS)

Eligibility Criteria

• 1. Subjects ≥ 1 year of age and weight ≥ 17.6 lb (8 kg).
• 2. Subject must have confirmatory mutational analysis showing the classic Hutchinson-Gilford Progeria Syndrome (HGPS) mutation (c. 1824 C\>T), nonclassic HGPS, Zmpset24 gene mutation, or other LMNA mutation (all subjects will have documentation of genetic testing prior to enrollment). \*Only subjects with progerin producing mutations will be eligible for randomization. Other PL are eligible to enroll as naïve subjects (see note for criterion #5).
• 3. Subject must display clinical signs of Progeria as per the clinical trial team.
• 4. Subject must be willing and able to come to Boston for appropriate assessments and examinations.
• 5. Subject must be taking lonafarnib for at least 4 months prior to enrollment and have no history of grade 3 or 4 side effects that can be probably or possibly attributed to lonafarnib for at least 2 months prior to enrollment.
• 6. Subjects must have had no recent fractures or major surgery (within four weeks).
• 7. Subject must have adequate organ and marrow function as defined by the following parameters:
• 1. Blood: absolute phagocyte count (APC) (absolute neutrophil count \[ANC\] + bands + monocytes) \>1,000/μL, platelets \>75,000/μL (transfusion independent); hemoglobin \>9 g/dL.
• 2. Renal: creatinine ≤ 1.5 times normal for age or Glomerular Filtration Rate (GFR) \>70 mL/min/1.73m2.
• 3. Hepatic: bilirubin ≤1.5x upper limit of normal for age; Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Transaminase, \[ALT\]) \< and Serum Glutamic-Oxaloacetic Transaminase (SGOT) (Aspartate Aminotransferase, \[AST\]) ≤ 2.5x normal range for age.
• 8. The subject is willing to provide written informed assent form, when possible, to participate in the study after reading the informed assent form and the information provided and has had the opportunity to discuss the study with the investigator or designee. Additionally, the subject's legally authorized guardian (LAR) is willing to provide written informed consent.
• 9. The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
• 10. The subject (or LAR) is able to understand the nature of the study and any potential hazards associated with participating in it.
• 11. Negative pregnancy test for female subjects of childbearing potential and those who have not been surgically sterilized or who do not have verbal or laboratory confirmation of two years postmenopausal status. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Women of childbearing potential should use an acceptable method of birth control and agree to continue to use this method for the duration of the study and for 90 days after taking the last dose of Progerinin.
• 1. Other than the drugs used in this protocol, other drugs targeted to treat Progeria are excluded. Drugs to treat symptoms of Progeria are permitted.
• 2. Subjects are taking medications that significantly affect the metabolism of Progerinin.
• 3. Subjects with an active bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin).
• 4. Subjects who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• 1. known severely impaired lung function
• 2. active (acute or chronic) or uncontrolled severe infections.
• 3. liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
• 4. history of hepatitis B or hepatitis C documented by history and confirmed by serology if positive for history.
• 5. Other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
• 6. A known history of Human Immunodeficiency Virus (HIV) seropositivity or known immunodeficiency.
• 7. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Progerinin (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed.
• 8. Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated.
• 9. Subjects who have used marijuana or other (Tetrahydrocannabinol) THC containing products either recreationally or for medical purposes within three months prior to entering the study.