Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

• Status: Completed
• Trial end date: 2010-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The objectives of this clinical trial are to assess the safety and tolerability, as well as efficacy, of a stepwise dosing regimen of pyrimethamine, starting at 25 mg/day, given as a single dose daily for 4 weeks in patients affected with chronic Tay-Sachs or Sandhoff variants.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Hospital for Sick Children
• Treatments: Leucovorin; Pyrimethamine

Criteria

Inclusion Criteria:

• biochemically and genetically confirmed diagnosis of GM2-gangliosidosis caused by β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes;

• having HEXA or HEXB mutations shown to be responsive to pyrimethamine in vitro;

• over 17 years of age at the time of study initiation;

• able to understand and cooperate with the requirements of the study protocol;

• mentally competent, have the ability to understand and willingness to sign the informed consent form;

• able to travel to one of the three participating study sites;

• women of child-bearing potential must use accepted contraceptive methods and must have a negative serum or urine pregnancy test within one week prior to treatment initiation;

• fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists;

• laboratory values ≤2 weeks prior to randomization must show adequate hematologic, hepatic, renal, and coagulation function; and body weight >40 kg.

Exclusion Criteria:

• serious medical illness, significant cardiac disease or severe debilitating pulmonary disease;

• any hematologic abnormality, especially megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia;

• any active uncontrolled bleeding or any bleeding diathesis (e.g., active peptic ulcer disease);

• possible folate deficiency, and those receiving therapy (such as phenytoin) affecting folate levels;

• any complex disease that may confound treatment assessment;

• pregnant women or women of child-bearing potential not using reliable means of contraception;

• lactating females;

• fertile men unwilling to practice contraceptive methods during the study period;

• unwilling or unable to follow protocol requirements;

• known hypersensitivity reactions, intolerance or adverse reactions to pyrimethamine;

• evidence of active infection, or serious infection within the past month;

• HIV infection;

• a history of cancer of any type;

• receiving any other standard or investigational treatment for any indication within the past 4 weeks prior to initiation of pyrimethamine treatment;

• receiving immunotherapy of any type within the past 4 weeks prior to initiation of pyrimethamine treatment; or any condition or abnormality, which may, in the opinion of the investigator, compromise the safety of patients.