Overview

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.