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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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ClinicalTrials.gov |
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Last refreshed on:
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19 February 2015 |
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Main ID: |
NCT00679744 |
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Date of registration:
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15/05/2008 |
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Prospective Registration:
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No |
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Primary sponsor: |
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Public title:
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A Phase I Study of Pyrimethamine in Patients With GM2 Gangliosidosis
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Scientific title:
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A Dose-Escalated, Double-Blind, Placebo-Controlled, Randomized Phase I Clinical Trial of Pyrimethamine in Patients Affected With Chronic GM2 Gangliosidosis (Tay-Sachs or Sandhoff Variants) |
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Date of first enrolment:
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May 2008 |
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Target sample size:
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0 |
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Recruitment status: |
Withdrawn |
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URL:
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http://clinicaltrials.gov/show/NCT00679744 |
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Study type:
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Interventional |
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Study design:
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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Phase:
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Phase 1
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Countries of recruitment
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Canada
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United States
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Contacts
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Name:
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Bijan Almassian, Ph.D. |
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Address:
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Telephone:
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Email:
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Affiliation:
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Exsar Corporation |
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Key inclusion & exclusion criteria
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Inclusion Criteria:
- Biochemically and genetically confirmed diagnosis of GM2 Gangliosidosis caused by
ß-hexosaminidase deficiency resulting from mutations in the HEX-A or HEX-B genes,
which has been shown to respond to Pyrimethamine treatment in previous cell culture
experiments (Maegawa et al. 2006).
- Must be 18 years of age or older to participate in the study.
- Able to understand and cooperate with the requirements of the study protocol.
- Mentally competent, have ability to understand and willingness to sign the informed
consent form.
- Able to travel to the participating study site.
- Women of child-bearing potential must use accepted contraceptive methods, and must
have a negative serum or urine pregnancy test within 2 days 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 be within acceptable range.
- Body weight >40 kg (88 pounds).
Exclusion Criteria:
- Serious medical illness, significant cardiac disease that would increase patients'
risk for toxicity.
- Any hematologic or related abnormality, especially megaloblastic anemia, leukopenia,
thrombocytopenia, pancytopenia, atrophic glossitis, hematuria, and disorders of
cardiac rhythm, pulmonary eosinophilia, etc.
- Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g.,
active peptic ulcer disease).
- Possible folate deficiency, such as individuals with malabsorption syndrome,
alcoholism, or pregnancy, 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 (because Pyrimethamine is a "Pregnancy Category C" product).
- Lactating females because of the potential for serious adverse reactions in nursing
infants.
- 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
or to the inactive ingredients (corn and potato starch, lactose, and magnesium
stearate).
- Evidence of systemic infection, or anyone who in the opinion of the investigator
would not be suitable for the study.
- Test positive for HIV.
- Test positive for hepatitis B or hepatitis C.
- Patients with a history of convulsive disorders, since these patients are very
susceptible to the nervous system toxicity of Pyrimethamine.
- Patients receiving any other investigational treatment for any indication within the
past 4 weeks prior to initiation of Pyrimethamine treatment.
- A history of cancer of any type, since Pyrimethamine may be carcinogenic.
- Patients who have received immunotherapy of any type within the past 4 weeks prior to
initiation of Pyrimethamine treatment.
- Patients who are receiving antifolic drugs and drugs associated with
myelosuppression, or patients who are receiving drugs, when used in combination with
Pyrimethamine, have been reported to induce some degree of hepatotoxicity:
- Any condition or abnormality which may, in the opinion of the investigator,
compromise the safety of patients.
Age minimum:
18 Years
Age maximum:
N/A
Gender:
Both
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Health Condition(s) or Problem(s) studied
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Sandhoff Disease Ganglioside
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Tay-Sachs Disease Ganglioside
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G(M2) Ganglioside
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Intervention(s)
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Drug: Pyrimethamine
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Primary Outcome(s)
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The primary outcome measure is safety and tolerability, based on conventional laboratory and clinical assessments.
[Time Frame: The primary outcome measure, which is safety and tolerability, will be assessed weekly during the 8-week treatment period and biweekly during the 4-week post-treatment period.]
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Secondary Outcome(s)
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The secondary outcome measure is to assess changes in ß-hexosaminidase A and B activities in plasma and peripheral blood leukocytes.
[Time Frame: The secondary outcome measure will be assessed weekly during the 4-week treatment period and at the end of the 4-week post-treatment period.]
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Secondary ID(s)
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CL-Pyrimethamine-001
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3448
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FDA OPD Grant: FD-R-03448-01
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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