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Protocol Details

A Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Assess The Efficacy, Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Venglustat in Late-Onset GM2 Gangliosidosis (Tay-Sachs Disease And Sandhoff Disease) Together With a Separate Basket for Juvenile/Adolescent Late-Onset GM2 Gangliosidosis and Ultra-Rare Diseases Within the Same and Similar Glucosylceramide-Based Sphingolipid Pathway

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 2 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women



Recruitment Keyword(s)



late-onset GM2;

Investigational Drug(s)


Investigational Device(s)



Drug: Venglustat
Drug: Placebo

Supporting Site

National Human Genome Research Institute


Tay-Sachs disease and Sandhoff disease are rare genetic disorders. They are known as GM2 gangliosidosis. There is no specific therapy for these diseases. Researchers want to see if a new drug can help people with these and allied diseases.


To assess the possible risks, effectiveness, and effects of venglustat in people with gangliosidosis and allied diseases.


Adults ages 18years and over with late-onset Tay-Sachs and Sandhoff disease in the main portion of the trial and subjects 2 years and older with GM1 gangliosidosis, GM2 gangliosidosis, sialidosis and galactosialidosis in the smaller basket portion of the trial.


Participants will be screened with the following:

Medical history

Physical exam with vital signs

Blood and urine tests

Electrocardiogram. It records the electrical activity of the heart. Sticky pads will be attached to their arms, legs, and chest.

Neurological exam

Eye exam. Their pupils will be dilated. Photographs may be taken.

Tests of their speech, mobility, and extremity function

Tests of accuracy, balance, and stability

Questionnaires about their quality of life and depression symptoms

Screening tests will be repeated during the study.

Genetic tests will be done on some blood samples.

Participants will have two lumbar punctures (spinal taps). A needle will be inserted between two lumbar vertebrae into the sack that surrounds the spinal cord. Fluid will be collected.

Participants will take a venglustat or placebo tablet by mouth once a day for 104 weeks.

Participants will be evaluated at the NIH after starting the medication at week 12, week 26, week 39, week 52, week 65, week 78, week 104, and week 110.

Participants will keep a diary to record any safety issues and other details. They will be contacted by phone every 2 months.

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Participants are eligible to be included in the study only if all of the following criteria apply:


1. Participant must be at least 18 years of age at the time of signing the informed consent for the primary population and adult secondary population. Participant must be greater than or equal to 2 to <18 years of age at the time of signing the informed consents (participant and parent/guardian) for the juvenile and adolescent secondary population.

Type of participant and disease characteristics:

2. The participant has a clinical diagnosis of late-onset GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease) and documented respective enzyme deficiency (for the primary population only). The documented enzyme deficiency should support a genetically confirmed diagnosis of GM2-gangliosidosis caused by beta-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes.

Note: The study may also enroll participants with a clinical diagnosis of juvenile/adolescent late-onset GM2 gangliosidosis, GM1 gangliosidosis, Saposin C deficiency, Sialidosis type 1, or juvenile/adult galactosialidosis if any of the sites have such participants meeting the other inclusion and none of the exclusion criteria (secondary population). The secondary population is composed of participants with ultra-rare conditions within the same biochemical pathway as the primary population.

3. For primary population, the participant has the ability to perform the 9-HPT at the screening visit in less than or equal to 240 seconds for the 2 consecutive trials of the dominant hands and the 2 consecutive trials of the nondominant hand.

4. If the participant has a history of seizures, they are well controlled under appropriate medication not identified as a strong or moderate inducer or inhibitor of CYP3A4.

5. The participant is cooperative, able to ingest oral medication, willing to travel to a study site (if applicable), and able to comply with all aspects of the study, including all assessments, according to the Investigator s judgment.


6. For the juvenile and adolescent secondary population, participant must have body weight greater than or equal to 10 kg at the time of signing the informed consent.


7. Male or Female

Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

a) Sexually active male participants

A male participant must agree to use contraception for the duration of the study and 90 days following their last dose of study intervention.

b) Female participants

A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

- Not a woman of childbearing potential (WOCBP)


- A WOCBP who agrees to follow the contraceptive guidance for the duration of the study and for at least 6 weeks after the last dose of study intervention.

Informed Consent:

8. The participant or if appropriate parent(s) or legal guardian(s) must provide written informed assent/consent prior to any study-related procedures being performed.


Participants are excluded from the study if any of the following criteria apply:

Medical conditions:

1. Participant has clinical features of Tay-Sachs or Sandhoff disease, but a completely negative result on a genetic test for GM2 gangliosidosis caused by beta-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes and/or is without

clinical features.

2. For primary population and participants with juvenile/adolescent late onset GM2 gangliosidosis and GM1 gangliosidosis, the participant cannot understand and perform all age-appropriate study assessments with the exception of 25FWT.

3. Any clinically relevant medical disorders other than late-onset GM2 gangliosidosis (primary population) or the diseases specified for the secondary population, clinically relevant findings in the physical examination, medical history, or laboratory assessments which would compromise the safety of the participant. This includes condition(s) that precludes the safe performance of routine lumbar puncture (eg, prohibitive lumbar spinal disease), as well as cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (eg, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses.

4. The participant has a documented diagnosis of any of the following infections: hepatitis B, hepatitis C, human immunodeficiency virus 1 or 2.

5. A history of drug and/or alcohol abuse within the past year prior to the first screening visit.

6. The participant is scheduled for in-patient hospitalization including elective surgery during the study.

7. The participant has, according to World Health Organization (WHO) grading, a cortical cataract >= one-quarter of the lens circumference (Grade cortical cataract-2) or a posterior subcapsular cataract >=2 mm (Grade posterior subcapsular cataract-2). Participants with nuclear cataracts will not be excluded.

Prior/concomitant therapy:

8. The participant requires use of invasive ventilatory support.

9. The participant is receiving current treatment with anticoagulants (eg, coumadin, heparin) that might preclude safe completion of the LP.

10. The participant has received SRT within 3 months prior to study enrollment.

11. The participant has received strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half-lives, whichever is longer, prior to study enrolment.

12. The participant is currently receiving potentially cataractogenic medications or any medication that may worsen the vision of participant with cataract (eg, alpha-adrenergic glaucoma medications) according to the prescribing information.

Prior/concurrent clinical study experience:

13. Currently participating in another investigational interventional study.

14. Use of IMP, within 3 months or 5 half-lives, whichever is longer, before study enrollment.

Note: For participants using N-acetyl-leucine as IMP, within 5 half-lives before study enrollment.

Diagnostic assessments:

15. Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total bilirubin >2 (SqrRoot) the upper limit of normal (ULN) at the time of screening unless the participant has the diagnosis of Gilbert syndrome and maintains a level of total bilirubin

<5 mg/dl and direct bilirubin <1 mg/dl (20%) of total bilirubin level.

16. Renal insufficiency as defined by estimated glomerular filtration rate <30 mL/min/1.73 m2 at the screening visit.

Other Exclusions:

17. Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.

18. Any country-related specific regulation that would prevent the participant from entering the study (country-specific requirements).

19. Participant not suitable for participation, whatever the reason, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

20. Participants are dependent on the Sponsor or Investigator

21. Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.

22. Any specific situation during study implementation/course that may raise ethics considerations.

23. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy, that contraindicates participation in the study.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Cynthia J. Tifft, M.D.
National Human Genome Research Institute (NHGRI)
NIHBC 10 - CRC BG RM 3-2551
(301) 451-8485

Andrea L. Ashton
National Human Genome Research Institute (NHGRI)
BG 10-CRC RM 3-2551
(301) 496-7125

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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