N-Acetyl-L-Leucine for GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease)

• Register: ClinicalTrials.gov
• Last refreshed on: 13 March 2023
• Main ID: NCT03759665
• Date of registration: 27/11/2018
• Prospective Registration: Yes
• Primary sponsor: IntraBio Inc
• Public title: N-Acetyl-L-Leucine for GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease)
• Scientific title: Effects of N-Acetyl-L-Leucine on GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease): A Multinational, Multicenter, Open-label, Rater-blinded Phase II Study
• Date of first enrolment: June 7, 2019
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03759665
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Germany, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

Parent Study Inclusion Criteria

Individuals who meet all of the following criteria are eligible to participate in the
study:

1. Written informed consent signed by the patient and/or their legal representative/
parent

2. Male or female aged =6 years in Europe OR =18 years in the United States with a
confirmed diagnosis of GM2 Gangliosidosis ( i.e., clinical features and positive
genetic test GM2-gangliosidosis caused by ß-hexosaminidase deficiency resulting from
mutations in the HEXA or HEXB genes) at the time of signing informed consent.

3. Females of childbearing potential, defined as a premenopausal female capable of
becoming pregnant, will be included if they are either sexually inactive (sexually
abstinent for 14 days prior to the first dose continuing through 28 days after the
last dose) or using one of the following highly effective contraceptives (i.e. results
in <1% failure rate when used consistently and correctly) 14 days prior to the first
dose continuing through 28 days after the last dose:

1. intrauterine device (IUD);

2. surgical sterilization of the partner (vasectomy for 6 months minimum);

3. combined (estrogen or progestogen containing) hormonal contraception associated
with the inhibition of ovulation (either oral, intravaginal, or transdermal);

4. progestogen-only hormonal contraception associated with the inhibition of
ovulation (either oral, injectable, or implantable);

5. intrauterine hormone-releasing system (IUS);

6. bilateral tubal occlusion.

4. Females of non-childbearing potential must have undergone one of the following
sterilization procedures at least 6 months prior to the first dose:

1. hysteroscopic sterilization;

2. bilateral tubal ligation or bilateral salpingectomy;

3. hysterectomy;

4. bilateral oophorectomy;

OR

be postmenopausal with amenorrhea for at least 1 year prior to the first dose and
follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.
FSH analysis for postmenopausal women will be done at screening. FSH levels should be
in the postmenopausal range as determined by the central laboratory.

5. Non-vasectomized male patient agrees to use a condom with spermicide or abstain from
sexual intercourse during the study until 90 days beyond the last dose of study
medication and the female partner agrees to comply with inclusion criteria 3 or 4. For
a vasectomized male who has had his vasectomy 6 months or more prior to study start,
it is required that they use a condom during sexual intercourse. A male who has been
vasectomized less than 6 months prior to study start must follow the same restrictions
as a non-vasectomized male.

6. If male, the patient agrees not to donate sperm from the first dose until 90 days
after dosing.

7. Patients must fall within:

a) A SARA score of 5 = X = 33 points (out of 40) AND i. Within the 2-7 range (out of
0-8 range) of the Gait subtest of the SARA scale OR ii. Be able to perform the 9 Hole
Peg Test with Dominant Hand (9HPT-D) (SCAFI subtest) in 20 = X =150 seconds.

8. Weight =15 kg at screening.

9. Patients are willing to disclose their existing medications/therapies for (the
symptoms) of GM2 Gangliosidosis, including those on the prohibited medication list.
Non-prohibited medications/therapies (e.g. concomitant speech therapy, and
physiotherapy) are permitted provided:

1. The Investigator does not believe the medication/therapy will interfere with the
study protocol/results

2. Patients have been on a stable dose/duration and type of therapy for at least 6
weeks before Visit 1 (Baseline 1)

3. Patients are willing to maintain a stable dose/do not change their therapy
throughout the duration of the study.

10. An understanding of the implications of study participation, provided in the written
patient information and informed consent by patients or their legal
representative/parent, and demonstrates a willingness to comply with instructions and
attend required study visits (for children this criterion will also be assessed in
parents or appointed guardians).

Parent Study Exclusion Criteria

Individuals who meet any of the following criteria are not eligible to participate in the
study:

1. Asymptomatic patients

2. Patient has clinical features of Tay-Sachs or Sandhoff disease, but a completely
negative result on a previous genetic test for GM2 Gangliosidosis caused by
ß-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes

3. Patients who have any of the following:

1. Chronic diarrhea;

2. Unexplained visual loss;

3. Malignancies;

4. Insulin-dependent diabetes mellitus.

5. Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or
derivatives.

6. History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose,
sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan,
dimethicone, methylparaben, and potassium sorbate).

4. Simultaneous participation in another clinical study or participation in any clinical
study involving administration of an investigational medicinal product (IMP; 'study
drug') within 6 weeks prior to Visit 1.

5. Patients with a physical or psychiatric condition which, at the investigator's
discretion, may put the patient at risk, may confound the study results, or may
interfere with the patient's participation in the clinical study.

6. Known clinically-significant (at the discretion of the investigator) laboratories in
hematology, coagulation, clinical chemistry, or urinalysis, including, but not limited
to:

1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper
limit of normal (ULN);

2. Total bilirubin >1.5x ULN, unless Gilbert's syndrome is present in which case
total bilirubin >2x ULN.

7. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.

8. Current or planned pregnancy or women who are breastfeeding.

9. Patients with severe vision or hearing impairment (that is not corrected by glasses or
hearing aids) that, at the investigator's discretion, interferes with their ability to
perform study assessments.

10. Patients who have been diagnos


Age minimum: 6 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Tay-Sachs Disease

GM2 Gangliosidosis

Sandhoff Disease

Intervention(s)

Drug: IB1001

Primary Outcome(s)

Clinical Impression of Change in Severity (CI-CS) [Time Frame: CI-CS comparing Baseline (Day 1) with IB1001 verses the end of 6-weeks treatment with IB1001 (Approximately Day 42) MINUS the CI-CS comparing the end of 6-weeks treatment with IB1001 (Approximately Day 42) verses the end of 6-weeks post-treatment washout]

Secondary Outcome(s)

Scale for Assessment and Rating of Ataxia (SARA) score [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42; Extension Phase Day 365); End of treatment with IB1001 to the end of post treatment washout (Parent Study & Extension Phase - 42 days following end of treatment)]

Parent/Caregiver's Clinical Global Impressions (CGI) [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42; Extension Phase Day 365); End of treatment with IB1001 to the end of post treatment washout (Parent Study & Extension Phase - 42 days following end of treatment)]

Modified Disability Rating Scale (mDRS) [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42); End of treatment with IB1001 to the end of post treatment washout (Parent Study 42 days following end of treatment)]

Investigator's Clinical Global Impressions (CGI) [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42; Extension Phase Day 365); End of treatment with IB1001 to the end of post treatment washout (Parent Study & Extension Phase - 42 days following end of treatment)]

EuroQuol - 5 Dimension (EQ-5D) Quality of Life Scale [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42; Extension Phase Day 365); End of treatment with IB1001 to the end of post treatment washout (Parent Study & Extension Phase - 42 days following end of treatment)]

Patient's Clinical Global Impressions (CGI) if able [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42; Extension Phase Day 365); End of treatment with IB1001 to the end of post treatment washout (Parent Study & Extension Phase - 42 days following end of treatment)]

Spinocerebellar Ataxia Functional Index (SCAFI) [Time Frame: Baseline to end of treatment with IB1001 (Parent Study Day 42; Extension Phase Day 365); End of treatment with IB1001 to the end of post treatment washout (Parent Study & Extension Phase - 42 days following end of treatment)]

Secondary ID(s)

IB1001-202

Source(s) of Monetary Support

Please refer to primary and secondary sponsors