To demonstrate that N-Acetyl-L-Leucine is effective in improving symptoms, functioning and quality of life in patients with GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease).
- Conditions
- To demonstrate that N-Acetyl-L-Leucine is effective in improvingsymptoms, functioning, and quality of life in patients GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease).MedDRA version: 20.0Level: PTClassification code 10043147Term: Tay-Sachs diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 21.1Level: PTClassification code 10081314Term: Sandhoff diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-004406-25-GB
- Lead Sponsor
- IntraBio Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 39
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/impartial witness
2. Male or female aged =6 years in Europe OR =18 years in the United States with a
confirmed diagnosis of GM2 Gangliosidosis at the time of signing informed
consent. Confirmed diagnosis, i.e., clinical features and positive genetic test GM2-
gangliosidosis caused by ß-hexosaminidase deficiency resulting from mutations in the
HEXA or HEXB genes
3. Females of childbearing potential, defined as a premenopausal female capable of
becoming pregnant, will be included if they are either sexually inactive (sexually
abstinent4 for 14 days prior to the first dose and confirm to continue 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:
a) intrauterine device (IUD);
b) surgical sterilization of the partner (vasectomy for 6 months minimum);
c) combined (estrogen or progestogen containing) hormonal contraception associated
with the inhibition of ovulation (either oral, intravaginal, or transdermal);
d) progestogen only hormonal contraception associated with the inhibition of
ovulation (either oral, injectable, or implantable);
e) intrauterine hormone releasing system (IUS);
f) 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:
a) hysteroscopic sterilization;
b) bilateral tubal ligation or bilateral salpingectomy;
c) hysterectomy;
d) 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, patient agrees not to donate sperm from the first dose until 90 days after theirlast dose.
7. Patients must fall within:
a) A SARA score of 5 = X = 33 points (out of 40)
AND
b) Either:
i. Within the 2-7 range (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. Nonprohibited medications/therapies (e.g. concomitant speech therapy, and physiotherapy) are permitted provided:
a) The Investigator does not believe the medication/therapy will interfere with the
study protocol/results
b) Patients have been on a stable dose
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 GM2 Gangliosidosis, but a completely negative result on a previous genetic test for GM2 Gangliosidosis
3. Patients who have any of the following:
a) Chronic diarrhea;
b) Unexplained visual loss;
c) Malignancies;
d) Insulin-dependent diabetes mellitus.
e) Known history of hypersensitivity to the Acetyl-Leucine (DL-, L-, D-) or
derivatives.
f) 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:
a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x
upper limit of normal (ULN);
b. 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 diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affects patient’s mobility and, at the investigator’s discretion, interferes with their ability to perform study assessments.
11. Patients unwilling and/or not able to undergo a 42 day washout period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6.
a) Aminopyridines (including sustained-release form);
b) N-Acetyl-DL-Leucine (e.g. Tanganil®);
c) N-Acetyl-L-Leucine (prohibited if not provided as IMP);
d) Riluzole;e) Gabapentin;
f) Varenicline;
g) Chlorzoxazone;
h) Sulfasalazine;
i) Rosuvastatin.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method