GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease) MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
IntraBio Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 / 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 abstinent 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 their last 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. Non-prohibited 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 be
Exclusion criteria
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: 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 6-week 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of N-Acetyl-L-Leucine based on blinded raters’ clinical impression of change in severity (CI-CS) in the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). For the Extension Phase: The primary objective is to evaluate the efficacy of N-Acetyl-L-Leucine based on blinded raters' Clinical Impression of Change in Severity (CICS) in the long-term treatment of GM2.;Secondary Objective: To assess the clinical efficacy of N-Acetyl-L-Leucine on symptoms of ataxia, functioning, and quality of life for patients with GM2 Gangliosidosis; To evaluate the safety and tolerability of N-Acetyl-L-Leucine at 4 g/day in patients with GM2 Gangliosidosis, including patients aged =18 years in the United States and patients aged =13 years in Europe, and weight-tiered doses in patients 6 to 12 years of age in Europe For the extension phase: - To assess the clinical efficacy of long-term treatment with N-Acetyl-L-Leucine on symptoms, functioning, and quality of life for patients with GM2 - To evaluate the long-term safety and tolerability of N-Acetyl-L-Leucine at 4 g/day in patients aged =13 years, and weight-tiered doses in patients 6 to 12 years of age, with GM2 - To characterize the pharmacokinetics (PK) of N-Acetyl-L-Leucine in patients with GM2;Timepoint(s) of evaluation of this end point: 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 (Approximately day 84) The primary endpoint in this Extension Phase is success measured on the Clinical Impression of Change in Severity (CI-CS) from the Extension Phase baseline (Visit 7) to the end of treatment in the Extension Phase (Visit 9).;Primary end point(s): The primary endpoint for the study is based on blinded raters’ Clinical Impression of Change in Severi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Spinocerebellar Ataxia Functional Index (SCAFI) • Scale for Assessment and Rating of Ataxia (SARA) score • Quality of Life EQ-5D-5L for patients aged =18; EQ-5D-Y for patients aged <18 years (visual analogue scale; descriptive system) • Modified Disability Rating Scale (mDRS) • Treating Physician Clinical Global Impression of Severity (CGI-S) at every visit • Treating Physician Clinical Global Impression of Change (CGI-C) comparing end of treatment (Visit 4) to baseline (Visit 2), and end of washout (Visit 6) to end of treatment (Visit 4) • Caregiver Clinical Global Impression of Severity (CGI-S) at every visit • Caregiver Clinical Global Impression of Change (CGI-C) comparing end of treatment (Visit 4) to baseline (Visit 2), and end of washout (Visit 6) to end of treatment (Visit 4) • Patient Clinical Global Impression Scales Impression of Severity (CGI-S) at every visit if they are able • Patient Clinical Global Impression of Change (CGI-C) comparing end of treatment (Visit 4) to baseline (Visit 2), and end of washout (Visit 6) to end of treatment (Visit 4) if they are able For the extension phase: The Annual Severity Increment Score (ASIS) is included. The ASIS is a metric that measures the annual increment in clinical severity for individual patients providing a measure of the rate of disease progression in individual patients.;Timepoint(s) of evaluation of this end point: Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84) For the extension phase: Extension Phase Baseline (V7) to end of Extension Phase treatment with IB1001 ((Approximately Day 365 of the extension phase treatment). | — |
Countries
Germany, Spain, United Kingdom, United States
Contacts
Public ContactTaylor Fields
IntraBio Ltd
Outcome results
None listed