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

Primary Purpose

GM2 Gangliosidosis, Tay-Sachs Disease, Sandhoff Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IB1001
Sponsored by
IntraBio Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GM2 Gangliosidosis

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 β-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 β-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 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.

    1. Aminopyridines (including sustained-release form);
    2. N-Acetyl-DL-Leucine (e.g. Tanganil®);
    3. N-Acetyl-L-Leucine (prohibited if not provided as IMP);
    4. Riluzole;
    5. Gabapentin;
    6. Varenicline;
    7. Chlorzoxazone;
    8. Sulfasalazine;
    9. Rosuvastatin.

Extension Phase Inclusion Criteria

  1. Completed Visit 6 of the IB1001-202 Parent Study
  2. The Principal Investigator determines further treatment with IB1001 to be in the patient's best interest
  3. Written informed consent signed by the patient and/or their legal representative/parent/ impartial witness for participation in the Extension Phase
  4. Patients are willing to continue to remain without the following prohibited medication from Visit 6 throughout the duration of the Extension Phase:

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.

Sites / Locations

  • University of California - Los Angeles
  • Mayo Clinic
  • NYU Langone School of Medicine
  • University of Giessen
  • Ludwig Maximilian University of Munich
  • Bellvitge University Hospital
  • Salford Trust
  • Royal Manchester Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treatment with IB1001

Post-Treatment Washout

Arm Description

Parent Study: 6-weeks treatment with IB1001 administered orally. Extension Phase: 1-year treatment with IB1001 administered orally. Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old will receive weight-tiered doses: Patients aged 6-12 years weighing 15 to <25 kg will take 2 g per day: 1 g in the morning and 1 g in the evening. Patients aged 6-12 years weighing 25 to <35 kg will take 3 g per day: 1 g in the morning, 1 g in the afternoon, and 1 g in the evening. Patients aged 6-12 years weighing ≥35 kg will take 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults)

After the Parent Study 6-week treatment period, and Extension Phase one-year treatment period, patients will enter a 6-week post-treatment washout period.

Outcomes

Primary Outcome Measures

Clinical Impression of Change in Severity (CI-CS)
The primary evaluation of the CI-CS will be performed by two independent neurologists whose assessments will be based on videos of the anchor test taken at each visit. These raters will be blinded to the treatment phases and the chronological order of the videos to reduce detection and performance bias. The CI-CS assessment will instruct the blinded rater to consider: 'compared to the first video, how has the severity of their performance on the 9HPT-D or 8MWT changed (improved or worsened) in 6-weeks as observed in the second video?' The CI-CS is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).

Secondary Outcome Measures

Spinocerebellar Ataxia Functional Index (SCAFI)
The SCAFI scale is a validated ataxia rating scale and is an objective measure of ataxia and physical functioning which consists of three sub-scales: the 8 Meter Walk Test (8MWT), the 9-hole peg test with both dominant and non-dominant hands (9HPT-D; 9HPT-ND) and the "PATA" test to measure speech performance. For the 8MWT and 9HPT tests, a lower score/time indicates a clinical improvement. A higher "PATA" test score indicates improvement in speech performance. The SCAFI total score, and three subscales (8MWT, 9HPT-D, and PATA) are reported for statistical analysis.
Scale for Assessment and Rating of Ataxia (SARA) score
The SARA scale is an eight-item clinical rating scale (gait, stance, sitting, speech, fine motor function and taxis) with a total score range of 0-40, where 0 is the best neurological status and 40 the worst. SARA is a reliable and validated clinical scale with a high internal consistency that measures the severity and progression of ataxia.
EuroQuol - 5 Dimension (EQ-5D) Quality of Life Scale
The EQ-5D is a standardized measure of health status consists of two parts: a multiple-choice questionnaire (descriptive system) and a visual analogue scale. The EQ-5D descriptive system comprises the following 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.
Modified Disability Rating Scale (mDRS)
The mDRS is used evaluate the overall neurological status. The scale assesses six domains (ambulation, manipulation, language, swallowing, seizures and ocular movements) and can be used to evaluate the severity of disease, monitor disease progression, and assess the effect of both symptomatic and long-term treatments. The mDRS scale is calculated as a composite score, with a lower score indicating an improved clinical status.
Investigator's Clinical Global Impressions (CGI)
The CGI Scale is a widely validated scale that long been implemented in neurodegenerative disease trials to provide an index of clinical importance that cannot be obtained from quantitative assessment measures. The CGI comprises of two companion one-item measures evaluating: (A) The severity of the patient's condition and (B) the change from the initiation of treatment. Both measures are evaluated on a 1 to 7 point Likert scale, with 1 indicating the best clinical status and 7 indicating the worst.
Parent/Caregiver's Clinical Global Impressions (CGI)
The CGI Scale is a widely validated scale that long been implemented in neurodegenerative disease trials to provide an index of clinical importance that cannot be obtained from quantitative assessment measures. The CGI comprises of two companion one-item measures evaluating: (A) The severity of the patient's condition and (B) the change from the initiation of treatment. Both measures are evaluated on a 1 to 7 point Likert scale, with 1 indicating the best clinical status and 7 indicating the worst.
Patient's Clinical Global Impressions (CGI) if able
The CGI Scale is a widely validated scale that long been implemented in neurodegenerative disease trials to provide an index of clinical importance that cannot be obtained from quantitative assessment measures. The CGI comprises of two companion one-item measures evaluating: (A) The severity of the patient's condition and (B) the change from the initiation of treatment. Both measures are evaluated on a 1 to 7 point Likert scale, with 1 indicating the best clinical status and 7 indicating the worst.

Full Information

First Posted
November 27, 2018
Last Updated
February 28, 2023
Sponsor
IntraBio Inc
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1. Study Identification

Unique Protocol Identification Number
NCT03759665
Brief Title
N-Acetyl-L-Leucine for GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease)
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
June 7, 2019 (Actual)
Primary Completion Date
January 9, 2023 (Actual)
Study Completion Date
January 9, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IntraBio Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). There are two phases to this study: the Parent Study, and the Extension Phase. The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the symptomatic treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of GM2 Gangliosidosis.
Detailed Description
In the Parent Study, Patients will be assessed during three study phases: a baseline period, a 6-week treatment period, and a 6-week post-treatment washout period. If within 6 weeks prior to the initial screening visit, a patient has received any of the prohibited medications defined in the eligibility criteria (irrespective of the preceding treatment duration) a wash-out study-run-in of 6 weeks is required prior to the first baseline assessment. All patients will receive the study drug during the treatment period. For each individual patient, the Parent Study lasts for approximately 3.5 - 4 months during which there are 6 visits to the study site. This Extension Phase allows patients who have completed the Parent Study to, at the discretion of the Principal Investigator (PI), continue treatment with N-Acetyl-L-Leucine (IB1001). Patients will receive treatment with IB1001 for two one-year treatment periods, separated by a 6-week washout. All patients will receive the study drug during these two one-year treatment periods. For each individual patient, the Extension Phase lasts for approximately 25.5 months, during which there are 6 visits to the study site.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GM2 Gangliosidosis, Tay-Sachs Disease, Sandhoff Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
In both the Parent Study and Extension Phase, patients will be assessed during three study phases: a baseline period (with or without a study run-in), a treatment period, and a washout period.
Masking
Outcomes Assessor
Masking Description
The primary evaluation of the Clinical Impression of Change in Severity (CI-CS; Primary Endpoint) will be performed by two independent neurologists whose assessments are based on videos of patient's performance on either the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or the 8 Meter Walk Test (8MWT) taken at each visit.
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment with IB1001
Arm Type
Experimental
Arm Description
Parent Study: 6-weeks treatment with IB1001 administered orally. Extension Phase: 1-year treatment with IB1001 administered orally. Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old will receive weight-tiered doses: Patients aged 6-12 years weighing 15 to <25 kg will take 2 g per day: 1 g in the morning and 1 g in the evening. Patients aged 6-12 years weighing 25 to <35 kg will take 3 g per day: 1 g in the morning, 1 g in the afternoon, and 1 g in the evening. Patients aged 6-12 years weighing ≥35 kg will take 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults)
Arm Title
Post-Treatment Washout
Arm Type
No Intervention
Arm Description
After the Parent Study 6-week treatment period, and Extension Phase one-year treatment period, patients will enter a 6-week post-treatment washout period.
Intervention Type
Drug
Intervention Name(s)
IB1001
Other Intervention Name(s)
N-Acetyl-L-Leucine
Intervention Description
IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered.
Primary Outcome Measure Information:
Title
Clinical Impression of Change in Severity (CI-CS)
Description
The primary evaluation of the CI-CS will be performed by two independent neurologists whose assessments will be based on videos of the anchor test taken at each visit. These raters will be blinded to the treatment phases and the chronological order of the videos to reduce detection and performance bias. The CI-CS assessment will instruct the blinded rater to consider: 'compared to the first video, how has the severity of their performance on the 9HPT-D or 8MWT changed (improved or worsened) in 6-weeks as observed in the second video?' The CI-CS is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).
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 Measure Information:
Title
Spinocerebellar Ataxia Functional Index (SCAFI)
Description
The SCAFI scale is a validated ataxia rating scale and is an objective measure of ataxia and physical functioning which consists of three sub-scales: the 8 Meter Walk Test (8MWT), the 9-hole peg test with both dominant and non-dominant hands (9HPT-D; 9HPT-ND) and the "PATA" test to measure speech performance. For the 8MWT and 9HPT tests, a lower score/time indicates a clinical improvement. A higher "PATA" test score indicates improvement in speech performance. The SCAFI total score, and three subscales (8MWT, 9HPT-D, and PATA) are reported for statistical analysis.
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)
Title
Scale for Assessment and Rating of Ataxia (SARA) score
Description
The SARA scale is an eight-item clinical rating scale (gait, stance, sitting, speech, fine motor function and taxis) with a total score range of 0-40, where 0 is the best neurological status and 40 the worst. SARA is a reliable and validated clinical scale with a high internal consistency that measures the severity and progression of ataxia.
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)
Title
EuroQuol - 5 Dimension (EQ-5D) Quality of Life Scale
Description
The EQ-5D is a standardized measure of health status consists of two parts: a multiple-choice questionnaire (descriptive system) and a visual analogue scale. The EQ-5D descriptive system comprises the following 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.
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)
Title
Modified Disability Rating Scale (mDRS)
Description
The mDRS is used evaluate the overall neurological status. The scale assesses six domains (ambulation, manipulation, language, swallowing, seizures and ocular movements) and can be used to evaluate the severity of disease, monitor disease progression, and assess the effect of both symptomatic and long-term treatments. The mDRS scale is calculated as a composite score, with a lower score indicating an improved clinical status.
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)
Title
Investigator's Clinical Global Impressions (CGI)
Description
The CGI Scale is a widely validated scale that long been implemented in neurodegenerative disease trials to provide an index of clinical importance that cannot be obtained from quantitative assessment measures. The CGI comprises of two companion one-item measures evaluating: (A) The severity of the patient's condition and (B) the change from the initiation of treatment. Both measures are evaluated on a 1 to 7 point Likert scale, with 1 indicating the best clinical status and 7 indicating the worst.
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)
Title
Parent/Caregiver's Clinical Global Impressions (CGI)
Description
The CGI Scale is a widely validated scale that long been implemented in neurodegenerative disease trials to provide an index of clinical importance that cannot be obtained from quantitative assessment measures. The CGI comprises of two companion one-item measures evaluating: (A) The severity of the patient's condition and (B) the change from the initiation of treatment. Both measures are evaluated on a 1 to 7 point Likert scale, with 1 indicating the best clinical status and 7 indicating the worst.
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)
Title
Patient's Clinical Global Impressions (CGI) if able
Description
The CGI Scale is a widely validated scale that long been implemented in neurodegenerative disease trials to provide an index of clinical importance that cannot be obtained from quantitative assessment measures. The CGI comprises of two companion one-item measures evaluating: (A) The severity of the patient's condition and (B) the change from the initiation of treatment. Both measures are evaluated on a 1 to 7 point Likert scale, with 1 indicating the best clinical status and 7 indicating the worst.
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Parent Study Inclusion Criteria Individuals who meet all of the following criteria are eligible to participate in the study: Written informed consent signed by the patient and/or their legal representative/ parent 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 β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes) at the time of signing informed consent. 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: intrauterine device (IUD); surgical sterilization of the partner (vasectomy for 6 months minimum); combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion. Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose: hysteroscopic sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy; 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. 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. If male, the patient agrees not to donate sperm from the first dose until 90 days after dosing. 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. Weight ≥15 kg at screening. 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: The Investigator does not believe the medication/therapy will interfere with the study protocol/results Patients have been on a stable dose/duration and type of therapy for at least 6 weeks before Visit 1 (Baseline 1) Patients are willing to maintain a stable dose/do not change their therapy throughout the duration of the study. 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: Asymptomatic patients 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 β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes Patients who have any of the following: Chronic diarrhea; Unexplained visual loss; Malignancies; Insulin-dependent diabetes mellitus. Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or derivatives. History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose, sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan, dimethicone, methylparaben, and potassium sorbate). 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. 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. Known clinically-significant (at the discretion of the investigator) laboratories in hematology, coagulation, clinical chemistry, or urinalysis, including, but not limited to: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper limit of normal (ULN); Total bilirubin >1.5x ULN, unless Gilbert's syndrome is present in which case total bilirubin >2x ULN. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol. Current or planned pregnancy or women who are breastfeeding. 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. 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. 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. Aminopyridines (including sustained-release form); N-Acetyl-DL-Leucine (e.g. Tanganil®); N-Acetyl-L-Leucine (prohibited if not provided as IMP); Riluzole; Gabapentin; Varenicline; Chlorzoxazone; Sulfasalazine; Rosuvastatin. Extension Phase Inclusion Criteria Completed Visit 6 of the IB1001-202 Parent Study The Principal Investigator determines further treatment with IB1001 to be in the patient's best interest Written informed consent signed by the patient and/or their legal representative/parent/ impartial witness for participation in the Extension Phase Patients are willing to continue to remain without the following prohibited medication from Visit 6 throughout the duration of the Extension Phase: 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.
Facility Information:
Facility Name
University of California - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
NYU Langone School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
University of Giessen
City
Gießen
ZIP/Postal Code
35389
Country
Germany
Facility Name
Ludwig Maximilian University of Munich
City
München
ZIP/Postal Code
80539
Country
Germany
Facility Name
Bellvitge University Hospital
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Salford Trust
City
Salford
State/Province
Greater Manchester
ZIP/Postal Code
M5 5AP
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34349180
Citation
Churchill GC, Strupp M, Factor C, Bremova-Ertl T, Factor M, Patterson MC, Platt FM, Galione A. Acetylation turns leucine into a drug by membrane transporter switching. Sci Rep. 2021 Aug 4;11(1):15812. doi: 10.1038/s41598-021-95255-5.
Results Reference
derived
PubMed Identifier
33482890
Citation
Fields T, Patterson M, Bremova-Ertl T, Belcher G, Billington I, Churchill GC, Davis W, Evans W, Flint S, Galione A, Granzer U, Greenfield J, Karl R, Kay R, Lewi D, Mathieson T, Meyer T, Pangonis D, Platt FM, Tsang L, Verburg C, Factor M, Strupp M. A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia. Trials. 2021 Jan 22;22(1):84. doi: 10.1186/s13063-020-05009-3.
Results Reference
derived

Learn more about this trial

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

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