<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03759665</url>
  </required_header>
  <id_info>
    <org_study_id>IB1001-202</org_study_id>
    <nct_id>NCT03759665</nct_id>
  </id_info>
  <brief_title>N-Acetyl-L-Leucine for GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IntraBio Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IntraBio Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study&#xD;
      which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of&#xD;
      GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease).&#xD;
&#xD;
      There are two phases to this study: the Parent Study, and the Extension Phase.&#xD;
&#xD;
      The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the&#xD;
      symptomatic treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease).&#xD;
&#xD;
      The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the&#xD;
      neuroprotective, disease-modifying treatment of GM2 Gangliosidosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the Parent Study, Patients will be assessed during three study phases: a baseline period,&#xD;
      a 6-week treatment period, and a 6-week post-treatment washout period. If within 6 weeks&#xD;
      prior to the initial screening visit, a patient has received any of the prohibited&#xD;
      medications defined in the eligibility criteria (irrespective of the preceding treatment&#xD;
      duration) a wash-out study-run-in of 6 weeks is required prior to the first baseline&#xD;
      assessment. All patients will receive the study drug during the treatment period. For each&#xD;
      individual patient, the Parent Study lasts for approximately 3.5 - 4 months during which&#xD;
      there are 6 visits to the study site.&#xD;
&#xD;
      This Extension Phase allows patients who have completed the Parent Study to, at the&#xD;
      discretion of the Principal Investigator (PI), continue treatment with N-Acetyl-L-Leucine&#xD;
      (IB1001). Patients will receive treatment with IB1001 for two one-year treatment periods,&#xD;
      separated by a 6-week washout. All patients will receive the study drug during these two&#xD;
      one-year treatment periods. For each individual patient, the Extension Phase lasts for&#xD;
      approximately 25.5 months, during which there are 6 visits to the study site.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 7, 2019</start_date>
  <completion_date type="Actual">January 9, 2023</completion_date>
  <primary_completion_date type="Actual">January 9, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Impression of Change in Severity (CI-CS)</measure>
    <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</time_frame>
    <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.&#xD;
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?'&#xD;
The CI-CS is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Spinocerebellar Ataxia Functional Index (SCAFI)</measure>
    <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 &amp; Extension Phase - 42 days following end of treatment)</time_frame>
    <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 &quot;PATA&quot; test to measure speech performance.&#xD;
For the 8MWT and 9HPT tests, a lower score/time indicates a clinical improvement. A higher &quot;PATA&quot; test score indicates improvement in speech performance.&#xD;
The SCAFI total score, and three subscales (8MWT, 9HPT-D, and PATA) are reported for statistical analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Scale for Assessment and Rating of Ataxia (SARA) score</measure>
    <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 &amp; Extension Phase - 42 days following end of treatment)</time_frame>
    <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.&#xD;
SARA is a reliable and validated clinical scale with a high internal consistency that measures the severity and progression of ataxia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQuol - 5 Dimension (EQ-5D) Quality of Life Scale</measure>
    <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 &amp; Extension Phase - 42 days following end of treatment)</time_frame>
    <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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Disability Rating Scale (mDRS)</measure>
    <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)</time_frame>
    <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.&#xD;
The mDRS scale is calculated as a composite score, with a lower score indicating an improved clinical status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator's Clinical Global Impressions (CGI)</measure>
    <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 &amp; Extension Phase - 42 days following end of treatment)</time_frame>
    <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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parent/Caregiver's Clinical Global Impressions (CGI)</measure>
    <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 &amp; Extension Phase - 42 days following end of treatment)</time_frame>
    <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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's Clinical Global Impressions (CGI) if able</measure>
    <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 &amp; Extension Phase - 42 days following end of treatment)</time_frame>
    <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.&#xD;
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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>GM2 Gangliosidosis</condition>
  <condition>Tay-Sachs Disease</condition>
  <condition>Sandhoff Disease</condition>
  <arm_group>
    <arm_group_label>Treatment with IB1001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Parent Study: 6-weeks treatment with IB1001 administered orally. Extension Phase: 1-year treatment with IB1001 administered orally.&#xD;
Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day).&#xD;
Patients 6-12 years old will receive weight-tiered doses:&#xD;
Patients aged 6-12 years weighing 15 to &lt;25 kg will take 2 g per day: 1 g in the morning and 1 g in the evening.&#xD;
Patients aged 6-12 years weighing 25 to &lt;35 kg will take 3 g per day: 1 g in the morning, 1 g in the afternoon, and 1 g in the evening.&#xD;
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)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Post-Treatment Washout</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IB1001</intervention_name>
    <description>IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered.</description>
    <arm_group_label>Treatment with IB1001</arm_group_label>
    <other_name>N-Acetyl-L-Leucine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Parent Study Inclusion Criteria&#xD;
&#xD;
        Individuals who meet all of the following criteria are eligible to participate in the&#xD;
        study:&#xD;
&#xD;
          1. Written informed consent signed by the patient and/or their legal representative/&#xD;
             parent&#xD;
&#xD;
          2. Male or female aged ≥6 years in Europe OR ≥18 years in the United States with a&#xD;
             confirmed diagnosis of GM2 Gangliosidosis ( i.e., clinical features and positive&#xD;
             genetic test GM2-gangliosidosis caused by β-hexosaminidase deficiency resulting from&#xD;
             mutations in the HEXA or HEXB genes) at the time of signing informed consent.&#xD;
&#xD;
          3. Females of childbearing potential, defined as a premenopausal female capable of&#xD;
             becoming pregnant, will be included if they are either sexually inactive (sexually&#xD;
             abstinent for 14 days prior to the first dose continuing through 28 days after the&#xD;
             last dose) or using one of the following highly effective contraceptives (i.e. results&#xD;
             in &lt;1% failure rate when used consistently and correctly) 14 days prior to the first&#xD;
             dose continuing through 28 days after the last dose:&#xD;
&#xD;
               1. intrauterine device (IUD);&#xD;
&#xD;
               2. surgical sterilization of the partner (vasectomy for 6 months minimum);&#xD;
&#xD;
               3. combined (estrogen or progestogen containing) hormonal contraception associated&#xD;
                  with the inhibition of ovulation (either oral, intravaginal, or transdermal);&#xD;
&#xD;
               4. progestogen-only hormonal contraception associated with the inhibition of&#xD;
                  ovulation (either oral, injectable, or implantable);&#xD;
&#xD;
               5. intrauterine hormone-releasing system (IUS);&#xD;
&#xD;
               6. bilateral tubal occlusion.&#xD;
&#xD;
          4. Females of non-childbearing potential must have undergone one of the following&#xD;
             sterilization procedures at least 6 months prior to the first dose:&#xD;
&#xD;
               1. hysteroscopic sterilization;&#xD;
&#xD;
               2. bilateral tubal ligation or bilateral salpingectomy;&#xD;
&#xD;
               3. hysterectomy;&#xD;
&#xD;
               4. bilateral oophorectomy;&#xD;
&#xD;
             OR&#xD;
&#xD;
             be postmenopausal with amenorrhea for at least 1 year prior to the first dose and&#xD;
             follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.&#xD;
             FSH analysis for postmenopausal women will be done at screening. FSH levels should be&#xD;
             in the postmenopausal range as determined by the central laboratory.&#xD;
&#xD;
          5. Non-vasectomized male patient agrees to use a condom with spermicide or abstain from&#xD;
             sexual intercourse during the study until 90 days beyond the last dose of study&#xD;
             medication and the female partner agrees to comply with inclusion criteria 3 or 4. For&#xD;
             a vasectomized male who has had his vasectomy 6 months or more prior to study start,&#xD;
             it is required that they use a condom during sexual intercourse. A male who has been&#xD;
             vasectomized less than 6 months prior to study start must follow the same restrictions&#xD;
             as a non-vasectomized male.&#xD;
&#xD;
          6. If male, the patient agrees not to donate sperm from the first dose until 90 days&#xD;
             after dosing.&#xD;
&#xD;
          7. Patients must fall within:&#xD;
&#xD;
             a) A SARA score of 5 ≤ X ≤ 33 points (out of 40) AND i. Within the 2-7 range (out of&#xD;
             0-8 range) of the Gait subtest of the SARA scale OR ii. Be able to perform the 9 Hole&#xD;
             Peg Test with Dominant Hand (9HPT-D) (SCAFI subtest) in 20 ≤ X ≤150 seconds.&#xD;
&#xD;
          8. Weight ≥15 kg at screening.&#xD;
&#xD;
          9. Patients are willing to disclose their existing medications/therapies for (the&#xD;
             symptoms) of GM2 Gangliosidosis, including those on the prohibited medication list.&#xD;
             Non-prohibited medications/therapies (e.g. concomitant speech therapy, and&#xD;
             physiotherapy) are permitted provided:&#xD;
&#xD;
               1. The Investigator does not believe the medication/therapy will interfere with the&#xD;
                  study protocol/results&#xD;
&#xD;
               2. Patients have been on a stable dose/duration and type of therapy for at least 6&#xD;
                  weeks before Visit 1 (Baseline 1)&#xD;
&#xD;
               3. Patients are willing to maintain a stable dose/do not change their therapy&#xD;
                  throughout the duration of the study.&#xD;
&#xD;
         10. An understanding of the implications of study participation, provided in the written&#xD;
             patient information and informed consent by patients or their legal&#xD;
             representative/parent, and demonstrates a willingness to comply with instructions and&#xD;
             attend required study visits (for children this criterion will also be assessed in&#xD;
             parents or appointed guardians).&#xD;
&#xD;
        Parent Study Exclusion Criteria&#xD;
&#xD;
        Individuals who meet any of the following criteria are not eligible to participate in the&#xD;
        study:&#xD;
&#xD;
          1. Asymptomatic patients&#xD;
&#xD;
          2. Patient has clinical features of Tay-Sachs or Sandhoff disease, but a completely&#xD;
             negative result on a previous genetic test for GM2 Gangliosidosis caused by&#xD;
             β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes&#xD;
&#xD;
          3. Patients who have any of the following:&#xD;
&#xD;
               1. Chronic diarrhea;&#xD;
&#xD;
               2. Unexplained visual loss;&#xD;
&#xD;
               3. Malignancies;&#xD;
&#xD;
               4. Insulin-dependent diabetes mellitus.&#xD;
&#xD;
               5. Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or&#xD;
                  derivatives.&#xD;
&#xD;
               6. History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose,&#xD;
                  sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan,&#xD;
                  dimethicone, methylparaben, and potassium sorbate).&#xD;
&#xD;
          4. Simultaneous participation in another clinical study or participation in any clinical&#xD;
             study involving administration of an investigational medicinal product (IMP; 'study&#xD;
             drug') within 6 weeks prior to Visit 1.&#xD;
&#xD;
          5. Patients with a physical or psychiatric condition which, at the investigator's&#xD;
             discretion, may put the patient at risk, may confound the study results, or may&#xD;
             interfere with the patient's participation in the clinical study.&#xD;
&#xD;
          6. Known clinically-significant (at the discretion of the investigator) laboratories in&#xD;
             hematology, coagulation, clinical chemistry, or urinalysis, including, but not limited&#xD;
             to:&#xD;
&#xD;
               1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt;5x upper&#xD;
                  limit of normal (ULN);&#xD;
&#xD;
               2. Total bilirubin &gt;1.5x ULN, unless Gilbert's syndrome is present in which case&#xD;
                  total bilirubin &gt;2x ULN.&#xD;
&#xD;
          7. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.&#xD;
&#xD;
          8. Current or planned pregnancy or women who are breastfeeding.&#xD;
&#xD;
          9. Patients with severe vision or hearing impairment (that is not corrected by glasses or&#xD;
             hearing aids) that, at the investigator's discretion, interferes with their ability to&#xD;
             perform study assessments.&#xD;
&#xD;
         10. Patients who have been diagnosed with arthritis or other musculoskeletal disorders&#xD;
             affecting joints, muscles, ligaments, and/or nerves that by themselves affects&#xD;
             patient's mobility and, at the investigator's discretion, interferes with their&#xD;
             ability to perform study assessments.&#xD;
&#xD;
         11. Patients unwilling and/or not able to undergo a 6-week washout period from any of the&#xD;
             following prohibited medication prior to Visit 1 (Baseline 1) and remain without&#xD;
             prohibited medication through Visit 6.&#xD;
&#xD;
               1. Aminopyridines (including sustained-release form);&#xD;
&#xD;
               2. N-Acetyl-DL-Leucine (e.g. Tanganil®);&#xD;
&#xD;
               3. N-Acetyl-L-Leucine (prohibited if not provided as IMP);&#xD;
&#xD;
               4. Riluzole;&#xD;
&#xD;
               5. Gabapentin;&#xD;
&#xD;
               6. Varenicline;&#xD;
&#xD;
               7. Chlorzoxazone;&#xD;
&#xD;
               8. Sulfasalazine;&#xD;
&#xD;
               9. Rosuvastatin.&#xD;
&#xD;
        Extension Phase Inclusion Criteria&#xD;
&#xD;
          1. Completed Visit 6 of the IB1001-202 Parent Study&#xD;
&#xD;
          2. The Principal Investigator determines further treatment with IB1001 to be in the&#xD;
             patient's best interest&#xD;
&#xD;
          3. Written informed consent signed by the patient and/or their legal&#xD;
             representative/parent/ impartial witness for participation in the Extension Phase&#xD;
&#xD;
          4. Patients are willing to continue to remain without the following prohibited medication&#xD;
             from Visit 6 throughout the duration of the Extension Phase:&#xD;
&#xD;
        Aminopyridines (including sustained-release form); b) N-Acetyl-DL-Leucine (e.g. Tanganil®);&#xD;
        c) N-Acetyl-L-Leucine (prohibited if not provided as IMP); d) Riluzole; e) Gabapentin; f)&#xD;
        Varenicline; g) Chlorzoxazone; h) Sulfasalazine; i) Rosuvastatin.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of California - Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Giessen</name>
      <address>
        <city>Gießen</city>
        <zip>35389</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ludwig Maximilian University of Munich</name>
      <address>
        <city>München</city>
        <zip>80539</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bellvitge University Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salford Trust</name>
      <address>
        <city>Salford</city>
        <state>Greater Manchester</state>
        <zip>M5 5AP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Manchester Children's Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gangliosidoses</mesh_term>
    <mesh_term>Tay-Sachs Disease</mesh_term>
    <mesh_term>Gangliosidoses, GM2</mesh_term>
    <mesh_term>Sandhoff Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03759665
org study id: IB1001-202
nct id: NCT03759665
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention 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.
primary purpose: Treatment
masking: Single (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.
measure: 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
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).
measure: 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)
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.
measure: 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)
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.
measure: 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)
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.
measure: 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)
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.
measure: 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)
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.
measure: 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)
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.
measure: 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)
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.
arm group label: Treatment with IB1001
arm group type: Experimental
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 group label: Post-Treatment Washout
arm group type: No Intervention
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: IB1001
description: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered.
arm group label: Treatment with IB1001
other name: N-Acetyl-L-Leucine
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
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country: Germany
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Gangliosidoses
mesh term: Tay-Sachs Disease
mesh term: Gangliosidoses, GM2
mesh term: Sandhoff Disease