N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T)
- Conditions
- Ataxia TelangiectasiaLouis Bar Syndrome
- Interventions
- Drug: IB1001
- Registration Number
- NCT03759678
- Lead Sponsor
- IntraBio Inc
- 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 Ataxia-Telangiectasia (A-T).
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) for the symptomatic treatment of A-T.
The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of A-T.
- Detailed Description
The primary purpose of the study is to evaluate the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the treatment of A-T investigating the efficacy in terms of improving symptoms, functioning, and quality of life against the defined endpoints in patients with A-T.
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 this study.
For each individual patient, the study lasts for approximately 3.5 - 4 months during which there are 6 study 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 the treatment period. For each individual patient, the Extension Phase lasts for approximately 25.5 months, during which there are 6 visits to the study site.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment with IB1001 IB1001 6-weeks 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 6-week treatment period, patients will enter a 6-week post-treatment washout period.
- Primary Outcome Measures
Name Time Method Clinical Impression of Change in Severity (CI-CS) 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 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
Name Time Method Spinocerebellar Ataxia Functional Index (SCAFI) 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) The SCAFI scale is a validated ataxia rating scale and is an objective measure of ataxia and physical functioning which consists of three subscales: 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.Patient's Clinical Global Impressions (CGI) if able 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) 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.Investigator's Clinical Global Impressions (CGI) 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) 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.Change in the Scale for Assessment and Rating of Ataxia (SARA) score 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) 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 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) 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.Parent/Caregiver's Clinical Global Impressions (CGI) 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) 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.
Trial Locations
- Locations (5)
University of California - Los Angeles
🇺🇸Los Angeles, California, United States
University of Giessen
🇩🇪Gießen, Germany
Ludwig Maximilian University of Munich
🇩🇪München, Germany
Royal Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Hospital Universitario La Paz
🇪🇸Madrid, Spain