N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC)
- Conditions
- Niemann-Pick Disease, Type C
- Interventions
- Drug: IB1001
- Registration Number
- NCT03759639
- 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 Niemann-Pick type C disease (NPC).
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 NPC.
The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of NPC.
- 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 the 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 33
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment with IB1001 IB1001 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)
- Primary Outcome Measures
Name Time Method Clinical Impression of Change in Severity (CI-CS) [Fields et al 2021] CI-CS comparing Baseline (Day 1) with IB1001 versus 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) versus the end of 6-weeks post-treatment washout The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: 'compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video?'
The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).
- Secondary Outcome Measures
Name Time Method Key Secondary Endpoint: Change in Severity Based on Average CI-S CI-CS comparing baseline period and end of treatment period minus the change in CI-S between end of treatment period and end of washout period. The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: 'compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video?' The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).
Modified Disability Rating Scale (mDRS) [Iturriaga et al. 2006] Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout Overall neurological status based on six domains (ambulation, manipulation, language, swallowing, seizures and ocular movements). The Modified Disability Rating Scale ranges from 0-24, where 0 is the best neurological status and 24 is the worst.
Key Secondary Endpoint: CI-CS Score Reclassified on a 3-Point Scale Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment);End of treatment with IB1001 to the end of post 6-week treatment washout The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: 'compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video?' The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).
CI-CS scores \<0 were reclassified as worsened (-1), CI-CS scores 0 remained classified as not changed (0), and CI-CS scores \>0 were reclassified as improved (+1).Key Secondary Endpoint: CI-CS Score for the Non-Primary Anchor Test CI-CS of the non-primary anchor test was evaluated, comparing the CI-CS of Visit 4 versus Visit 2 and of Visit 6 versus Visit 4 as done for the primary anchor test. The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).
EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale: Visual Analogue Scale (VAS) Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout For posting, health-related quality of life based on the EQ-5D visual analogue scale (VAS) was presented as a secondary endpoint.
EQ-5D VAS is a 0-100 scale where patients are asked to indicate their overall health, with a score of 0 indicating worst health and a score of 100 indicating best health.Key Secondary Endpoint: Individual Components of the CI-CS Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment);End of treatment with IB1001 to the end of post 6-week treatment washout The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: 'compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video?' The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).
Spinocerebellar Ataxia Functional Index (SCAFI) [Schmitz-Hübsch et al, 2008] Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout Spinocerebellar Ataxia Functional Index (SCAFI) is composed of 8 Meter Walk Test, 9-Hole Peg Test of Dominant and Non-Dominant Hand (9HPT-D/9HPT-ND) (the 3 tests are timed assessments; each is done twice and values are averaged; the 8MWT and 9HPT-D and 9HPT-ND values are converted from times to rates, and the results expressed as a composite Z-score of each test relative to baseline) and the PATA rate (counted number how often a patient can repeat the syllables "PATA" within 10 seconds), a measure of speech performance. The scores of these 3 were transformed to Z-scores (=individual's average of both trials to perform the respective task - mean of study population at baseline) / SD of study population at baseline). A Z-score of 0 equates to the population mean at baseline. For all 3, higher Z-scores (above mean) mean better performance. The SCAFI total score was calculated as the arithmetic mean of the non-missing Z-scores for the 3. A higher total score means better performance.
Scale for Assessment and Rating of Ataxia (SARA) Score [Schmitz-Hübsch et al, 2006; Subramony, 2007] Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout The Scale for Assessment and Rating of Ataxia has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. The range is 0-40 points, with a lower score representing neurological improvement and a higher score representing neurological worsening.
Investigator's Clinical Global Impressions of Change (CGI-C) Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout The Clinical Global Impression of Change assessed by the investigator is evaluated on a 7 point Likert scale ranging from 1='very much improved' to 7='very much worse'
Parent/Caregiver's Clinical Global Impression of Change (CGI-C) Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout The Clinical Global Impression of Change assessed by the parent/caregiver is evaluated on a 7 point Likert scale ranging from 1='very much improved' to 7='very much worse'.
Patient's Clinical Global Impressions (CGI) if Able Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout The Clinical Global Impression of Change assessed by the patient (if able) is evaluated on a 7 point Likert scale ranging from 1='very much improved' to 7='very much worse'.
Trial Locations
- Locations (9)
Comenius University in Bratislva
🇸🇰Bratislava, Slovakia
Bellvitge University Hospital
🇪🇸Barcelona, Spain
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Giessen
🇩🇪Gießen, Germany
Ludwig Maximilian University of Munich
🇩🇪München, Germany
Great Ormond Street Hospital
🇬🇧London, United Kingdom
Salford Trust
🇬🇧Salford, Greater Manchester, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom