Clinical trial • Phase III • Neurology|Rare Disease
L-ACETYLLEUCINE for Niemann-Pick disease type C
Phase III trial of L-ACETYLLEUCINE for Niemann-Pick disease type C.
Overview
- Trial Therapeutic Area
- Neurology|Rare Disease
- Trial Disease
- Niemann-Pick disease type C
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 26-01-2024
- First CTIS Authorization Date
- 26-03-2024
Trial design
Randomised, placebo (granules for oral suspension) as comparator in a randomized, placebo-controlled, double-blind crossover design; active treatment n-acetyl-l-leucine (ib1001) dosing: up to 4 g/day in patients aged ≥13 years, weight-tiered doses for patients aged 4 to 12 years. specific placebo dosing schedule not stated., crossover Phase III trial across 6 sites in Czechia, Germany, Netherlands and others.
- Randomised
- Yes
- Comparator
- Placebo (Granules for oral suspension) as comparator in a randomized, placebo-controlled, double-blind crossover design; active treatment N-Acetyl-L-Leucine (IB1001) dosing: up to 4 g/day in patients aged ≥13 years, weight-tiered doses for patients aged 4 to 12 years. Specific placebo dosing schedule not stated.
- Crossover
- Yes
- Target Sample Size
- 60
- Trial Duration For Participant
- 116
Eligibility
Recruits 60 paediatric patients.
- Vulnerable Population
- Vulnerable populations are included (isVulnerablePopulationSelected = true). Consent may be provided by the patient and/or their legal representative/parent/impartial witness ("Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness"). Assent and age-specific informed consent documents are provided (documented ICFs and assent forms for ages 12-14, age-specific ICFs for children 6-11, 12-16, under 7, and parent/guardian ICFs). Multiple translated ICF/addenda versions are available for different countries/languages to support consent/assent.
Inclusion criteria
- {"criterion_text":"- Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness"}
- {"criterion_text":"- Male or female aged ≥4 years with a confirmed diagnosis of NPC at the time of signing informed consent"}
- {"criterion_text":"- Patients must fall within: a)\\tA SARA score of 7 ≤ X ≤ 34 points (out of 40) AND b)\\tEither: i.\\tWithin the 2-7 range (0-8 range) of the Gait subtest of the SARA scale OR ii.\\tBe able to perform the 9-Hole Peg Test with Dominant Hand (9HPT-D) (SCAFI subtest) in 20 ≤ X ≤150 seconds."}
- {"criterion_text":"- Weight ≥15 kg at screening"}
Exclusion criteria
- {"criterion_text":"- Patients who have any known hypersensitivity or history of hypersensitivity to Acetyl leucine (DL, L, D) or derivatives, and or Excipients in the IB1001 or placebo sachets"}
- {"criterion_text":"- Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product"}
- {"criterion_text":"- Patients with a physical or psychiatric condition which, at the investigator’s discretion and in consultation with the Medical Monitor and Sponsor (as applicable), may put the patient at risk, may confound the study results, or may interfere with the patient’s participation in the clinical study, i.e. reliably perform study assessments"}
- {"criterion_text":"- 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"}
Endpoints
Primary endpoints
- {"endpoint_text":"- The primary endpoint for the study is of the Scale for the Assessment and Rating of Ataxia (SARA). In the US, the Modified SARA is the primary endpoint.","definition_or_measurement_approach":"Efficacy evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) in all jurisdictions except the US; in the US the Modified SARA (mSARA) is used as the primary measurement."}
Secondary endpoints
- {"endpoint_text":"- Spinocerebellar Ataxia Functional Index (SCAFI)","definition_or_measurement_approach":"SCAFI scoring/form included as a functional index for ataxia-related performance (standard SCAFI assessments/forms referenced)."}
- {"endpoint_text":"- Quality of Life EQ-5D-5L for patients aged ≥18; EQ-5D-Y for patients aged <18 years","definition_or_measurement_approach":"Health-related quality of life measured using EQ-5D-5L for adults (≥18) and EQ-5D-Y for children (<18)."}
- {"endpoint_text":"- Modified Disability Rating Scale (mDRS)","definition_or_measurement_approach":"Disability assessed using the Modified Disability Rating Scale (mDRS) per protocol scoring forms."}
- {"endpoint_text":"- Physician’s, Caregiver’s (if applicable), and Patient’s (if able) Clinical Global Impression of Improvement (CGI-I) comparing end of period I (Visit 4) to baseline (Visit 2), and end of period II (Visit 6) to end of period I (Visit 4)","definition_or_measurement_approach":"Clinical Global Impression of Improvement (CGI-I) ratings by physician, caregiver and patient (if able) comparing specified visits (Visit 4 vs Visit 2; Visit 6 vs Visit 4) per CGI-I scoring forms."}
Recruitment
- Planned Sample Size
- 60
- Recruitment Window Months
- 89
- Consent Approach
- Written informed consent must be signed by the patient and/or their legal representative/parent/impartial witness. Age-specific consent/assent processes are used: parental/guardian consent for minors and assent forms for children (examples: Assent Ages 12-14, EP Pathway documents for ages 6-11, 12-17, under 7). Multiple ICF addenda and translated versions (examples in documents: Czech, German, Italian, Greek, Portuguese, Ukrainian, Croatian, Dutch) are provided to participants and parents as appropriate.
Geography
- Total Number Of Sites
- 6
- Total Number Of Participants
- 60
Czechia
- Earliest CTIS Part Ii Submission Date
- 12-12-2023
- Latest Decision Or Authorization Date
- 27-03-2024
- Processing Time Days
- 107
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Vseobecna Fakultni Nemocnice V Praze
- Department Name
- Klinika pediatrie a dědičných poruch metabolismu
- Contact Person Name
- Stella Reichmannova
- Contact Person Email
- Stella.Reichmannova@vfn.cz
Germany
- Earliest CTIS Part Ii Submission Date
- 12-12-2023
- Latest Decision Or Authorization Date
- 16-09-2025
- Processing Time Days
- 644
- Number Of Sites
- 3
- Number Of Participants
- 28
Sites
- Site Name
- SphinCS GmbH
- Department Name
- Clinical Science in LDS
- Contact Person Name
- Eugen Mengel
- Contact Person Email
- eugen.mengel@sphincs.de
- Site Name
- Universitaet Muenster
- Department Name
- Stoffwechsellabor der Kinderklinik
- Contact Person Name
- Thorsten Marquardt
- Contact Person Email
- marquat@uni-munster.de
- Site Name
- Justus-Liebig-Universitaet Giessen
- Department Name
- Neurology
- Contact Person Name
- Kyriakos Martakis
- Contact Person Email
- Kyriakos.Martakis@paediat.med.uni-giessen.de
Netherlands
- Earliest CTIS Part Ii Submission Date
- 12-12-2023
- Latest Decision Or Authorization Date
- 26-03-2024
- Processing Time Days
- 471
- Number Of Sites
- 1
- Number Of Participants
- 20
Sites
- Site Name
- Academisch Medisch Centrum
- Department Name
- metabole ziekten
- Contact Person Name
- Marion Brands
- Contact Person Email
- m.m.brands@amsterdamumc.nl
Slovakia
- Earliest CTIS Part Ii Submission Date
- 12-12-2023
- Latest Decision Or Authorization Date
- 17-09-2025
- Processing Time Days
- 645
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Comenius University Bratislava
- Department Name
- Neurology
- Contact Person Name
- Miriam Kolnikova
- Contact Person Email
- kolnikova@dfnsp.sk
Sponsor
Primary sponsor
- Full Name
- Intrabio Limited
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United Kingdom
Investigational products
- Investigational Product Name
- N-Acetyl-L-Leucine
- Active Substance
- L-ACETYLLEUCINE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- EU MP number PRD7972387 (prodAuthStatus:1)
- Orphan Designation
- Yes
- Dose Levels
- 4 g/day for patients aged ≥13 years; weight-tiered doses for patients aged 4 to 12 years
- Frequency
- 4 g/day (total daily dose); weight-tiered dosing frequency as per protocol for ages 4-12
- Maximum Dose
- 4 g/day
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