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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05163288




Registration number
NCT05163288
Ethics application status
Date submitted
6/12/2021
Date registered
20/12/2021

Titles & IDs
Public title
A Pivotal Study of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C
Scientific title
Effects of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C (NPC): A Phase III, Randomized, Placebo-controlled, Double-blind, Crossover Study
Secondary ID [1] 0 0
IB1001-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Niemann-Pick Disease, Type C 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Dementias
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - N-Acetyl-L-Leucine
Other interventions - Placebo

Experimental: N-acetyl-L-leucine (IB1001) - Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients =13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day); patients \<13 will receive weight-tiered doses.

Placebo comparator: Placebo comparator - Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients =13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day); patients \<13 will receive weight-tiered doses.


Treatment: Drugs: N-Acetyl-L-Leucine
N-Acetyl-L-Leucine is a modified amino-acid ester that is orally administered (granules for suspension in a sachet)

Other interventions: Placebo
Matching Placebo Sachet
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Scale for the Assessment and Rating of Ataxia (all jurisdictions except US)
Timepoint [1] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)
Primary outcome [2] 0 0
Modified Scale for the Assessment and Rating of Ataxia (US only)
Timepoint [2] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)
Secondary outcome [1] 0 0
Spinocerebellar Ataxia Functional Index (SCAFI)
Timepoint [1] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)
Secondary outcome [2] 0 0
Modified Disability Rating Scale
Timepoint [2] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)
Secondary outcome [3] 0 0
Physician's / Caregiver's / Patient's Clinical Global Impressions (CGI)
Timepoint [3] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)
Secondary outcome [4] 0 0
EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale
Timepoint [4] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)
Secondary outcome [5] 0 0
Scale for the Assessment and Rating of Ataxia (US only)
Timepoint [5] 0 0
End of Period I (week 12) vs. End of Period 2 (week 24)

Eligibility
Key inclusion criteria
1. Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness
2. Male or female aged =4 years with a confirmed genetic diagnosis of NPC 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 and confirm to continue 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 who 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, patient agrees not to donate sperm from the first dose until 90 days after their last dose.
7. Patients must fall within:

a) A SARA score of 7 = X = 34 points (out of 40) AND b) Either: i. Within the 2-7 range (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 NPC including those on the prohibited medication list. Non-prohibited medications/therapies (authorized medicines for NPC [e.g. miglustat], 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 42 days 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).
Minimum age
4 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who are unable to consistently Patients who have any known hypersensitivity or history of hypersensitivity to:

1. Acetyl-Leucine (DL-, L-, D-) or derivatives.
2. Excipients the IB1001 sachet (namely isomalt, hypromellose, and strawberry flavour).
3. Excipients the placebo sachet (namely isomalt, hypromellose, strawberry flavour, citric acid, microcrystalline cellulose, lactose, denatonium benzoate).
2. Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; 'study drug') for at least 42 days prior to Visit 1. At the discretion of the investigator, Medical Monitor, and Sponsor, the washout period for specific IMPs may be longer based on the pharmacological activity and pharmacokinetics of the drug.
3. Patients with a physical, cognitive, 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.
4. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.
5. Current or planned pregnancy or women who are breastfeeding.
6. 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.
7. 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.
8. Patients unwilling and/or not able to undergo a 42 day period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6.

1. N-Acetyl-DL-Leucine (e.g. Tanganil®);
2. N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-301 trial);
3. Sulfasalazine;
4. Rosuvastatin.

-

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2024
Actual
Sample size
Target
53
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Minnesota
Country [2] 0 0
Czechia
State/province [2] 0 0
Praha
Country [3] 0 0
Germany
State/province [3] 0 0
Gießen
Country [4] 0 0
Germany
State/province [4] 0 0
Hamburg
Country [5] 0 0
Germany
State/province [5] 0 0
Hochheim
Country [6] 0 0
Germany
State/province [6] 0 0
München
Country [7] 0 0
Germany
State/province [7] 0 0
Münster
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Slovakia
State/province [9] 0 0
Bratislava
Country [10] 0 0
Switzerland
State/province [10] 0 0
Bern
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
IntraBio Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The results of the study will be published within a reasonable timeframe of completion. Pseudonymised individual patient data may be available in these findings.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results not provided in https://clinicaltrials.gov/study/NCT05163288