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Trial record 1 of 4 for:    N-acetyl-L-leucine
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A Pivotal Study of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C

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ClinicalTrials.gov Identifier: NCT05163288
Recruitment Status : Recruiting
First Posted : December 20, 2021
Last Update Posted : July 7, 2022
Sponsor:
Information provided by (Responsible Party):
IntraBio Inc

Brief Summary:
A pivotal, randomized, double-blind, placebo controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of Niemann Pick disease type C (NPC). The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.

Condition or disease Intervention/treatment Phase
Niemann-Pick Disease, Type C Drug: N-Acetyl-L-Leucine Other: Placebo Phase 3

Detailed Description:

This is a multinational, randomized, placebo-controlled, double-blinded, cross-over Phase III study that will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) versus Placebo for the treatment of Niemann-Pick type C disease (NPC).

Patients will be assessed during three study periods: a baseline period (approximately 2-weeks), after which they will be randomized (1:1) to receive treatment with IB1001 or Placebo for approximately 12-weeks during the first intervention period ("Period I"). Following Period I, patients will crossover to receive the opposite treatment (IB1001 or Placebo) for approximately 12-weeks during a second intervention period ("Period II).

Patients will be assessed twice during each study period. Patients who have participated in the study may be offered the opportunity to roll over into an Extension Phase, which is planned to allow patients to have further access to IB1001.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, placebo-controlled, double-blind, crossover, multi-center, study with 1:1 randomization of IB1001 plus SOC for 12-weeks versus placebo plus SOC for 12-weeks, followed by open-label extension study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C (NPC): A Phase III, Randomized, Placebo-controlled, Double-blind, Crossover Study
Actual Study Start Date : June 30, 2022
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
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.
Drug: 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 Name: IB1001

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.
Other: Placebo
Matching Placebo Sachet




Primary Outcome Measures :
  1. Scale for the Assessment and Rating of Ataxia (all jurisdictions except US) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  2. Modified Scale for the Assessment and Rating of Ataxia (US only) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]

Secondary Outcome Measures :
  1. Spinocerebellar Ataxia Functional Index (SCAFI) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  2. Modified Disability Rating Scale [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  3. Physician's / Caregiver's / Patient's Clinical Global Impressions (CGI) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  4. EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  5. Scale for the Assessment and Rating of Ataxia (US only) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]

Other Outcome Measures:
  1. Niemann-Pick disease type C Clinical Severity Scale (NPC-CSS) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  2. 5-Domain Niemann-Pick disease type C Clinical Severity Scale (NPC-CSS) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  3. Investigator's / Caregiver's / Patient's Clinical Global Impressions (CGI) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]
  4. Modified Scale for the Assessment and Rating of Ataxia (all jurisdictions except US) [ Time Frame: End of Period I (week 12) vs. End of Period 2 (week 24) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

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.

      -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05163288


Contacts
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Contact: Michael Strupp, MD +44 8081 641283 mstrupp@intrabio.com
Contact: Taylor Fields +44 8081 641283 tfields@intrabio.com

Locations
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United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Ami Rosen       arosen3@emory.edu   
Principal Investigator: William Wilcox, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Bridget Neja    507-538-4107    Neja.bridget@mayo.edu   
Principal Investigator: Antony Fine, MD         
Australia, Victoria
The Royal Melbourne Hospital Not yet recruiting
Parkville, Victoria, Australia, 3050
Contact: Mark Walterfang, MD    +61 (0) 3 9342 4657    mark.walterfang@gmail.com   
Principal Investigator: Mark Walterfang, MD         
Czechia
First Faculty of Medicine, Charles University Hospital Prague Not yet recruiting
Praha, Czechia, 128 08
Contact: Stella Mazurová, MD       Stella.Mazurova@vfn.cz   
Principal Investigator: Stella Mazurová, MD         
Germany
University of Giessen Recruiting
Gießen, Germany, 35389
Contact: Kyriakos Martakis, MD    +49 (0)641 985 43543    Kyriakos.Martakis@paediat.med.uni-giessen.de   
Sub-Investigator: Andreas Hahn, MD         
Principal Investigator: Kyriakos Martakis, MD         
University of Hamburg Recruiting
Hamburg, Germany, 20246
Contact: Nicole Muschol, MD       muschol@uke.de   
Principal Investigator: Nicole Muschol, MD         
SphinCS - Institute of Clinical Science in Lysosomal Storage Disorders Not yet recruiting
Hochheim, Germany, 65239
Contact: Eugen Mengel, MD       info@sphincs.de   
Principal Investigator: Eugen Mengel, MD         
Ludwig Maximilian University of Munich Not yet recruiting
München, Germany, 80539
Contact: Susanne Schneider-Pils, MD    +49 (0)89 4400 7677    susanne.schneider@med.uni-muenchen.de   
Principal Investigator: Susanne Schneider-Pils, MD         
University Hospital Münster Recruiting
Münster, Germany, 48149
Contact: Anja Wolf       Anja.Wolf@ukmuenster.de   
Principal Investigator: Thorsten Marquardt, MD         
Netherlands
Amsterdam UMC Recruiting
Amsterdam, Netherlands, 1105
Contact: Marion Brands, MD       m.m.brands@amsterdamumc.nl   
Principal Investigator: Marion Brands, MD         
Slovakia
Comenius University in Bratislva Recruiting
Bratislava, Slovakia, 833 40
Contact: Katarína Cichovská    +421 2 59371 274    katarina.cichovska@dfnsp.sk   
Principal Investigator: Miriam Koníková, MUDr, PhD         
Sub-Investigator: Tomáš Foltán, MUDr         
Switzerland
University Hospital Bern Inselspital Not yet recruiting
Bern, Switzerland, 3010
Contact: Tatiana Bremova-Ertl, MD, PhD       tatiana.bremova-ertl@insel.ch   
Principal Investigator: Tatiana Bremova-Ertl, MD, PhD         
United Kingdom
Salford Trust Not yet recruiting
Salford, Greater Manchester, United Kingdom, M5 5AP
Contact: Marie Meehan    +44 161 206 4192    Marie.Meehan@srft.nhs.uk   
Principal Investigator: Reena Sharma, MD         
Great Ormond Street Hospital Not yet recruiting
London, United Kingdom, WC1N 3JH
Contact: Olivia Rosie-Wilkinson    0207 405 9200 ext 4727    Olivia.Rosie-Wilkinson@gosh.nhs.uk   
Principal Investigator: Paul Gissen, MD         
Royal Free London NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Masoud Kazemi    +44 (0) 207 830 2814    masod.kazemi@nhs.net   
Principal Investigator: Uma Ramaswami, MD         
Royal Manchester Children's Hospital Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Laura Crowther    +44161 701 9137    laura.crowther@mft.nhs.uk   
Principal Investigator: Simon Jones, MD         
Sponsors and Collaborators
IntraBio Inc
Publications of Results:
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Responsible Party: IntraBio Inc
ClinicalTrials.gov Identifier: NCT05163288    
Other Study ID Numbers: IB1001-301
First Posted: December 20, 2021    Key Record Dates
Last Update Posted: July 7, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The results of the study will be published within a reasonable timeframe of completion. Pseudonymised individual patient data may be available in these findings.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Frontotemporal Lobar Degeneration
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases