A Pivotal Study of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C

NCT05163288 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IB1001-301
• Study Type: interventional
• Target: 53
• Locations: 8 countries
• Sites: 14

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. Following this randomized, double-blind, placebo-controlled "Parent Study", an extension phase is conducted for (1) patients who completed the "Parent Study" and (2) patients who are enrolled directly into the Extension Phase. Currently, the Extension Phase provides patients with 3 years of open-label treatment.

Conditions

Niemann-Pick Disease, Type C

Outcome Measures

Primary Outcomes (2)

• Scale for the Assessment and Rating of Ataxia (all jurisdictions except US)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Modified Scale for the Assessment and Rating of Ataxia (US only)

  End of Period I (week 12) vs. End of Period 2 (week 24)

Secondary Outcomes (5)

• Spinocerebellar Ataxia Functional Index (SCAFI)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Modified Disability Rating Scale

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Physician's / Caregiver's / Patient's Clinical Global Impressions (CGI)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Scale for the Assessment and Rating of Ataxia (US only)

  End of Period I (week 12) vs. End of Period 2 (week 24)

Other Outcomes (4)

• Niemann-Pick disease type C Clinical Severity Scale (NPC-CSS)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• 5-Domain Niemann-Pick disease type C Clinical Severity Scale (NPC-CSS)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Investigator's / Caregiver's / Patient's Clinical Global Impressions (CGI)

  End of Period I (week 12) vs. End of Period 2 (week 24)

Study Arms (2)

N-acetyl-L-leucine (IB1001)

EXPERIMENTAL

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

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

Interventions

N-Acetyl-L-Leucine DRUG

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

Also known as: IB1001

N-acetyl-L-leucine (IB1001)

Placebo OTHER

Matching Placebo Sachet

Placebo comparator

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness
• Male or female aged ≥4 years with a confirmed genetic diagnosis of NPC at the time of signing informed consent.
• 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:
• intrauterine device (IUD);
• surgical sterilization of the partner (vasectomy for 6 months minimum);
• combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
• progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
• intrauterine hormone releasing system (IUS);
• bilateral tubal occlusion.
• Females of non-childbearing potential who have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
• hysteroscopic sterilization;
• bilateral tubal ligation or bilateral salpingectomy;
• hysterectomy;
• 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.
• 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.

You may not qualify if:

• Patients who are unable to consistently Patients who have any known hypersensitivity or history of hypersensitivity to:
• Acetyl-Leucine (DL-, L-, D-) or derivatives.
• Excipients the IB1001 sachet (namely isomalt, hypromellose, and strawberry flavour).
• Excipients the placebo sachet (namely isomalt, hypromellose, strawberry flavour, citric acid, microcrystalline cellulose, lactose, denatonium benzoate).
• 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.
• 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.
• Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.
• Current or planned pregnancy or women who are breastfeeding.
• 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.
• 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.
• 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.
• N-Acetyl-DL-Leucine (e.g. Tanganil®);
• N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-301 trial);
• Sulfasalazine;
• Rosuvastatin.

Sponsors & Collaborators

• IntraBio Inc: lead

Study Sites (14)

Mayo Clinic

Rochester, Minnesota, 55905, United States

COMPLETED

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

ACTIVE NOT RECRUITING

First Faculty of Medicine, Charles University Hospital Prague

Prague, 128 08, Czechia

ACTIVE NOT RECRUITING

University of Giessen

Giessen, 35389, Germany

ACTIVE NOT RECRUITING

University of Hamburg

Hamburg, 20246, Germany

COMPLETED

SphinCS - Institute of Clinical Science in Lysosomal Storage Disorders

Höchheim, 65239, Germany

ACTIVE NOT RECRUITING

Ludwig Maximilian University of Munich

München, 80539, Germany

NOT YET RECRUITING

University Hospital Münster

Münster, 48149, Germany

ACTIVE NOT RECRUITING

Amsterdam UMC

Amsterdam, 1105, Netherlands

RECRUITING

Comenius University in Bratislva

Bratislava, 833 40, Slovakia

ACTIVE NOT RECRUITING

University Hospital Bern Inselspital

Bern, 3010, Switzerland

ACTIVE NOT RECRUITING

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

ACTIVE NOT RECRUITING

Royal Free London NHS Foundation Trust

London, United Kingdom

ACTIVE NOT RECRUITING

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

ACTIVE NOT RECRUITING

Related Publications (5)

• Bremova-Ertl T, Claassen J, Foltan T, Gascon-Bayarri J, Gissen P, Hahn A, Hassan A, Hennig A, Jones SA, Kolnikova M, Martakis K, Raethjen J, Ramaswami U, Sharma R, Schneider SA. Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C. J Neurol. 2022 Mar;269(3):1651-1662. doi: 10.1007/s00415-021-10717-0. Epub 2021 Aug 13.

  PMID: 34387740 BACKGROUND

• Kaya E, Smith DA, Smith C, Morris L, Bremova-Ertl T, Cortina-Borja M, Fineran P, Morten KJ, Poulton J, Boland B, Spencer J, Strupp M, Platt FM. Acetyl-leucine slows disease progression in lysosomal storage disorders. Brain Commun. 2020 Dec 20;3(1):fcaa148. doi: 10.1093/braincomms/fcaa148. eCollection 2021.

  PMID: 33738443 BACKGROUND

• Cortina-Borja M, Te Vruchte D, Mengel E, Amraoui Y, Imrie J, Jones SA, I Dali C, Fineran P, Kirkegaard T, Runz H, Lachmann R, Bremova-Ertl T, Strupp M, Platt FM. Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials. Orphanet J Rare Dis. 2018 Aug 16;13(1):143. doi: 10.1186/s13023-018-0880-9.

  PMID: 30115089 BACKGROUND

• Patterson MC, Ramaswami U, Donald A, Foltan T, Gautschi M, Gissen P, Hahn A, Jones SA, Kay R, Kolnikova M, Park J, Reichmannova S, Walterfang M, Wibawa P, Rohrbach M, Martakis K, Bremova-Ertl T. Disease-Modifying, Neuroprotective Effect of N-Acetyl-l-Leucine in Adult and Pediatric Patients With Niemann-Pick Disease Type C. Neurology. 2025 Jul;105(1):e213589. doi: 10.1212/WNL.0000000000213589. Epub 2025 Jun 13.

  PMID: 40513057 DERIVED

• Bremova-Ertl T, Ramaswami U, Brands M, Foltan T, Gautschi M, Gissen P, Gowing F, Hahn A, Jones S, Kay R, Kolnikova M, Arash-Kaps L, Marquardt T, Mengel E, Park JH, Reichmannova S, Schneider SA, Sivananthan S, Walterfang M, Wibawa P, Strupp M, Martakis K. Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C. N Engl J Med. 2024 Feb 1;390(5):421-431. doi: 10.1056/NEJMoa2310151.

  PMID: 38294974 DERIVED

MeSH Terms

Conditions

Niemann-Pick Disease, Type C

Interventions

acetylleucine; IB1001

Condition Hierarchy (Ancestors)

Niemann-Pick Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Michael Strupp, MD

CONTACT

+44 8081 641283; mstrupp@intrabio.com

Taylor Fields

CONTACT

+44 8081 641283; tfields@intrabio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: December 20, 2021
• Study Start: June 30, 2022
• Primary Completion: June 12, 2023
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); DE (5); NL (1); US (1); AU (1); GB (3); CZ (1); SL (1)