Phase 3 Study to Evaluate Intravenous Trappsol(R) Cyclo(TM) in Pediatric and Adult Patients With Niemann-Pick Disease Type C1

NCT04860960 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CTD-TCNPC-301
• Study Type: interventional
• Target: 94
• Locations: 13 countries
• Sites: 35

Brief Summary

A prospective, randomized, double-blind, placebo controlled, multi-center therapeutic study for patients age 3 and older with confirmed diagnosis of Niemann Pick disease type C1 (NPC1). The objective of this study is to evaluate the safety, tolerability and efficacy of 2000 mg/kg dose of Trappsol Cyclo (hydroxypropyl betacyclodextrin) administered intravenously compared to standard of care. An open-label sub-study in countries following European Medicines Agency (EMA) guidance will enroll asymptomatic or symptomatic patients from infancy up to age 3 to evaluate safety in that population.

Conditions

Niemann-Pick Disease, Type C1

Keywords

NPC1; cyclodextrin; Niemann-Pick; Niemann-Pick Type C; NPC; Niemann Pick C; Niemann Pick Type C; Niemann Pick

Outcome Measures

Primary Outcomes (4)

• Change from Baseline in 4-Domain NPC Severity Score (US only)

  Ambulation, Fine Motor, Speech, Swallow

  Interim Analysis at Week 48

• Change from Baseline in 4-Domain NPC Severity Score (US only)

  Ambulation, Fine Motor, Speech, Swallow

  End of Study at Week 96

• Change from Baseline in 5-Domain NPC Severity Score (ex-US)

  Ambulation, Fine Motor, Speech, Swallow, Cognition

  Interim Analysis at Week 48

• Change from Baseline in 5-Domain NPC Severity Score (ex-US)

  Ambulation, Fine Motor, Speech, Swallow, Cognition

  End of Study at Week 96

Secondary Outcomes (4)

• Change in ataxia as measured by Spinocerebellar ataxia functional index

  Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192

• Change in adaptive behavior as measured by Vineland Adaptive Behavior Scale II

  Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192

• Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale

  Change from Baseline measured at Interim Analysis Week 48

• Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale

  Change from Baseline measured at End of Study Week 96

Other Outcomes (8)

• Change in speaking ability compared to Baseline as measured by voice recordings collected in SpeechVitals mobile device application

  Baseline and every two weeks through week 192

• Change in speaking ability compared to Pre-Infusion as measured by voice recordings collected in SpeechVitals mobile device application

  Every two weeks through week 192

• Change in Scores of Clinical Global Impression of Severity and of Change compared to Baseline

  Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192

Study Arms (3)

Experimental

EXPERIMENTAL

Intravenous administration of 2000 mg/kg hydroxypropyl betacyclodextrin (Trappsol Cyclo) (based on body weight) diluted with 0.5N saline over at least 6.5 hours every 2 weeks

Drug: Hydroxypropyl-beta-cyclodextrin

Placebo comparator

PLACEBO COMPARATOR

Intravenous administration of 0.5N saline over at least 6.5 hours every 2 weeks

Drug: Placebo

Open Label sub-study for Infants up to age 3

EXPERIMENTAL

Up to 12 patients age 0 - 3 yrs in countries following EMA guidance may be enrolled in this open label sub-study. All patients will receive 2000 mg/kg hydroxypropyl betacyclodextrin (Trappsol Cyclo) diluted with 0.5N saline at the clinician's discretion over 6.5 hours every 2 weeks. Outcome measures are safety, clinician and caregiver impressions.

Drug: Hydroxypropyl-beta-cyclodextrin

Interventions

Hydroxypropyl-beta-cyclodextrin DRUG

Dose is 2000 mg/kg body weight provided every 2 weeks intravenously

Also known as: Trappsol Cyclo

Experimental; Open Label sub-study for Infants up to age 3

Placebo DRUG

0.5N saline provided every 2 weeks intravenously

Also known as: 0.5N saline

Placebo comparator

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of NPC1
• Annual Severity Increment Score between 0.5 and 2.0 using the 17-domain NPC Severity Scale
• Treated or Not Treated with Miglustat (patients must be on a stable dose for at least 3 months prior to the Screening Visit, or have discontinued Miglustat for at least 3 months prior to Screening Visit).
• Body weight greater than 4.5 kg and less than or equal to 125 kg
• Presenting at least 1 neurological symptom of the disease
• Written informed consent
• Willing and capable to participate in all aspects of trial design
• Ability to travel to the trial site at scheduled times
• Contraception requirements per protocol
• Caregiver consent as appropriate to participate in all protocol-specified assessments for duration of trial

You may not qualify if:

• Recipient of a liver transplant within \<12 months or planned liver transplantation
• Patients with active liver disease from any cause other than NPC1
• Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or international normalized ratio \> 1.8
• Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate \<60ml/min/1.73m2.
• Use of curcumin or fish oil within 12 weeks prior to enrollment
• Known or suspected allergy or intolerance to the study treatment
• In the opinion of the Investigator, the patient's clinical condition does not allow for the blood collection required as per protocol specific procedures.
• Treatment with any investigational drug during the 3 months prior to entering the study. If the investigational drug has a short half-life (\<8 hours) and would be expected to be cleared from the body within 1 month, then the wash-out period is 1 month. Treatment with any form of leucine, whether as an investigational drug or other formulation is not allowed
• Treatment with any other investigational drug during the study
• Pregnancy or breastfeeding
• Current participation in another trial is not permitted unless it is a noninterventional study and the sole purpose of the trial is for long-term follow up describing clinical features or survival data (registry)
• Patients with uncontrolled, severe epileptic seizure periods (at least 3 consecutive severe epileptic seizures that required medication) within 2 months prior to completion of informed consent or assent, as applicable.
• Neurologically asymptomatic patients
• Inability to participate in the primary study assessment (4D-NPC-SS or 5D-NPC-SS) as determined by the Investigator

Sponsors & Collaborators

• Cyclo Therapeutics, Inc.: lead

Study Sites (35)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

University of Florida

Jacksonville, Florida, 32207, United States

Location

Emory

Atlanta, Georgia, 30322, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

UPMC Children's Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

University Utah

Salt Lake City, Utah, 84108, United States

Location

Lysosomal and Rare Disorders Research & Treatment Center, Inc.

Fairfax, Virginia, 22030, United States

Location

Hospital de Alta Complejidad en Red "El Cruce"

Buenos Aires, Argentina

Location

Hospital de Niños de la Santísima Trinidad

Córdoba, Argentina

Location

Melbourne Children's Trials Centre Murdoch Children's Research Institute

Parkville, Victoria, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, Australia

Location

Metabolic Clinical Trials Unit

Adelaide, Australia

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Location

Universidade de São Paulo

São Paulo, Brazil

Location

University of Campinas

São Paulo, Brazil

Location

SphinCS GmbH

Höchheim, Germany

Location

University Munster

Münster, Germany

Location

Emek Medical Center-Department of Pediatrics

Afula, Israel

Location

Soroka Medical Center

Beersheba, Israel

Location

University of Catania

Catania, Italy

Location

Istituto Neurologico Carlo Besta

Milan, Italy

Location

University Hospital of Padova

Padua, Italy

Location

Centro di Coordinamento Regionale Malattie Rare

Udine, Italy

Location

Szpital Uniwersytecki w Krakowie

Krakow, Poland

Location

MediPark

Warsaw, Poland

Location

King Faisal Specialist Hospital and Research Centre

Riyadh, Saudi Arabia

Location

Hospital Sant Joan de Déu - Neurology Department

Barcelona, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Gazi University Faculty of Medicine

Ankara, Turkey (Türkiye)

Location

Ege University Medical School, Department of Inborn Errors of Metabolism

Izmir, Turkey (Türkiye)

Location

Birmingham Children's Hospital NHS Foundation Trust · Department of Inherited Metabolic Disorders Service

Birmingham, United Kingdom

Location

University College London

London, United Kingdom

Location

Salford Royal Foundation NHS Trust

Salford, United Kingdom

Location

Related Publications (1)

• Hastings C, Liu B, Hurst B, Cox GF, Hrynkow S. Intravenous 2-hydroxypropyl-beta-cyclodextrin (Trappsol(R) Cyclo) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial. Mol Genet Metab. 2022 Dec;137(4):309-319. doi: 10.1016/j.ymgme.2022.10.004. Epub 2022 Oct 17.

  PMID: 36279795 DERIVED

MeSH Terms

Conditions

Niemann-Pick Disease, Type C

Interventions

2-Hydroxypropyl-beta-cyclodextrin

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

Intervention Hierarchy (Ancestors)

beta-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Study Officials

• Karen Mullen, MD

  Cyclo Therapeutics, Inc.

  STUDY DIRECTOR

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, multi-center, double-blind and parallel group study with 2:1 randomization of Trappsol Cyclo plus SOC versus placebo plus SOC over 96 weeks, followed by open-label extension study of 96 weeks

Study Record Dates

• First Submitted: April 15, 2021
• First Posted: April 27, 2021
• Study Start: July 20, 2021
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 4, 2024

Record last verified: 2023-09

Locations

AR (2); AU (3); BR (3); IL (2); IT (4); SA (1); ES (3); TW (1); TU (2); GB (3); US (7); DE (2); PL (2)