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

Phase 3

Active, not recruiting

• Conditions: Niemann-Pick Disease, Type C1
• Interventions: Drug: Hydroxypropyl-beta-cyclodextrin; Drug: Placebo

• Registration Number: NCT04860960
• Lead Sponsor: Cyclo Therapeutics, Inc.

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.

Detailed Description

The TransportNPC study is a prospective, randomized, double-blind, placebo controlled therapeutic study for 93 patients age 3 and older with confirmed diagnosis of 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 by slow infusion every two weeks in addition to standard of care as compared to placebo and standard of care. Standard of care may include Miglustat or leucine products that are not currently under investigation as a therapeutic. Patients will be randomized to receive Trappsol Cyclo or placebo at a 2:1 ratio. The study duration is 96 weeks, with an unblinded interim analysis at 48 weeks. An open-label extension of up to 96 weeks follows the interventional study. Patients whose disease progression worsens by two levels in the Clinical Global Impression of Severity scale over 12 weeks, starting at week 36, may be moved to open label treatment. Efficacy will be measured at week 48 and week 96 by a composite score of major disease features. A sub-study will be conducted in countries following EMA guidance for up to 12 patients age 0 - 3 years who may be asymptomatic. Outcomes for the sub-study are safety, clinical and caregiver impression of disease.

Study Timeline

• Study First Submitted: 2021-04-15
• Study First Submitted QC: 2021-04-22
• Study First Posted: 2021-04-27
• Study Start: 2021-07-20
• Status Verified: 2023-09
• Last Update Submitted: 2024-06-03
• Last Update Posted: 2024-06-04
• Primary Completion: 2025-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

1. Confirmed diagnosis of NPC1
2. Annual Severity Increment Score between 0.5 and 2.0 using the 17-domain NPC Severity Scale
3. 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).
4. Body weight greater than 4.5 kg and less than or equal to 125 kg
5. Presenting at least 1 neurological symptom of the disease
6. Written informed consent
7. Willing and capable to participate in all aspects of trial design
8. Ability to travel to the trial site at scheduled times
9. Contraception requirements per protocol
10. Caregiver consent as appropriate to participate in all protocol-specified assessments for duration of trial
11. Inclusion criteria for Open Label Extension are 1) Received double-blind treatment for at least 48 weeks with CGI-S deterioration by at least 2 levels for 2 consecutive assessment visits 12 weeks apart, or 2) completion of double-blind treatment and completed all assessments through week 96, or 3) Discontinued early from double-blind treatment but completed all assessments through week 96
12. Inclusion criteria for patients age 0 to 3 years in open-label sub-study in countries following EMA guidance only: Confirmed diagnosis of NPC1; treated or not with Miglustat per main study; body weight greater than 4.5kg; patient may be asymptomatic; written assent for child to participate in safety assessments; caregiver consent to participate in caregiver assessments; ability to travel to the trial site for all scheduled visits.

Exclusion Criteria

1. Recipient of a liver transplant within <12 months or planned liver transplantation
2. Patients with active liver disease from any cause other than NPC1
3. Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or international normalized ratio > 1.8
4. Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate <60ml/min/1.73m2.
5. Use of curcumin or fish oil within 12 weeks prior to enrollment
6. Known or suspected allergy or intolerance to the study treatment
7. In the opinion of the Investigator, the patient's clinical condition does not allow for the blood collection required as per protocol specific procedures.
8. 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
9. Treatment with any other investigational drug during the study
10. Pregnancy or breastfeeding
11. 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)
12. 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.
13. Neurologically asymptomatic patients
14. Inability to participate in the primary study assessment (4D-NPC-SS or 5D-NPC-SS) as determined by the Investigator
15. Exclusion criteria for patients age 0 to 3 years in open-label sub-study in countries following EMA guidance only are similar to the main study with the addition of exclusion criterion of history of fetal hydrops or fetal ascites

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	Hydroxypropyl-beta-cyclodextrin	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
Placebo comparator	Placebo	Intravenous administration of 0.5N saline over at least 6.5 hours every 2 weeks
Open Label sub-study for Infants up to age 3	Hydroxypropyl-beta-cyclodextrin	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.

Primary Outcome Measures

Name	Time	Method
Change from Baseline in 4-Domain NPC Severity Score (US only)	End of Study at Week 96	Ambulation, Fine Motor, Speech, Swallow
Change from Baseline in 5-Domain NPC Severity Score (ex-US)	End of Study at Week 96	Ambulation, Fine Motor, Speech, Swallow, Cognition

Secondary Outcome Measures

Name	Time	Method
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	Vineland Adaptive Behavior Scale II
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	SCAFI
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	PAS

Trial Locations

Locations (35)

Emory; 🇺🇸 Atlanta, Georgia, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

UPMC Children's Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University Utah; 🇺🇸 Salt Lake City, Utah, United States

Lysosomal and Rare Disorders Research & Treatment Center, Inc.; 🇺🇸 Fairfax, Virginia, United States

UCSF Benioff Children's Hospital Oakland; 🇺🇸 Oakland, California, United States

Hospital de Niños de la Santísima Trinidad; 🇦🇷 Córdoba, Argentina

Szpital Uniwersytecki w Krakowie; 🇵🇱 Kraków, Poland

University of Florida; 🇺🇸 Jacksonville, Florida, United States

Soroka Medical Center; 🇮🇱 Be'er Sheva, Israel

MediPark; 🇵🇱 Warsaw, Poland

King Faisal Specialist Hospital and Research Centre; 🇸🇦 Riyadh, Saudi Arabia

Hospital de Alta Complejidad en Red "El Cruce"; 🇦🇷 Buenos Aires, Argentina

Melbourne Children's Trials Centre Murdoch Children's Research Institute; 🇦🇺 Parkville, Victoria, Australia

Metabolic Clinical Trials Unit; 🇦🇺 Adelaide, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Universidade de São Paulo; 🇧🇷 São Paulo, Brazil

University of Campinas; 🇧🇷 São Paulo, Brazil

SphinCS GmbH; 🇩🇪 Hochheim, Germany

Emek Medical Center-Department of Pediatrics; 🇮🇱 Afula, Israel

University Munster; 🇩🇪 Münster, Germany

University of Catania; 🇮🇹 Catania, Italy

Centro di Coordinamento Regionale Malattie Rare; 🇮🇹 Udine, Italy

Istituto Neurologico Carlo Besta; 🇮🇹 Milan, Italy

University Hospital of Padova; 🇮🇹 Padova, Italy

Hospital Sant Joan de Déu - Neurology Department; 🇪🇸 Barcelona, Spain

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Hospital Universitari de Bellvitge; 🇪🇸 Barcelona, Spain

Gazi University Faculty of Medicine; 🇹🇷 Ankara, Turkey

University College London; 🇬🇧 London, United Kingdom

Salford Royal Foundation NHS Trust; 🇬🇧 Salford, United Kingdom

Ege University Medical School, Department of Inborn Errors of Metabolism; 🇹🇷 İzmir, Turkey

Birmingham Children's Hospital NHS Foundation Trust · Department of Inherited Metabolic Disorders Service; 🇬🇧 Birmingham, United Kingdom

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain