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

NCT ID: NCT04860960

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-20
• Study Completion Date: 2026-06-30

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.

Conditions

Niemann-Pick Disease, Type C1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Hydroxypropyl-beta-cyclodextrin

Intervention Type: DRUG

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

Placebo comparator

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.5N saline provided every 2 weeks intravenously

Open Label sub-study for Infants up to age 3

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.

Group Type: EXPERIMENTAL

Hydroxypropyl-beta-cyclodextrin

Intervention Type: DRUG

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

Interventions

Hydroxypropyl-beta-cyclodextrin

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

Intervention Type: DRUG

Placebo

0.5N saline provided every 2 weeks intravenously

Intervention Type: DRUG

Other Intervention Names

Trappsol Cyclo; 0.5N saline

Eligibility Criteria

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

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

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cyclo Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen Mullen, MD

Role: STUDY_DIRECTOR

Cyclo Therapeutics, Inc.

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

University of Florida

Jacksonville, Florida, United States

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

Hospital de Alta Complejidad en Red "El Cruce"

Buenos Aires, , Argentina

Hospital de Niños de la Santísima Trinidad

Córdoba, , Argentina

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

Parkville, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Metabolic Clinical Trials Unit

Adelaide, , 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

Höchheim, , Germany

University Munster

Münster, , Germany

Emek Medical Center-Department of Pediatrics

Afula, , Israel

Soroka Medical Center

Beersheba, , Israel

University of Catania

Catania, , Italy

Istituto Neurologico Carlo Besta

Milan, , Italy

University Hospital of Padova

Padua, , Italy

Centro di Coordinamento Regionale Malattie Rare

Udine, , Italy

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

MediPark

Warsaw, , Poland

King Faisal Specialist Hospital and Research Centre

Riyadh, , Saudi Arabia

Hospital Sant Joan de Déu - Neurology Department

Barcelona, , Spain

Hospital Universitari de Bellvitge

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

National Taiwan University Hospital

Taipei, , Taiwan

Gazi University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Ege University Medical School, Department of Inborn Errors of Metabolism

Izmir, , Turkey (Türkiye)

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

Birmingham, , United Kingdom

University College London

London, , United Kingdom

Salford Royal Foundation NHS Trust

Salford, , United Kingdom

Countries

United States; Argentina; Australia; Brazil; Germany; Israel; Italy; Poland; Saudi Arabia; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36279795 (View on PubMed)

Other Identifiers

CTD-TCNPC-301

Identifier Type: -

Identifier Source: org_study_id