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

Niemann-Pick Disease, Type C1 Clinical Trial

— TransportNPC  

Official title:

Phase 3, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of 2000mg/kg of Trappsol®Cyclo™ (Hydroxypropyl-B-cyclodextrin) and Standard of Care Compared to Placebo and Standard of Care in Patients With Niemann-Pick Disease Type C1 (TransportNPC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04860960
• Other study ID #: CTD-TCNPC-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 20, 2021
• Est. completion date: June 2026

Study information

• Verified date: September 2023
• Source: Cyclo Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 94
• Est. completion date: June 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Frontotemporal Dementia
• Niemann-Pick Disease, Type C
• Niemann-Pick Disease, Type C1
• Niemann-Pick Diseases
• Pick Disease of the Brain

Intervention

Drug:
• Hydroxypropyl-beta-cyclodextrin
Dose is 2000 mg/kg body weight provided every 2 weeks intravenously
• Placebo
0.5N saline provided every 2 weeks intravenously

Locations

Country	Name	City	State
Argentina	Hospital de Alta Complejidad en Red "El Cruce"	Buenos Aires
Argentina	Hospital de Niños de la Santísima Trinidad	Córdoba
Australia	Metabolic Clinical Trials Unit	Adelaide
Australia	Melbourne Children's Trials Centre Murdoch Children's Research Institute	Parkville	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Universidade de São Paulo	São Paulo
Brazil	University of Campinas	São Paulo
Germany	SphinCS GmbH	Hochheim
Germany	University Munster	Münster
Israel	Emek Medical Center-Department of Pediatrics	Afula
Israel	Soroka Medical Center	Be'er Sheva
Italy	University of Catania	Catania
Italy	Istituto Neurologico Carlo Besta	Milan
Italy	University Hospital of Padova	Padova
Italy	Centro di Coordinamento Regionale Malattie Rare	Udine
Poland	Szpital Uniwersytecki w Krakowie	Kraków
Poland	MediPark	Warsaw
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
Spain	Hospital Sant Joan de Déu - Neurology Department	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Gazi University Faculty of Medicine	Ankara
Turkey	Ege University Medical School, Department of Inborn Errors of Metabolism	Izmir
United Kingdom	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 States	Emory	Atlanta	Georgia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Lysosomal and Rare Disorders Research & Treatment Center, Inc.	Fairfax	Virginia
United States	University of Florida	Jacksonville	Florida
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	UPMC Children's Hospital	Pittsburgh	Pennsylvania
United States	University Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Cyclo Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Germany,  Israel,  Italy,  Poland,  Saudi Arabia,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in speaking ability compared to Baseline as measured by voice recordings collected in SpeechVitals mobile device application	Measurement of speech features including articulatory precision, speaking and pause rates	Baseline and every two weeks through week 192
Other	Change in speaking ability compared to Pre-Infusion as measured by voice recordings collected in SpeechVitals mobile device application	Measurement of speech features including articulatory precision, speaking and pause rates within 24 hours post-infusion	Every two weeks through week 192
Other	Change in Scores of Clinical Global Impression of Severity and of Change compared to Baseline	Clinical Global Impression of Severity and of Change	Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192
Other	Change in Scores of Caregiver Global Impression of Severity and of Change scales	Caregiver Global Impression of Severity and of Change	Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192
Other	Caregiver Global Impression of Change at 24 hours post infusion	Caregiver Global Impression of Change at 24 hours post infusion	Baseline and every 2 weeks through week 192
Other	Change from Baseline in Respiratory function measured by Forced Expiratory Volume in 1 second	FEV1	Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 192
Other	Change from Baseline in Liver function as measured by liver enzyme assessments	Liver function measured by liver enzyme assessments including alanine and aspartate aminotransferases	Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192
Other	Safety assessments to include incidence of Adverse Events and Serious Adverse Events	Incidence of AEs, SAEs, incidence of abnormal laboratory test results, abnormal ECGs, abnormal physical exams, abnormal vital signs and abnormal hearing assessments assessments	Regular assessments per protocol through week 192
Primary	Change from Baseline in 4-Domain NPC Severity Score (US only)	Ambulation, Fine Motor, Speech, Swallow	Interim Analysis at Week 48
Primary	Change from Baseline in 4-Domain NPC Severity Score (US only)	Ambulation, Fine Motor, Speech, Swallow	End of Study at Week 96
Primary	Change from Baseline in 5-Domain NPC Severity Score (ex-US)	Ambulation, Fine Motor, Speech, Swallow, Cognition	Interim Analysis at Week 48
Primary	Change from Baseline in 5-Domain NPC Severity Score (ex-US)	Ambulation, Fine Motor, Speech, Swallow, Cognition	End of Study at Week 96
Secondary	Change in ataxia as measured by Spinocerebellar ataxia functional index	SCAFI	Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192
Secondary	Change in adaptive behavior as measured by Vineland Adaptive Behavior Scale II	Vineland Adaptive Behavior Scale II	Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192
Secondary	Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale	PAS	Change from Baseline measured at Interim Analysis Week 48
Secondary	Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale	PAS	Change from Baseline measured at End of Study Week 96