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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04860960




Registration number
NCT04860960
Ethics application status
Date submitted
15/04/2021
Date registered
27/04/2021
Date last updated
4/06/2024

Titles & IDs
Public title
Phase 3 Study to Evaluate Intravenous Trappsol(R) Cyclo(TM) in Pediatric and Adult Patients With Niemann-Pick Disease Type C1
Scientific 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)
Secondary ID [1] 0 0
CTD-TCNPC-301
Universal Trial Number (UTN)
Trial acronym
TransportNPC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Niemann-Pick Disease, Type C1 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Dementias
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Hydroxypropyl-beta-cyclodextrin
Treatment: Drugs - Placebo

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

Placebo Comparator: Placebo comparator - Intravenous administration of 0.5N saline over at least 6.5 hours every 2 weeks

Experimental: 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.


Treatment: Drugs: Hydroxypropyl-beta-cyclodextrin
Dose is 2000 mg/kg body weight provided every 2 weeks intravenously

Treatment: Drugs: Placebo
0.5N saline provided every 2 weeks intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in 4-Domain NPC Severity Score (US only)
Timepoint [1] 0 0
Interim Analysis at Week 48
Primary outcome [2] 0 0
Change from Baseline in 4-Domain NPC Severity Score (US only)
Timepoint [2] 0 0
End of Study at Week 96
Primary outcome [3] 0 0
Change from Baseline in 5-Domain NPC Severity Score (ex-US)
Timepoint [3] 0 0
Interim Analysis at Week 48
Primary outcome [4] 0 0
Change from Baseline in 5-Domain NPC Severity Score (ex-US)
Timepoint [4] 0 0
End of Study at Week 96
Secondary outcome [1] 0 0
Change in ataxia as measured by Spinocerebellar ataxia functional index
Timepoint [1] 0 0
Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192
Secondary outcome [2] 0 0
Change in adaptive behavior as measured by Vineland Adaptive Behavior Scale II
Timepoint [2] 0 0
Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192
Secondary outcome [3] 0 0
Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale
Timepoint [3] 0 0
Change from Baseline measured at Interim Analysis Week 48
Secondary outcome [4] 0 0
Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale
Timepoint [4] 0 0
Change from Baseline measured at End of Study Week 96

Eligibility
Key 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.
Minimum age
3 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
Accrual to date
Final
94
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Melbourne Children's Trials Centre Murdoch Children's Research Institute - Parkville
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [3] 0 0
Metabolic Clinical Trials Unit - Adelaide
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
Córdoba
Country [10] 0 0
Brazil
State/province [10] 0 0
Porto Alegre
Country [11] 0 0
Brazil
State/province [11] 0 0
São Paulo
Country [12] 0 0
Germany
State/province [12] 0 0
Hochheim
Country [13] 0 0
Germany
State/province [13] 0 0
Münster
Country [14] 0 0
Israel
State/province [14] 0 0
Afula
Country [15] 0 0
Israel
State/province [15] 0 0
Be'er Sheva
Country [16] 0 0
Italy
State/province [16] 0 0
Catania
Country [17] 0 0
Italy
State/province [17] 0 0
Milan
Country [18] 0 0
Italy
State/province [18] 0 0
Padova
Country [19] 0 0
Italy
State/province [19] 0 0
Udine
Country [20] 0 0
Poland
State/province [20] 0 0
Kraków
Country [21] 0 0
Poland
State/province [21] 0 0
Warsaw
Country [22] 0 0
Saudi Arabia
State/province [22] 0 0
Riyadh
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Taiwan
State/province [25] 0 0
Taipei
Country [26] 0 0
Turkey
State/province [26] 0 0
Ankara
Country [27] 0 0
Turkey
State/province [27] 0 0
Izmir
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Birmingham
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cyclo Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04860960
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Karen Mullen, MD
Address 0 0
Cyclo Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries