Niemann Pick Disease Type C1 MedDRA version: 20.0 Level: PT Classification code 10029403 Term: Niemann-Pick disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Trappsol® Cyclo™
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
Other descriptive name: HYDROXYPROPYLBETADEX
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
Cyclo Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients =3 years of age at Screening. 2. Diagnosis of NPC1 confirmed by: a. Genetically confirmed (deoxyribonucleic acid sequence analysis) by mutations in both alleles of NPC1 OR b. Mutation in only 1 allele of NPC1 and either positive filipin staining in skin or vertical supranuclear gaze palsy (VSGP). 3. Patients with an ASIS between 0.5 to 2.0 (inclusive) at Screening using the 17 Domain Niemann-Pick Type C Severity Scale (17D-NPC-SS) composite score. For patients who remain incontinent due to inability to train to become continent, the relative contribution to the 17-D-NPC-CSS composite score can be adjusted per the Investigator's judgment as not applicable, following conferring with the Medical Monitor. A not applicable score will be scored as a "0" for this domain. 4.Treated or not treated with miglustat. a. If a patient is receiving treatment with miglustat, the dose must have been stable for at least 3 continuous months prior to the first Screening Visit. b. If a patient has been discontinued from prescribed treatment with miglustat, she/he must have been discontinued for at least 3 continuous months prior to the first Screening Visit. 5. Body weight >4.5 kg to =125 kg 6. Presenting at least 1 neurological symptom of the disease (including, but not limited to, hearing loss, VSGP, ataxia, dementia, dystonia, history of seizures, cataplexy, dysarthria, or dysphagia) 7. Willing and capable to participate in all aspects of study design, including blood sampling (efficacy, PK, blood biomarkers, and safety laboratory tests). Adequate compliance with the assessments to obtain complete data can become a discussion between the Investigator and the medical monitor prior to randomization at the Baseline Visit the Medical Monitor prior to randomization at the Baseline Visit. 8.Patients who have previously been treated with hydroxypropyl-ß- cyclodextrin (HPßCD) are eligible for participation in the study if their last intrathecal administration was 3 months or longer ago or if their last IV administration was 6 months or longer ago. No more than approximately 10% of the total number of randomized patients can previously have been exposed to HPßCD. 9. Ability to travel to the corresponding clinical study site at the scheduled visit times for evaluation and follow-up 10. Contraception requirements: a. All sexually active WOCBP (post menarche) must use highly effective contraception during the study and until 3 months after the last dose of study treatment b. Highly effective birth control methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; or vasectomized partner c. All sexually active male patients with WOCBP partners (post menarche) must use a condom with or without spermicide in addition to the birth control used by their partners during the study and until 3 months after the last dose of study treatment d. Sexual abstinence is considered a highly effective birth control method only if it is defined as refraining from heterosexual intercourse during the study and for 3 months after the last dose of study treatment for WOCBP and for male patients with WOCBP partners. The reliability of sexual abstinence needs to be evaluat
Exclusion criteria
Exclusion criteria: 1. Recipient of a liver transplant within 1.8 4. Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate (eGFR) 18 years eGFR is calculated using the Modification of Diet in Renal Disease equation 5. Use of curcumin or fish oil supplements within 12 weeks prior to enrollment 6. Known or suspected allergy or intolerance to the study treatment 7. 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. Please consult with the Medical Monitor on a case-by-case basis. 8. Treatment with any other investigational drug during the study 9. Pregnancy or breastfeeding 10. Current participation in another study 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) 11. 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). This includes patients with ongoing seizures that are not stable in frequency or type or duration over a 2-month period prior to enrollment, requiring change in dose of antiepileptic medication (other than adjustment for weight) over a 2-month period prior to enrollment, or requiring 3 or more antiepileptic medications to control seizures over a 2-month period prior to enrollment 12. Neurologically asymptomatic patients 13. Inability to participate in the primary study assessment (4D-NPC-SS and 5D-NPC-SS) as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study has dual primary objectives, such that the primary objective is to evaluate the effectiveness of Trappsol Cyclo and standard of care (SOC) compared to placebo and SOC as measured by an improvement in the 4-domain (4D-NPC-SS) or 5-domain (5D-NPC-SS) Niemann-Pick disease Type C Severity Scale: •The 4D-NPC-SS will be utilized as the primary objective for the US. •The 5D-NPC-SS will be utilized as an exploratory objective for the US. •The 5D-NPC-SS will be utilized as the primary objective for the EU and RoW. •The 4D-NPC-SS will be utilized as an exploratory objective for the EU and RoW. All randomized patients, regardless of country, will be assessed by both the 4D-NPC-SS and the 5D-NPC-SS assessment tools per the Schedule of Assessments (SoA). ;Secondary Objective: •To determine the ability of Trappsol Cyclo and SOC compared to placebo and SOC to improve ataxia as assessed by the Spinocerebellar Ataxia Functional Index (SCAFI) •To evaluate the effectiveness of Trappsol Cyclo and SOC compared to placebo and SOC as assessed by the Vineland Adaptive Behavior Scale 2nd edition (Vineland 2) composite raw score, including the optional Motor Skills domain •To evaluate the effectiveness of Trappsol Cyclo and SOC compared to placebo and SOC with regards to the patient’s ability to swallow as assessed by the Penetration Aspiration Scale (PAS) ;Primary end point(s): The primary endpoints as measured in study patients, regardless of region and country, but submitted as primary to the EU and RoW are: • Interim Analysis: Mean change in the 5D NPC SS composite score (Ambulation, Fine Motor, Speech, Swallow, and Cognition) from Baseline (Week 0) to 48 weeks •Final Analysis: Mean change in the 5D NPC SS composite score (Ambulation, Fine Motor, Speech, Swallow, and Cognition) from Baseline (Week 0) to 96 weeks The primary endpoints as measured in all study patients, regardless of country, but submitted as primary to US are: • Interim Analysis: Mean change | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mean change from Baseline in the SCAFI at 48 and 96 weeks • Mean change from Baseline in the Vineland 2 composite raw score, including the optional Motor Skills domain, at 48 and 96 weeks • Mean change from Baseline in the patient’s ability to swallow as assessed by the PAS, at 48 and 96 weeks (at select sites) ;Timepoint(s) of evaluation of this end point: 48 and 96 weeks | — |
Countries
Argentina, Australia, Brazil, France, Germany, Israel, Italy, Poland, Saudi Arabia, Spain, Taiwan, Türkiye, Ukraine, United Kingdom, United States
Contacts
Public ContactChief Medical Officer
Boyds
Outcome results
None listed