Phase 3 Study to Evaluate Intravenous Trappsol(R) Cyclo(TM) in Pediatric and Adult Patients With Niemann-Pick Disease Type C1 (TransportNPC)
Niemann-Pick Disease, Type C1
About this trial
This is an interventional treatment trial for Niemann-Pick Disease, Type C1 focused on measuring NPC1, cyclodextrin, Niemann-Pick, Niemann-Pick Type C, NPC, Niemann Pick C, Niemann Pick Type C, Niemann Pick
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of NPC1
- Annual Severity Increment Score between 0.5 and 2.0 using the 17-domain NPC Severity Scale
- 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).
- Body weight greater than 4.5 kg and less than or equal to 125 kg
- Presenting at least 1 neurological symptom of the disease
- Written informed consent
- Willing and capable to participate in all aspects of trial design
- Ability to travel to the trial site at scheduled times
- Contraception requirements per protocol
- Caregiver consent as appropriate to participate in all protocol-specified assessments for duration of trial
- 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
- 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:
- Recipient of a liver transplant within <12 months or planned liver transplantation
- Patients with active liver disease from any cause other than NPC1
- Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or international normalized ratio > 1.8
- Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate <60ml/min/1.73m2.
- Use of curcumin or fish oil within 12 weeks prior to enrollment
- Known or suspected allergy or intolerance to the study treatment
- In the opinion of the Investigator, the patient's clinical condition does not allow for the blood collection required as per protocol specific procedures.
- 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
- Treatment with any other investigational drug during the study
- Pregnancy or breastfeeding
- 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)
- 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.
- Neurologically asymptomatic patients
- Inability to participate in the primary study assessment (4D-NPC-SS or 5D-NPC-SS) as determined by the Investigator
- 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
Sites / Locations
- UCSF Benioff Children's Hospital OaklandRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- UPMC Children's HospitalRecruiting
- Lysosomal and Rare Disorders Research & Treatment Center, Inc.Recruiting
- Melbourne Children's Trials Centre Murdoch Children's Research InstituteRecruiting
- Royal Melbourne HospitalRecruiting
- Metabolic Clinical Trials UnitRecruiting
- Hospital de Clínicas de Porto AlegreRecruiting
- SphinCS GmbHRecruiting
- Emek Medical Center-Department of PediatricsRecruiting
- Soroka Medical CenterRecruiting
- Istituto Neurologico Carlo BestaRecruiting
- Szpital Uniwersytecki w KrakowieRecruiting
- Hospital Sant Joan de Déu - Neurology DepartmentRecruiting
- Hospital Universitari de BellvitgeRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- National Taiwan University HospitalRecruiting
- Gazi University Faculty of MedicineRecruiting
- Ege University Medical School, Department of Inborn Errors of MetabolismRecruiting
- Birmingham Children's Hospital NHS Foundation Trust · Department of Inherited Metabolic Disorders ServiceRecruiting
- Salford Royal Foundation NHS TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Placebo Comparator
Experimental
Experimental
Placebo comparator
Open Label sub-study for Infants up to age 3
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
Intravenous administration of 0.5N saline over at least 6.5 hours every 2 weeks
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.