HYDROXYPROPYLBETADEX for Niemann-Pick disease type C1

Inclusion criteria

• {"criterion_text":"- Patients ≥3 years of age at Screening."}
• {"criterion_text":"- 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 evaluated by the Investigator in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient"}
• {"criterion_text":"- The patient or legally authorized representative has read and signed the informed consent (or assent, as applicable) form prior to any study-related procedures"}
• {"criterion_text":"- The legally authorized representative (if applicable) agrees for the patient to participate in all aspects of the study"}
• {"criterion_text":"- The patient’s caregiver (as applicable) agrees to participate in all of the protocol-specified assessment scales, questionnaires, and interviews for the duration of the trial"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Body weight >4.5 kg to ≤125 kg"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients who have previously been treated with hydroxypropyl-β- cyclodextrin (HPβCD) 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 HPβCD."}
• {"criterion_text":"- Ability to travel to the corresponding clinical study site at the scheduled visit times for evaluation and follow-up."}

Exclusion criteria

• {"criterion_text":"- Recipient of a liver transplant within <12 months or planned liver transplantation. Patients who have received a successful transplant over 12 months or longer ago can be screened."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Neurologically asymptomatic patients"}
• {"criterion_text":"- Inability to participate in the primary study assessment (4D-NPC-SS and 5D-NPC-SS) as determined by the Investigator."}
• {"criterion_text":"- Patients with active liver disease from any cause other than NPC1 or prolonged icterus or malformation of organs other than NPC1"}
• {"criterion_text":"- Clinical evidence of acute liver disease including associated symptoms of jaundice or right upper quadrant pain or international normalized ratio >1.8"}
• {"criterion_text":"- Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. In patients aged ≤18 years, eGFR is calculated according to the Schwartz equation (Schwartz and Work, 2009), and in patients aged >18 years eGFR is calculated using the Modification of Diet in Renal Disease equation"}
• {"criterion_text":"- Use of curcumin or fish oil supplements within 12 weeks prior to enrollment"}
• {"criterion_text":"- Known or suspected allergy or intolerance to the study treatment"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Treatment with any other investigational drug during the study"}
• {"criterion_text":"- Pregnancy or breastfeeding"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured as mean change in the 5D-NPC-SS composite score (domains: Ambulation, Fine Motor, Speech, Swallow, Cognition) from Baseline (Week 0) to 48 weeks (interim analysis) as submitted as primary to EU and RoW."}
• {"endpoint_text":"- The primary endpoints as measured in study patients, regardless of region and country, but submitted as primary to the EU and RoW are:• 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","definition_or_measurement_approach":"Measured as mean change in the 5D-NPC-SS composite score from Baseline (Week 0) to 96 weeks (final analysis) as submitted as primary to EU and RoW."}
• {"endpoint_text":"- The primary endpoints as measured in all study patients, regardless of country, but submitted as primary to US are: • Interim Analysis: Mean change in the 4D-NPC-SS (Ambulation, Fine Motor, Speech, and Swallow) composite score from Baseline (Week 0) to 48 weeks","definition_or_measurement_approach":"Measured as mean change in the 4D-NPC-SS composite score (domains: Ambulation, Fine Motor, Speech, Swallow) from Baseline (Week 0) to 48 weeks (interim) as submitted as primary to US."}
• {"endpoint_text":"- The primary endpoints as measured in all study patients, regardless of country, but submitted as primary to US are:• Final Analysis: Mean change in the 4D-NPC-SS (Ambulation, Fine Motor, Speech, and Swallow) composite score from Baseline (Week 0) to 96 weeks","definition_or_measurement_approach":"Measured as mean change in the 4D-NPC-SS composite score from Baseline (Week 0) to 96 weeks (final) as submitted as primary to US."}

Secondary endpoints

• {"endpoint_text":"- Mean change from Baseline in the SCAFI at 48 and 96 weeks","definition_or_measurement_approach":"Measured as mean change from Baseline in the Spinocerebellar Ataxia Functional Index (SCAFI) at 48 and 96 weeks."}
• {"endpoint_text":"- Mean change from Baseline in the Vineland-2 composite raw score, including the optional Motor Skills domain, at 48 and 96 weeks","definition_or_measurement_approach":"Measured as mean change from Baseline in the Vineland Adaptive Behavior Scale, 2nd edition (composite raw score, optionally including Motor Skills) at 48 and 96 weeks."}
• {"endpoint_text":"- Mean change from Baseline in the patient’s ability to swallow as assessed by the PAS, at 48 and 96 weeks (at select sites)","definition_or_measurement_approach":"Measured as mean change from Baseline in swallowing ability using the Penetration-Aspiration Scale (PAS) at 48 and 96 weeks (assessed at select sites)."}

Poland

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

19-08-2025

Processing Time Days

301

Number Of Sites

2

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

19-08-2025

Processing Time Days

301

Number Of Sites

3

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

28-11-2025

Processing Time Days

402

Number Of Sites

2

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

503

Number Of Sites

2

Number Of Participants

12

Primary sponsor

Full Name

Cyclo Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials Holdings Inc.

Responsibilities

Sponsor/contract research organization duties (sponsorDuties codes: 1,10,11,12,2,5,6,7,8,9); contact email: olu.daramola@worldwide.com; phone: +16106328190

Third parties

• {"country":"United States","full_name":"Worldwide Clinical Trials Holdings Inc.","duties_or_roles":"sponsorDuties codes: 1,10,11,12,2,5,6,7,8,9","organisation_type":"Pharmaceutical company"}