safety and tolerability study of vts-270 in pediatric participants with niemann-pick type c (npc) disease

Conditions: Niemann-Pick Disease, Type C

Summary: this is a phase-2, multicenter, multiple dose, open-label, 2-part evaluation study which will primarily assess the safety and tolerability of vts-270 (2-hydroxypropyl beta-cyclodextrin \[hp-β-cd\]) in pediatric participants with age \<4 years.

in part a of the study, participants after confirmation of the diagnosis of npc will receive vts-270 for 20 weeks during the active treatment period. further, based on investigator's discretion participants would either end treatment with a follow-up visit 28 days (+/- 7) days after last treatment, or will enter to part-b to benefit from open-label treatment.

Eligibility criteria:
inclusion criteria: 1. the parent(s)/legal guardian(s) must be adequately informed and understand the nature and risks of the study. the participant's parent or legal guardian must provide a signature and date on the informed consent form (icf). 2. participants must have neurologial symptoms defined as, any area of developmental delay 1 sd below the mean (example, developmental quotient or standard score under 85 in any domain on the mullen scale early learning \[msel\]) or a significant developmental quotient /standard score drop on the msel. 3. diagnosis of npc determined by one of the following: 1. two npc1 or npc2 mutations; 2. positive filipin staining or oxysterol testing and at least one npc1 or npc2 mutation; 3. vertical supranuclear gaze palsy in combination with either: i. one npc1/npc2 mutation, or ii. positive filipin staining or oxysterol levels consistent with npc1 or npc2 disease. 4. if taking miglustat (zavesca), participant(s) must have been on a stable dose for 6 weeks prior to the screening visit and willing to remain on a stable dose for the duration of participation in this study. if not taking migulstat, the participant must have been off treatment for a minimum of 6 weeks prior to the baseline visit. 5. if a participant has a history of seizures, the condition must be adequately controlled (the pattern of seizure activity must be stable) and the participant must be on a stable dose and regimen of antiepileptic medication(s) 4 weeks prior to the screening visit. 6. prior exposure to vts-270 is permitted. 7. the participant's parent(s)/legal guardian(s) are able to communicate effectively with study personnel. 8. parent(s)/legal guardian(s) are able and willing to follow all protocol requirements and study restrictions. 9. parent(s)/legal guardian(s) are able and willing to return participants for all study visits. exclusion criteria: 1. is from a vulnerable population, as defined by the us cfr title 45, part 46, section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the institutional review board (irb)/independent ethics committee (iec). 2. has a history of sensitivity or allergy to any product containing hp-β-cd. 3. a history of hypersensitivity reactions or allergy to the anesthetic and/or sedative agents to be used for the lumbar puncture procedure. 4. taken an anticoagulant in the 2 weeks prior to the baseline visit or plan to use anticoagulants during the study. 5. change in antiepileptic treatment between the screening visit and the baseline visit. 6. received treatment for any investigational product (exclusive of vts-270) within 4 weeks of the baseline visit or at least 5 half-lives, whichever criteria is longest. 7. a suspected infection of the central nervous system or any systemic infection. 8. a spinal deformity that is likely to impact the ability to perform repeated lps. 9. evidence of obstructive hydrocephalus or normal pressure hydrocephalus. 10. undergoing intravenous treatment with vts-270. note: prior or current treatment with it vts-270 is not exclusionary. 11. a known bleeding disorder. 12. has any of the following laboratory abnormalities ( greater than 1.5 times the upper limit of normal) at the screening visit: * neutropenia * thrombocytopenia * activated partial thromboplastin time * prothrombin time prolongation. 13. has any other clinically significant disease, disorder or laboratory abnormality, which, in the opinion of the investigator, might put the participant at risk due to participation in the study, or may influence the results of the study or the participant's ability to complete the study. 14. is participating in or plans to participate in any other interventional research study from the time of screening and throughout this study. 15. also excluded are participant, who in the opinion of the investigator, are unable to comply with the protocol or who have a medical condition (eg, cardiovascular, respiratory, hematologic, neurologic, psychiatric, renal) that would potentially increase the risk of study participation.