VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease

Key Inclusion Criteria:

Parts A/B:

1. Had onset of neurological symptoms prior to 15 years of age
2. Has confirmed diagnosis of NPC1 determined by either:

1. two NPC1 mutations
2. positive filipin staining and at least one NPC1 mutation
3. vertical supranuclear gaze palsy (VSNGP) in combination with either: one NPC1 mutation, OR positive filipin staining or oxysterol levels consistent with NPC disease and no Niemann-Pick Type C2 (NPC2) Disease mutations
3. Adult participant or parent/guardian has provided written informed consent, with assent collected from minors of appropriate age
4. Is able to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia
5. Has an NPC Clinical Severity Scale Score of 1 through 4, inclusive, in two or more of the following components: ambulation, fine motor skills, or swallowing; and has a score of 0 through 4 on the cognition component
6. Has a total NPC Clinical Severity Scale Score of 10 or greater
7. If taking miglustat, must have been on a stable dose for past 6-8 weeks and be willing to remain on a stable dose
8. If participant has seizures, they have been adequately controlled for 3 months without changing dose or regimen
9. Has agreed to discontinue all non-prescription supplements at least 1 month prior to first dose (Study Day 0)
10. Has agreed to discontinue any other investigational treatments for NPC including vorinostat or arimoclomol at least 3 months prior to first dose (Study Day 0)
11. If of child-bearing potential (not surgically sterile), agrees to use a medically acceptable method continuously, until at least 30 days after participation in the study

Key Exclusion Criteria:

1. Has exclusion criteria as assessed by NPC Clinical Severity Scale:

1. Unable to walk, wheelchair dependent (ambulation NPC score=5)
2. Has need for a nasogastric tube to overcome swallowing difficulties (swallowing NPC score=5) unless used for supplemental feeding or administering medication
3. severe dysmetria (fine motor score =5) or
4. minimal cognitive function (cognition NPC score=5)
2. Weighs less than 15 kg
3. Has had prior treatment with intravenous 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for NPC1 disease, unless the subject has undergone a minimum 3-month washout period prior to Study Day 0, or has had any prior intrathecal (IT) administration of HP-β-CD
4. Is taking antipsychotics for treatment of psychosis; use of antipsychotic medication for treatment of other disorders (e.g., Attention Deficit Hyperactivity Disorder) will not exclude participation in this trial
5. Has a history of hypersensitivity reactions to any product containing HP-β-CD
6. Has a spinal deformity that could impact the ability to perform a lumbar puncture
7. Has had a skin infection in the lumbar region within 2 months of study entry
8. Has neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10\^9/L
9. Has thrombocytopenia (platelet count of less than 75 X 10\^9/L)
10. Has activated partial thromboplastin time (aPTT) or prothrombin time (PT) prolonged by \> 1.5 times the upper limit of normal (ULN) or known history of a bleeding disorder
11. Has had status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified
12. Has evidence of either obstructive hydrocephalus or normal pressure hydrocephalus
13. Has recently used anticoagulants \[in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety\].
14. Is unable to comply with the study procedures or has a clinical disease or laboratory abnormality that in the opinion of the investigator would potentially increase the risk of participation

For more information on this trial, visit clinicaltrials.gov.