Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C

Inclusion Criteria

• Age 0 to 6 months of age at time of enrollment, both genders, and any race/ethnicity.
• Diagnosis of NPC (either NPC1 or NPC2) based upon meeting any of the two following conditions:

A. Two variants classified as pathogenic or likely pathogenic in NPC1/NPC2 on clinical laboratory testing, or B. One variant classified as pathogenic or likely pathogenic on clinical laboratory testing and a positive NPC biochemical marker (oxysterol or bile acid biomarker or PPCS/Lyso509) test, if acid sphingomyelinase deficiency and cholesterol ester storage disease have been excluded either by clinical molecular testing of the SMPD1 and LIPA genes or by clinical biochemical assay for acid sphingomyelinase and lysosomal acid lipase enzymes (or a combination of enzymatic and molecular testing).

Variants will be interpreted using the American College of Medical Genetics guidelines for the interpretation of sequence variants (2015) and testing must be performed by a CLIA-certified laboratory.

• Subjects with evidence of NPC-related liver disease as defined by direct bilirubin (DB) >2mg/dL or DB/total bilirubin ratio >0.2.
• Ability to travel to a research site.
• Willing to participate in all aspects of trial design including serial blood collections.
• Parent / guardian must provide written informed consent to participate in the study. Because of the age range intended for inclusion, assent will not possible.

Exclusion Criteria

• Age > 6 months at time of enrollment in the trial.
• A medical condition (such as clinically significant bleeding diathesis or evidence of immune suppression) that in the opinion of the investigator precludes placement of an intravenous catheter
• An absolute neutrophil count (ANC) of less than 1,500 per microliter.
• A platelet count less than 75, 000 per microliter.
• History of severe neonatal encephalopathy, per modified Sarnat including level of consciousness as stupor/coma, absent spontaneous activity, decerebrate posture, flaccid tone, absent suck, absent moro, diverted/nonreactive pupils, lack of heart rate variability, apnea.
• Subjects, who in the opinion of the investigators, are unable to comply with the protocol or have specific health concerns that would potentially increase the risk of participation. Examples of inability to comply include unwillingness to relocate or travel to a study site, suspected noncompliance with study procedures, behavior that jeopardizes the safety or security of the data or study staff, and other causes of inability to comply.
• Concurrent participation in another investigational drug trial.
• History of renal disease or evidence of acute kidney injury defined as serum creatinine greater than 1.5 mg/dL or an increase of at least 0.2-0.3 mg/dL per day.