IV VTS-270 for Niemann-Pick Disease

Recruiting in Palo Alto (17 mi)

Overseen byPatricia I Dickson, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Washington University School of Medicine

No Placebo Group

Trial Summary

What is the purpose of this trial?Niemann-Pick disease, type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. NPC results from mutation of either the Niemann-Pick C1 disease (NPC1) (\~95% of cases) or NPC2 genes. NPC is characterized by the endolysosomal storage of unesterified cholesterol and lipids in both the central nervous system and peripheral tissues such as the liver. Individuals with NPC demonstrate progressive central nervous system decline including inability to coordinate balance, gait, extremity and eye movements. Acute liver disease in the newborn/infant period is frequently observed, but subsequently resolves. However, chronic, sub-clinical liver disease persists. Intrathecal 2-Hydroxypropyl-β-Cyclodextrin (HP-β-CD, VTS-270), also known as adrabetadex, has proven effective in reducing the signs and prolonging life in animal models and Phase 1/2a data support efficacy in NPC1 patients. Adrabetadex (VTS-270) also has been shown to be effective in treating liver disease in the NPC1 cat. This Phase 1/2a, open-label, multiple ascending dose trial will evaluate whether adrabetadex (VTS-270) administered intravenously is effective in treating acute liver disease in NPC1 infants.

Eligibility Criteria

This trial is for infants aged 0-6 months with Niemann-Pick disease type C (NPC) and evidence of NPC-related liver disease. They must be able to travel for the study, undergo blood collections, and have parental consent. Infants with severe immune suppression, kidney injury, low neutrophil or platelet counts, or severe neonatal encephalopathy cannot participate.

Inclusion Criteria

My liver is affected by my condition, shown by high bilirubin levels.

I have been diagnosed with NPC based on genetic tests or a combination of genetic and biochemical tests.

Willing to participate in all aspects of trial design including serial blood collections.

+3 more

Exclusion Criteria

I am older than 6 months.

Your blood has fewer than 75,000 platelets per tiny drop.

I have kidney problems or my creatinine levels are high.

+5 more

Participant Groups

The trial tests adrabetadex (VTS-270), given intravenously to treat acute liver disease in infants with NPC1. It's an open-label Phase 1/2a study where all participants receive the drug in increasing doses to evaluate its effectiveness and safety.

1Treatment groups

Experimental Treatment

Group I: IV adrabetadex (VTS-270) for NPC1 infantsExperimental Treatment1 Intervention

Phase 1: Dosing frequency will be twice a week administered via a peripherally inserted central catheter (PICC) for six weeks for a total of 12 administrations. Doses 3-12 will occur as an outpatient. Doses to be studied are 500, and 1000 mg/kg. Six subjects will be studied at each dose level. Cohort 1: Subjects 1-6 will receive 500 mg/kg Cohort 2: Subjects 7-12 will receive 1000 mg/kg Subjects who demonstrate significant reduction either in the glycine-conjugated trihydroxycholanic acid biomarker or serum bilirubin (direct bilirubin or direct bilirubin:total bilirubin ratio) will be allowed to crossover into the second phase of the study, an open-label phase of six months duration. In the this phase of the study, dosing frequency will be monthly with IV VTS-270 administered via peripheral IV access for six months for a total of six administrations.