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

NCT03471143 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2017081145U01HD090845-04
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Niemann-Pick Disease, Type C

Outcome Measures

Primary Outcomes (1)

• Efficacy of Adrabetadex (VTS-270) to Reduce Plasma Levels of a Conjugated Bile Acid, Known as 5α-cholanic Acid-3β, 5α, 6β-triol N-(Carboxymethyl)-Amide

  This bile acid, 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide, is elevated \>99% of NPC1 subjects, is largely generated in the liver and therefore provides a biochemical measure of oxidizable lysosomal unesterified cholesterol in liver tissue. The primary outcome measure in phase 1 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from baseline to 6 weeks. The primary outcome measure in phase 2 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from 6 weeks to the end of the 6 month treatment period.

  Phase 1: 6 weeks; Phase 2: 6 months

Secondary Outcomes (2)

• Effect of Drug on Serum Transaminases

  Phase 1: 6 weeks; Phase 2: 6 months

• Reduction of Liver and/or Spleen Volumes

  Phase 1: 6 weeks; Phase 2: 6 months

Study Arms (1)

IV adrabetadex (VTS-270) for NPC1 infants

EXPERIMENTAL

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.

Drug: VTS-270

Interventions

VTS-270 DRUG

VTS-270 (2-Hydroxypropyl-Beta-Cyclodextrin) will be administered intravenously to specifically target liver disease. In the first phase of the study, dosing frequency will be twice a week with IV adrabetadex (VTS-270) for six weeks for a total of 12 administrations. Subjects will be evaluated at each study visit for evidence of adverse effects. Doses to be studied are 500, and 1000 mg/kg. Six subjects will be studied at each dose level. Cohort 1: Subjects 1-6, 500 mg/kg Cohort 2: Subjects 7-12, 1000 mg/kg

Also known as: adrabetadex

IV adrabetadex (VTS-270) for NPC1 infants

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Ory DS, Ottinger EA, Farhat NY, King KA, Jiang X, Weissfeld L, Berry-Kravis E, Davidson CD, Bianconi S, Keener LA, Rao R, Soldatos A, Sidhu R, Walters KA, Xu X, Thurm A, Solomon B, Pavan WJ, Machielse BN, Kao M, Silber SA, McKew JC, Brewer CC, Vite CH, Walkley SU, Austin CP, Porter FD. Intrathecal 2-hydroxypropyl-beta-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial. Lancet. 2017 Oct 14;390(10104):1758-1768. doi: 10.1016/S0140-6736(17)31465-4. Epub 2017 Aug 10.

  PMID: 28803710 BACKGROUND

MeSH Terms

Conditions

Niemann-Pick Disease, Type C

Interventions

2-Hydroxypropyl-beta-cyclodextrin

Condition Hierarchy (Ancestors)

Niemann-Pick Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

beta-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Results Point of Contact

• Title: Dr. Patricia Dickson
• Organization: Washington University School of Medicine

pdickson@wustl.edu

314-273-2943

Study Officials

• Patricia I Dickson, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1/2a, open-label, dose escalation, multi-center study of adrabetadex (VTS-270) in subjects with NPC dosed twice a week with IV adrabetadex (VTS-270) for six weeks for a total of 12 administrations, followed by a six month open-label extension phase in which the subjects are dosed monthly with IV adrabetadex (VTS-270) for six months for a total of six administrations

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 20, 2018
• Study Start: February 22, 2019
• Primary Completion: October 4, 2024
• Study Completion: October 4, 2024
• Last Updated: January 5, 2026
• Results First Posted: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)