IV VTS-270 for Niemann-Pick Disease

Overseen By Barbara B Warner, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Disqualifiers: Age > 6 months, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 18

12 Participants Needed

What You Need to Know Before You Apply

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.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

Is IV VTS-270 (2-Hydroxypropyl-Beta-Cyclodextrin) safe for humans?

2-Hydroxypropyl-Beta-Cyclodextrin (HP-β-CD) has been used in clinical trials for Niemann-Pick Disease Type C and has shown some safety concerns. Some patients experienced adverse effects like hearing loss, fever, and chemical meningitis, but it generally has a low toxicity potential. More controlled trials are needed to fully understand its safety profile. ^{1 2 3 4 5}

How is the drug 2-Hydroxypropyl-Beta-Cyclodextrin unique for treating Niemann-Pick Disease?

2-Hydroxypropyl-Beta-Cyclodextrin (HPβCD) is unique because it is administered intravenously and works by restoring cholesterol balance in the body, including the brain, which is crucial for treating Niemann-Pick Disease Type C. Unlike other treatments, it directly impacts cholesterol metabolism in both peripheral tissues and the central nervous system, offering a novel approach to managing this rare disease. ^{1 4 5 6 7}

What data supports the effectiveness of the drug 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Disease?

Research shows that 2-Hydroxypropyl-Beta-Cyclodextrin (HP-β-CD) can help stabilize Niemann-Pick Disease Type C by improving cholesterol metabolism in the body and brain, leading to clinical benefits and slowing disease progression. In studies, patients showed improvements in clinical outcomes and brain activity, although some experienced side effects like hearing loss. ^{1 2 3 5 7}

Who Is on the Research Team?

Patricia I Dickson, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Infants receive IV adrabetadex (VTS-270) twice weekly for 6 weeks. Initial week in NICU with various procedures including blood draws, urine collection, and PICC line placement.

6 weeks

12 visits (in-person)

Treatment Phase 2

Open-label phase for subjects showing significant biomarker reduction. Monthly IV adrabetadex (VTS-270) administration for 6 months.

6 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 2-Hydroxypropyl-Beta-Cyclodextrin

Trial Overview 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.

How Is the Trial Designed?

Group I: IV adrabetadex (VTS-270) for NPC1 infants Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann-Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann-Pick C1. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® Cyclo™) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Linear Cyclodextrin Polymer Prodrugs as Novel Therapeutics for Niemann-Pick Type C1 Disorder. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Evaluation of 6-O-α-Maltosyl-β-Cyclodextrin as a Potential Therapeutic Agent Against Niemann-Pick Disease Type C. [2020]