IV VTS-270 for Niemann-Pick Disease

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for Niemann-Pick disease type C (NPC), a rare genetic disorder affecting the liver and brain, often with early-life symptoms. The study examines whether the drug adrabetadex (VTS-270), administered through an IV, can treat liver disease in infants with NPC1. Infants diagnosed with NPC and related liver issues may participate. Participants must travel to the research site and engage in all study activities, including blood tests. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that adrabetadex (VTS-270) can slow the progression of Niemann-Pick Type C1 (NPC1) disease. Importantly, studies suggest this treatment is generally safe. Side effects can occur, depending on the administration method and dosage. Reported issues include hearing problems and increased liver enzymes, but overall, the safety profile is considered acceptable.

In earlier studies, patients received adrabetadex in various ways, such as directly into the spinal canal, which helped slow the disease. For this trial, the drug is administered intravenously (IV). The safety of adrabetadex has been studied in different forms, and while some side effects have been noted, they are generally manageable.

These findings suggest that while there are some risks, adrabetadex may be safe for treating NPC1, especially with careful monitoring. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Niemann-Pick disease?

Unlike the standard treatments for Niemann-Pick Disease, which often focus on managing symptoms, IV VTS-270 uses 2-Hydroxypropyl-Beta-Cyclodextrin to target the underlying issue of cholesterol buildup in cells. This treatment is administered intravenously, allowing it to reach affected areas more efficiently compared to oral medications. Researchers are particularly excited about its potential to not only slow disease progression but also improve neurological symptoms, offering a more comprehensive approach to patient care.

What evidence suggests that this treatment might be an effective treatment for Niemann-Pick disease?

Research has shown that adrabetadex (VTS-270), which participants in this trial may receive, may help treat Niemann-Pick Disease Type C1 (NPC1), especially in babies. Studies have found that this treatment can improve liver problems and was safe in past trials with infants. In animal studies, it reduced disease symptoms and increased lifespan. Human studies also suggest it benefits brain-related symptoms of NPC1. Additionally, research indicates that people treated with adrabetadex tend to live longer. These findings suggest that VTS-270 might effectively manage issues related to NPC1. ^{5 6 7 8 9}

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02534844

VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease This study is to find out how safe and effective VTS-270 is for patients with Niemann-Pick Type C1 (NPC1) disease who have neurologic symptoms.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8170172/

A phase 1/2 open label nonrandomized clinical trial of ... Intravenous 2HPBCD was tolerated in three infants with liver disease due to NPC. Keywords: Niemann Pick C; Clinical trial; 2-hydroxypropyl-β- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04958642

Adrabetadex to Treat Niemann-Pick Type C1 (NPC1) ... This study is to evaluate how safe and effective adrabetadex is for participants with Niemann-Pick Type C1 (NPC1) disease who experience neurologic symptoms ( ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S038776042400041X

Long-term efficacy of intrathecal cyclodextrin in patients ... Long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, patients still experience some disease progression.

5. biospace.com biospace.com/press-releases/data-analyses-show-benefit-for-individuals-with-infantile-onset-niemann-pick-disease-type-c-treated-with-investigational-drug-adrabetadex

Data Analyses Show Benefit for Individuals With Infantile ... Analysis shows statistically significant survival benefit in individuals with infantile-onset Niemann-Pick disease type C (NPC) treated with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28803710/

a non-randomised, open-label, phase 1-2 trial - PubMed - NIH Patients with NPC1 treated with intrathecal HPβCD had slowed disease progression with an acceptable safety profile.

7. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Hydroxypropyl-%CE%B2-cyclodextrin.pdf

Hydroxypropyl-β-cyclodextrin HPβCD slows disease progression in Niemann-Pick disease Type C1. Adverse events depend on route, dose, and dosing regimen, but ototoxicity and increased liver ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01747135

Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type ... Researchers want to test if it is safe to use HPBCD for NPC1. They want to see if it can help brain cells process cholesterol better.

9. sciencedirect.com sciencedirect.com/science/article/pii/S109671922200419X

Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® ... Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and ...