What side effects are associated with this type of intervention?

Common side effects of treatments for Niemann-Pick Disease, particularly those involving cholesterol solubilizing and mobilizing agents like Trappsol Cyclo (hydroxypropyl betacyclodextrin), include infusion-related reactions such as fever, chills, and headaches. Gastrointestinal symptoms like nausea and vomiting are also common. Long-term use may lead to liver and kidney function abnormalities, necessitating careful monitoring.

What prior FDA approvals exist?

The FDA has approved several treatments for Niemann-Pick Disease, particularly for type C1, which involves cholesterol accumulation. One notable treatment is miglustat (Zavesca), which inhibits the synthesis of glycosphingolipids and has shown efficacy in slowing neurological progression. Another investigational treatment similar to Trappsol Cyclo is VTS-270 (2-hydroxypropyl-beta-cyclodextrin), which also aims to solubilize and mobilize cholesterol. These treatments focus on managing the lipid storage abnormalities characteristic of Niemann-Pick Disease.

What other types of research exist?

Promising novel alternatives to Trappsol Cyclo for Niemann-Pick Disease Type C1 include: 1) Arimoclomol, a heat shock protein amplifier that has shown potential in clinical trials for NPC1. 2) VTS-270 (2-hydroxypropyl-beta-cyclodextrin), another cyclodextrin-based therapy with ongoing research. 3) Gene therapy approaches targeting the NPC1 gene to correct the underlying genetic defect. 4) Miglustat, an iminosugar that inhibits glycosphingolipid synthesis and has been used off-label for NPC1. These alternatives are in various stages of research and clinical trials, offering potential new avenues for treatment.

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Cyclodextrin

Trappsol Cyclo for Niemann-Pick Disease (TransportNPC Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Niemann-Pick Disease, particularly type C1, include miglustat and hydroxypropyl betacyclodextrin (such as Trappsol Cyclo). Miglustat works by inhibiting the synthesis of glycosphingolipids, which reduces the accumulation of these lipids in cells. Hydroxypropyl betacyclodextrin solubilizes and mobilizes cholesterol, facilitating its removal from lysosomes where it accumulates due to the defective NPC1 protein. These mechanisms are crucial for Niemann-Pick Disease patients as they directly target the storage of lipids and cholesterol, which is the primary cause of cellular dysfunction and the progressive neurological decline seen in the disease.

Phase 3

Waitlist Available

Research Sponsored by Cyclo Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Body weight greater than 4.5 kg and less than or equal to 125 kg

Ability to travel to the trial site at scheduled times

Must not have

Patients with uncontrolled, severe epileptic seizure periods (at least 3 consecutive severe epileptic seizures that required medication) within 2 months prior to completion of informed consent or assent, as applicable

Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate <60ml/min/1.73m2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192

Awards & highlights

Pivotal Trial

Summary

This trial is testing a medicine called Trappsol Cyclo, given through an IV, for patients with Niemann Pick disease type C1. The medicine helps remove harmful fat buildup in cells. The study will also look at safety in younger children. Trappsol Cyclo has shown promising results by mobilizing cholesterol, extending life, and reducing neurological damage in Niemann-Pick disease type C1.

Who is the study for?

This trial is for pediatric and adult patients with Niemann-Pick Disease Type C1. Participants must have a confirmed diagnosis, be able to follow the study's procedures, and weigh between 4.5 kg and 125 kg. They should not have severe kidney disease, recent liver transplant or active liver disease unrelated to NPC1, nor be pregnant or breastfeeding.

What is being tested?

The trial tests Trappsol Cyclo (hydroxypropyl betacyclodextrin) administered intravenously at a dose of 2000 mg/kg against a placebo in patients with NPC1. It aims to assess safety, tolerability, and effectiveness compared to standard care.

What are the potential side effects?

While specific side effects are not listed here, participants will be monitored for any adverse reactions due to Trappsol Cyclo treatment which could include issues related to infusion such as discomfort or allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My weight is between 4.5 kg and 125 kg.

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I can travel to the trial location when needed.

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I am experiencing at least one symptom related to my nervous system.

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I have been diagnosed with NPC1.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I've had severe, uncontrolled seizures needing medication in the last 2 months.

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My kidney function is reduced, with a filtration rate below 60ml/min.

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My liver disease is not caused by NPC1.

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I haven't taken any experimental drugs or leucine in the last 3 months.

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I had a liver transplant less than a year ago or am planning to have one.

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I have signs of acute liver disease, like jaundice or pain in my upper right abdomen.

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I do not have any symptoms related to my nervous system.

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I have not taken curcumin or fish oil in the last 12 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline in 4-Domain NPC Severity Score (US only)

Change from Baseline in 5-Domain NPC Severity Score (ex-US)

Secondary study objectives

Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale

Change in adaptive behavior as measured by Vineland Adaptive Behavior Scale II

Change in ataxia as measured by Spinocerebellar ataxia functional index

Other study objectives

Caregiver Global Impression of Change at 24 hours post infusion

Change from Baseline in Liver function as measured by liver enzyme assessments

Change from Baseline in Respiratory function measured by Forced Expiratory Volume in 1 second

+5 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Open Label sub-study for Infants up to age 3Experimental Treatment1 Intervention

Up to 12 patients age 0 - 3 yrs in countries following EMA guidance may be enrolled in this open label sub-study. All patients will receive 2000 mg/kg hydroxypropyl betacyclodextrin (Trappsol Cyclo) diluted with 0.5N saline at the clinician's discretion over 6.5 hours every 2 weeks. Outcome measures are safety, clinician and caregiver impressions.

Group II: ExperimentalExperimental Treatment1 Intervention

Intravenous administration of 2000 mg/kg hydroxypropyl betacyclodextrin (Trappsol Cyclo) (based on body weight) diluted with 0.5N saline over at least 6.5 hours every 2 weeks

Group III: Placebo comparatorPlacebo Group1 Intervention

Intravenous administration of 0.5N saline over at least 6.5 hours every 2 weeks

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Hydroxypropyl-beta-cyclodextrin

2017

Completed Phase 2

~30

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Niemann-Pick Disease, particularly type C1, include miglustat and hydroxypropyl betacyclodextrin (such as Trappsol Cyclo). Miglustat works by inhibiting the synthesis of glycosphingolipids, which reduces the accumulation of these lipids in cells. Hydroxypropyl betacyclodextrin solubilizes and mobilizes cholesterol, facilitating its removal from lysosomes where it accumulates due to the defective NPC1 protein. These mechanisms are crucial for Niemann-Pick Disease patients as they directly target the storage of lipids and cholesterol, which is the primary cause of cellular dysfunction and the progressive neurological decline seen in the disease.

Relative acidic compartment volume as a lysosomal storage disorder-associated biomarker.