About the TransportNPC Clinical Trial

Transport NPC is a phase 3 clinical trial to evaluate the safety and efficacy of the investigational therapy Trappsol® Cyclo™ (hydroxypropyl beta cyclodextrin) for the potential treatment of Niemann-Pick disease type C1 (NPC1). It is currently the largest and most advanced clinical research program underway to identify a treatment for NPC. Trial sites are now enrolling patients in the TransportNPC trial. To find the trial site nearest you, click here.

Since Cyclo Therapeutics began work to develop a treatment for NPC in 2015, we have heard from many members of the NPC community about the importance of having an approved therapy available. There has also been a great deal of interest in what patients can expect by participating in the TransportNPC clinical trial:

  • The trial will enroll 93 patients aged three years or older and will last 96 weeks. However, the first review of the results of the trial will be completed after all subjects have been treated for 48 weeks. If the results indicate that treatment is providing benefit to patients, Cyclo will decide whether to file for market authorization for Trappsol® Cyclo™ based upon the 48 week data.
  • During the trial, some patients will be treated with Trappsol® Cyclo™, which is a formulation of a drug called hydroxypropyl beta cyclodextrin, and some will be treated with placebo. It is important to note that patients who show a substantial decline in their health after 48 weeks may be switched to an "open label" arm of the trial where all patients are treated with Trappsol® Cyclo™.
  • In the trial, Trappsol® Cyclo™ will be administered intravenously. In previous clinical trials, intravenous administration has been associated with a favorable safety profile and the ability of the active ingredient to cross over into the brain, which is an important goal in treatment for NPC.
  • Cyclo is also conducting a small sub-study of pediatric patients up to age three years. This study will seek to enroll up to 12 pediatric patients with NPC1 outside the U.S. All patients in the sub-study will receive Trappsol® Cyclo™. The goal of the sub-study is to evaluate safety and better understand clinical and caregiver impressions of efficacy.

If you have any questions about the Transport NPC trial, please email them to Lori Gorski at lori.gorski@cyclodex.com.

Key points about the TransportNPC trial

  • The TransportNPC study will enroll NPC1 patients older than age three and including adults. Cyclo Therapeutics will post information about new sites on clinicaltrials.gov as they become available. You may also ask your treating physician for information about locations that are near you.
  • Eligible patients will be randomized 2:1 to receive investigational drug or placebo.
  • The study will last 96 weeks and include an interim analysis at 48 weeks. We understand that 96 weeks can feel like a long time. If the trial shows positive results at the 48-week mark, Cyclo may be able to accelerate the time to completion of the trial.
  • We have designed the TransportNPC trial to provide the essential levels of information to regulators about safety and efficacy that can allow us to obtain marketing approval for Trappsol® Cyclo™ for the treatment of NPC1.

Questions about the TransportNPC trial and Trappsol® Cyclo™

What is hydroxypropyl beta cyclodextrin / Trappsol® Cyclo™?

Trappsol® Cyclo™ is an investigational drug containing a proprietary formulation of cyclodextrins. Cyclodextrins are rings of sugar molecules that bind to cholesterol. As a result, they have the potential to help move cholesterol that collects in cells in NPC1 patients to areas where it can be metabolized and removed.

What are the details of the Phase 3 study?

The study will enroll 93 participants with NPC1 who are at least three years of age and have a moderate rate of decline based on factors including the age of the patient and severity of disease. Participants will be randomly assigned to receive Trappsol® Cyclo™ or placebo intravenously every two weeks for two years. The intravenous infusions last 6-7 hours each, and participants, physicians, and company representatives will not know who is receiving Trappsol® Cyclo™ or placebo. Participants will receive infusions at the clinical sites and complete periodic safety and efficacy assessments.

For US-based participants, the primary efficacy measure of the study is the change between groups in speech, swallowing, and motor skills including hand function and walking at both the 48-week and 96-week marks. For participants outside of the US, the primary efficacy measure is the change between groups in speech, swallowing, motor skills including hand function, walking and cognition at both the 48-week and 96-week marks. After 48 weeks, a group of independent medical experts will review the results. If the results indicate that treatment is providing benefit to patients, it could be possible for Cyclo to file for market authorization for Trappsol® Cyclo™ based on the 48 week data. If more definitive data are needed, the experts may recommend having the trial continue for another year. After the study is completed, participants will be eligible to receive Trappsol® Cyclo™ for two years in a long-term extension study.

What types of patients are you enrolling in this study?

Information about how to qualify for the study can be found at clinicaltrials.gov. In general, we are enrolling pediatric and adult patients with a confirmed diagnosis of NPC1. Patients who have previously been treated with hydroxypropyl beta cyclodextrin in clinical trials or in expanded access programs are not eligible to participate in this study.

What are the goals of the study?

This study is designed to evaluate whether treatment with Trappsol® Cyclo™ plus normal standard of care slows disease progression or leads to improvement in certain features of disease compared to a placebo plus standard of care.

What is the primary outcome measure of the study?

As a primary outcome measure, this study will assess changes in several features of the disease, including the ability to speak and swallow as well as changes in motor skills. There are some differences in outcome measures in clinical trials in the US and EU.

The study mentions 48 weeks and it mentions 96 weeks. Can you explain?

Once all 93 patients have been treated for 48 weeks, a group of independent medical experts will review the results. If the results indicate that treatment is providing benefit to patients, it could be possible for Cyclo to file for market authorization for Trappsol®Cyclo™ based on the 48 week data. If more definitive data are needed, the experts may recommend having the trial continue for another year. After the study is completed, participants will be eligible to receive Trappsol® Cyclo™ for two years in a long-term extension study.

Why do you need a placebo arm in such a long study and in such a serious disease?

The design of this study was created with guidance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based upon previous experiences with Niemann-Pick and other rare diseases. It is designed to deliver the level of data necessary to rigorously assess the efficacy and safety of Trappsol® Cyclo™ to support regulatory approval.

The use of a placebo arm can help show whether there are clear and meaningful benefits associated with treatment with an investigational drug. It is often the fastest way to assess clinical benefit and can therefore help to speed up the path to approval for a new drug.

During the time that patients participate in this study, their health will be monitored closely. Any patients who experience a substantial decline by the end of the first year will have the option to switch immediately into the open label portion of the study where they will have access to treatment with the investigational drug.

Why is the route of administration intravenous?

Cyclo Therapeutics chose the IV route of administration for this study based on data showing a positive effect on survival and symptomology in a mouse model of NPC, coupled with the company's extensive experience with IV use of the drug in compassionate programs, and the company's early clinical trial data. Results using IV administration show a favorable safety profile, biochemical effects on cholesterol processing, and biomarker data demonstrating effects on cholesterol and lipid clearance and on potential neuroprotection. Clinical studies and compassionate use programs have suggested improvements in the ability to walk, speak and swallow, fine motor skills, and cognition, along with reductions in liver and spleen size and reduction in interstitial lung disease. These results indicate that IV administration of Trappsol® Cyclo™ has the potential to treat both the neurologic and systemic manifestations of NPC.

IV administration is routinely performed and a low-risk procedure in many treatment contexts. An ongoing extension study has shown that the drug may be administered safely in the home setting.

What is the safety profile for Trappsol® Cyclo™?

In clinical trials and individual expanded access programs, Trappsol Cyclo generally has exhibited a favorable safety profile, which has allowed Cyclo Therapeutics to proceed with its Phase III TransportNPC trial. One adverse event that has been observed in formal trials and in compassionate use programs was localized infusion reactions, not uncommon for IV drug administrations and which subsided in all cases, and in one case a severe hypersensitive reaction which may have been related to underlying conditions and which resolved in a fperiod of days. Other adverse events were transient hearing losses, which were not perceived by patients or their families, and which were detected by routine monitoring. The TransportNPC trial will monitor hearing closely along with infusion reactions out of an abundance of caution for patient safety. If you are interested in participating in the TransportNPC trial, the Informed Consent Form contains a detailed description of the drug's safety profile and information on adverse events observed to date.

Can patients who were previously treated with hydroxypropyl join the study?

Previous research has shown that any prior treatment with hydroxypropyl beta cyclodextrin can have a lasting effect on patients. As a result, we are unable to enroll any patients who have previously received any form of hydroxypropyl beta cyclodextrin by any route of administration. This is necessary to ensure that the results of the trial are based exclusively on the impact of treatment with Trappsol® Cyclo™.

Are there any options available through Cyclo Therapeutics to receive Trappsol® Cyclo™ apart from the Phase 3 trial?

The FDA recently authorized physicians to substitute other formulations of hydroxypropyl beta cyclodextrin (VTS-270, also known as adrabetadex, and Kleptose) for Trappsol® Cyclo™ for intravenous administration. Patients who have been treated with other formulations of hydroxypropyl beta cyclodextrin via intrathecal or intravenous administration are eligible to switch to intravenous Trappsol® Cyclo™ with support from their physicians. Cyclo Therapeutics has committed to providing Trappsol® Cyclo™ at no cost in such situations.

For more information on how to receive Trappsol® Cyclo™ apart from the Phase 3 trial, contact Cyclo Therapeutics via lori.gorski@cyclodex.com..

Are travel costs covered for participants in the trial?

Cyclo Therapeutics will provide financial support for necessary travel for patients to study sites.

Where can I get additional information?

Updated information about the TransportNPC trial is available at clinicaltrials.gov. You can also email any questions to Lori Gorski, Global Head of Patient Advocacy at Cyclo, at lori.gorski@cyclodex.com.