Trappsol® CycloTM Clinical Studies

Frequently Asked Questions

(Updated June 20, 2017)

A. Clinical Trials and Patient Participation

1. What is a clinical trial?

Clinical trials are conducted to determine whether investigational drugs are safe and effective. Carefully conducted clinical trials are the fastest and safest way to find potential future treatments that work in people. Investigational drugs go through several phases of clinical trials. The typical Phases that clinical trials go through are Phase I, Phase II and Phase III and the information from these Phases is then used to support a new treatment obtaining regulatory approval to be prescribed as a medicinal product.

2. What do the three Phases focus on and what information is obtained from them?

Phase I trials focus on determining safety of the investigational study drug by identifying possible unwanted side effects of the treatment. During Phase 1 trials the safety across a range of doses of the treatment is also investigated. When Phase I trials are completed information on the initial safety of the treatment across a range of doses is available.

Phase II trials focus on determining the effectiveness of the investigational study drug. Phase II trials gather preliminary information on whether (or not) an investigational drug works in a group of people who have a particular disease or condition.

Phase III trials are designed to assess the effectiveness of the new intervention and, thereby, its value in clinical practice. Phase III studies are randomized controlled multicenter trials on larger patient numbers than have been treated in the Phase I and II trials. They are aimed at being the definitive assessment of how effective and safe the drug is prior to regulatory approval.

Clinical trials of drugs may not fit into a single phase as described above. For example, some may blend Phase I to Phase II together to form a Phase I/II trial and this may happen when the treatment under development is intended to be used in a rare or orphan disease.

3. What is a randomized clinical trial?

A randomized clinical trial is one in which the participants are assigned by chance (i.e., randomly) to separate groups that compare different study interventions. Neither the researchers nor the participants can choose which group. Randomization gives each participant an equal chance of being assigned to any of the groups. Using chance to assign people to groups allows researchers to better understand the effects of the intervention in the study participants.

4. What is a placebo? Do the studies being conducted with Trappsol® Cyclo™ have a placebo group?

Placebos are inactive pills, liquids, or powders that have no therapeutic value. In clinical trials, placebos are often given to one group while the experimental treatment is given to another group to assess the experimental drug's effectiveness. The Trappsol® Cyclo™ studies will not use placebos and all groups in the studies will receive the investigational treatment.

5. What does double-blinded mean?

A clinical trial that is double-blinded is one in which neither the trial participants nor the study staff knows which participants are receiving which intervention. Imposing a "double-blind" is one way trials are designed to produce objective results, since the expectations of the doctor and the participant about the experimental drug do not affect the outcome.

6. Why should I participate in a clinical trial?

Clinical trials answer questions we have about potential new treatments-whether and how well the experimental treatment works, and whether it is better than currently existing medications. The only way that doctors and researchers can get answers to these questions is for people with the disease to help by taking part in a study. At the same time that you are helping the science move forward, you have the opportunity to receive excellent care and be among the first to receive a new drug that might in the future offer improvement in the treatment of your disease. If you decide to participate in a clinical trial, all the potential risks will be explained to you so you are fully informed before you make your final choice to participate.

B. What is Trappsol® Cyclo™ and what Clinical Trials are Planned to Investigate the Use of this Treatment?

1. What is Trappsol® Cyclo™

Trappsol® Cyclo™ is a cyclodextrin-based experimental treatment being studied to treat Niemann-Pick Type C (NPC1). Cyclodextrins are rings of sugar molecules that form a donut-like structure and that have the capacity to release cholesterol from NPC cells. The way in which this experimental treatment works is not fully understood but laboratory experiments have shown that it can potentially remove the harmful cholesterol build up from the cells caused by a defect in a protein in people with NPC1. If left untreated, cholesterol builds up in the cells ultimately leading to organ damage.

2. What clinical trials are taking place with Trappsol® Cyclo™

There are two clinical studies currently taking place simultaneously. The first study is a Phase I study which is designed to investigate the pharmacokinetic properties of Trappsol® Cyclo™ and its effects on potential biomarkers of NPC1. This study is taking place in the USA (see ClinicalTrials.gov Identifier: NCT02939547).

The second trial is a combined Phase I/II trial which is designed to investigate the pharmacokinetic properties and the preliminary efficacy of Trappsol® Cyclo™ in patients with NPC1. The study is taking place in the UK and Sweden, and expected in Italy (see ClinicalTrials.gov Identifier: NCT02912793).

3. What is the design of the Trappsol® Cyclo™ Phase I clinical trial that is taking place in the USA?

This study is being conducted to find out whether Trappsol® Cyclo™ is safe at 2 different dose levels of the product and to determine what effects it has on people who have NPC1. Approximately 12 participants will be asked to join in this research study for up to 20 weeks (w) in total (including screening, treatment and follow-up). Recruitment is expected to take 6- 9 months.Participants will receive treatment by an intravenous infusion every two weeks. The study will look at what the body does to the drug as well as what the drug does to the body by taking and examining blood and urine samples. Samples of cerebrospinal fluid (CSF) will be taken by lumbar puncture during and following the first and subsequent treatment doses. Liver and skin biopsy specimens will also be taken. Cholesterol metabolism will be investigated in liver samples and splenic size and hepatic size and elasticity will be assessed by ultrasound. Patients will also have their hearing tested, and be asked questions by their doctor as well as completing questionnaires to help assess any changes in their condition during treatment.

4. What is the Trappsol® CycloTM Phase I/II clinical trial that is taking place in Europe?

This Trappsol® Cyclo™ clinical trial is a Phase I/II clinical trial will evaluate the safety and preliminary efficacy of this experimental treatment at three different dose levels. The Phase I part of the study will assess the safety of the drug and the Phase II part will focus on the longer-term efficacy and safety of the drug. The treatment will last 48 weeks with intervention given every two weeks. The study is expected to take 56 weeks in total including screening and follow up. Approximately 12 participants will be asked to take part in this research study. Participants will be placed into one of the three dose groups based on chance (called randomization, which is explained above). This means there will be four participants in each dose level group. Three doses will be tested in this study so that physicians and scientists can try to understand how the experimental treatment impacts cells in the body. All participants will receive the experimental intervention. The study will be double-blinded, meaning neither the patient, the caregiver, the investigator or the outcomes assessor will know which patient is receiving which dose level during the trial.

5. If I participate in one of the studies can I leave the study before it completes?

Yes, you have the right to leave the study at any time and for any reason.

6. Will I be compensated for travel expenses?

Yes, CTD Holdings, the sponsor of the study will cover travel expenses to the study site for the study participant and one caregiver, along with a daily stipend to support meals and hotel during the stay. Since this trial will involve treatments every two weeks and an overnight stay following the first treatment, plus assessments, participants may elect to travel back and forth from home to the study site or stay near the study site for the period of the trial. The sponsor is willing to support either scenario provided that eligible patients can commit to participation in the full study.

7. Do I have to pay to participate or for any for the treatment costs?

The medical care, exams, and laboratory tests that are part of the study will be provided at no charge. You are not required to pay to participate in the study.

8. May I continue to see my own doctor if I enroll in one of these trials?

Yes, you should continue to see your regular doctor(s), but a study physician will oversee your study treatment and participation in the study.

9. What is the difference between these trials and other trials that are available for NPC using cyclodextrins?

These trials offer the investigational drug through a different method of delivery via an injection into your vein (intravenous) rather than through an injection into the fluid space around your spinal cord (intrathecal). It is important to test and understand how patients may be helped based on different ways the drug is delivered to your body.

10. What side effects might I experience if I participate in one of these studies?

CTD Holdings has more than 7 years' experience with usingits cyclodextrins intravenously in NPC patients through regulator-approved compassionate use programs globally. Based on this experience,
we expect only minor side effects, such as rashes, nausea, vomiting, and fever to occur. These side effects have been managed with standard treatments in patients in the compassionate use program. CTD's cyclodextrin, however, is an investigational drug and its safety thus has not been established.

11. Who is sponsoring these studies?

These studies are being conducted by CTD Holdings, Inc., a public, clinical-stage biotechnology company that develops cyclodextrin-based products for the treatment of disease.

12. Where can I get more information about the studies?

To learn more about the studies, visit ClinicalTrials.gov, the US government's repository for information on clinical trials being conducted in the US and abroad. Details on CTD's Trappsol® Cyclo™ trials can be found under:

Phase I: https://clinicaltrials.gov/ct2/show/NCT02939547

Phase I/II: https://clinicaltrials.gov/ct2/show/NCT02912793

You can also visit CTD's website to learn more about the company, the research and the science, and the people supporting this trial: http://www.ctd-holdings.com/

13. What resources are available to me to make a decision about participation?

You should speak to your doctor to decide whether participating in a clinical study is right for you. There are a number of NPC patient advocacy groups ready to help with information on clinical trials. You should look to those that provide objective views on multiple trials so that you can make the most informed decision on what is right for you and your family.

Other helpful terms to know:

  • Adverse effect: An unwanted side effect of treatment
  • Dose:The amount of medicine taken at one time
  • Side effect:Any undesired actions or effects of a drug or treatment. These may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental drugs must be evaluated for both immediate and long-term side effects.
  • Sponsor:An individual, company, institution, or organization that begins a clinical trial and takes responsibility for the initiation, management, and/or financing of that trial, but who does not actually conduct the clinical trial