Cheryl Demos Fludas, Former Head of Clinical Operations at Myrtelle:

Q: Choosing to decide to enroll oneself or a loved one (especially a child) in an experimental clinical trial can be overwhelming.  Can you provide a brief overview of that process and what happens once a patient is identified, screened and enrolled?

A: The process begins with determining if the trial is right for your child and whether your child qualifies for the trial. The criteria for eligibility are established in advance and documented in a clinical protocol. The trial physician (also called study doctor) is responsible for explaining the purpose of the trial, who qualifies for the trial, the number of visits and medical tests, the risks of the investigational treatment and the possible benefits – this process is called Informed Consent. 

 Physicians who conduct clinical trials are called investigators, because a clinical trial is an investigation to assess safety and efficacy of a novel therapy. These investigators are independent researchers and are not affiliated with the company sponsoring the trial. Investigators agree that they will adhere to the clinical trial rules and procedures, or protocol. The protocol is reviewed by and agreed with FDA and approved by an institutional review board or ethics committee to ensure the protection of the rights and welfare of the patients. The trial must have scientific merit and steps for managing potential side effects of the treatment to reduce risk to the patient.

Investigators determine whether a patient is eligible for the trial using criteria set forth in the protocol. Most study protocols include a set of inclusion as well as exclusion criteria that limits various medical complications or illnesses and medications that the patient may be taking that would interfere with the effect of the gene therapy on the disease.  The child must meet all inclusion criteria and none of the exclusion criteria.

Participation in a gene therapy trial is a huge commitment of time that impacts the whole family: parents, caregivers, and even siblings. Families must take time away from home, work, and/or school and sometimes travel great distances to medical centers (also called clinical sites) to receive the experimental treatment and to complete all the required study procedures and testing. These evaluations are necessary to assess whether the treatment is safe and effective.

Another important factor to determine eligibility is the willingness and ability of the family to return to the clinical site for follow-up visits as well as adhere to all the trial’s requirements, such as completing necessary examinations and following the investigator’s instructions. Typically, gene therapies involve just a single dose, but the child must be followed for 5 years or possibly more for evaluation of long-term efficacy and safety. The first year after gene therapy for Canavan Disease requires many evaluations, including blood draws, imaging of the child’s brain, and a number of visits to the physical therapist in order to assess safety and efficacy of the gene therapy.

If clinical trial patients do not return for follow-up visits, valuable data will be lost. An accurate assessment of safety and efficacy of the gene therapy requires that patient measurements be collected over time so that any changes, such as improvements in the patient’s disease, can be documented. Loss of these data is very detrimental to the clinical program and can jeopardize the further development of the therapy as -well as the safety of the patient.  Myrtelle’s goal is to learn from the trial and to improve the lives of the patients with Canavan disease — not just the patients in the given trial, but the future patients as well.

Robert Lober, MD, PhD, FAANS, Co-Principal Investigator and Associate Professor of Pediatrics at Wright University Boonshoft School of Medicine and Attending Neurosurgeon at Dayton Children’s Hospital Dayton, OH:

Q: How is it explained to a patient/family what will be expected of them during their treatment?  How are expectations of the trial managed?

A: We allocate as much time as necessary for families to understand their own critical roles as partners in the clinical trial.  Safe administration of gene therapy and post-treatment care is an intricately planned, highly orchestrated process.  It requires expert healthcare providers in addition to dedicated family members willing to undergo the inconveniences of travel, hospitalization, medical visits, and sometimes, uncomfortable diagnostic tests.  

It is vitally important for trial participants to understand the relevance and necessity of these measures to ensure the safety and efficacy of gene therapy.  Despite absolute dedication of our families to the program, it may still be difficult to comply with all aspects of the protocol for medical and social reasons.  Study subjects come from all over the world, and travel may be particularly difficult with children who have special needs, such as those with Canavan disease.  Therefore, we engage in regular discussions about family needs in relationship to the study schedule and work tirelessly with families to alleviate obstacles in their path.

Armen Asatryan, MD, MPH, Chief Medical Officer:

In the rare disease space, most patients enroll in a clinical trial because treatment options are limited or there simply are none.  Some have described it as receiving the “golden ticket” when chosen to enroll, but can you explain clinical trial attrition and the ripple effect?

A: Indeed, access to clinical trials in a rare disease setting can be limited due to scarcity of drug development programs for these diseases. As an example, a more mainstream disease may have several dozens of active clinical trials, but for any given rare disease there may be only one or two clinical trials. Further, a patient must meet the trial’s eligibility criteria in order to enroll in the trial and receive the study drug (e.g., the gene therapy). 

Once enrolled in the trial, there is a substantial time and effort commitment needed from the patients and their families/caregivers in order to participate in all the trial activities. These activities can range from tasks as simple as measuring pulse and blood pressure to getting blood draws and doing imaging, such as CT or MRI scans. Completion of all these procedures can take up to several days and thus can be taxing on patients and families/caregivers. However, the clinical data generated in these visits are of crucial importance to the drug development – specifically, these data determine whether the drug would be advanced into the next phase(s) of development and ultimately brought to the patients around the world. If these data are lacking or incomplete due to missed trial visits, then the companies working on developing these therapies will not be able to obtain adequate amount of information about the drugs, and this can delay approval of these drugs, which means that patients would not be able to get these therapies. This also means that all the efforts and investment of time and resources spent up to that point could be in vain if further drug development is terminated. Hence, it is extremely important for the patients and families/caregivers to understand all the relevant specifics about the clinical trial, including various procedures done during the trial, length of the trial, any travel needed, and other important details. The study doctor (also called principal investigator) should describe all these details to the prospective trial participants (and/or to families/caregivers) and also provide an opportunity to ask questions. 

Jordana Holovach, Vice President, Head of Communications & Community:

Q: Having gone through 2 gene therapy trials with your own son, can you share some of your insight that might be helpful families following the clinical trial path?

A: Deciding to enroll your child in an experimental trial elicits hope as well as trepidation.  Educate yourself, seek the help of others in making your final decision including experts in the field and never feel apprehensive about asking questions (especially during the informed consent process).  Being well-informed on what will be expected and the sacrifices that might have to be made as a family are critical because your decision to enroll your child comes with the responsibility of following protocol and is critical to other families seeking treatment for their children as well.  The viability of the trial you’re participating in and of future trials, and ultimately drug registration and commercialization depend on each family’s commitment to attend follow-up appointments in which important data are obtained from the clinical study’s examinations and testing.  These exams are equally important for monitoring safety and keeping the principal investigators and clinic team abreast of your child’s progress and care which is of paramount concern.

For most families, travel is a part of clinical trial enrollment, including frequent air travel.  In preparation for this, I would suggest not flying with your child’s primary wheelchair.  The risk of damage or losing pieces of the chair that might be removed by airline personnel for storage under the plane is too high and unfortunately these types of issues commonly arise.  If possible, take an alternative piece of equipment or modified stroller that folds and is less likely to incur damage during the flight.  If travel is too far, inconvenient, or presents legitimate concerns, I would highly suggest considering a longer stay near the site for follow-up appointments and care.  Of course, feasibility of this is highly dependent for each family.  

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