In most clinical trials, the patient population is randomly split into two blinded groups. One group is given the drug, and the other group given a placebo or "control", to determine if the drug has an effect. This is not ideal for a condition like RCDP where there simply aren't enough patients, and the condition is severe and clinically diverse.
In ultra-rare conditions, performing a placebo trial is often not feasible or ethical, so an acceptable alternative is to create a baseline understanding of the natural history of the disease, and then determine whether treatment results in improvements in any of the historical measurements.
With this approach it is critical to clearly define what RCDP looks like without treatment. As such, without the involvement of patients in the Natural History Study, it will be impossible to assess the clinical effect of PPI-1040. Without solid natural history baseline data, it will be impossible to to obtain an approval for PPI-1040 as a treatment for RCDP, even if it appears to have beneficial effects.
Dr. Michael Bober and his team are currently managing a registry called "The Rhizomelic Chondrodysplasia Punctata Registry at A.I. DuPont Hospital for Children", supported by RhizoKids International. This registry consists of both a retrospective component, which involves the collection and consolidation of medical records, and a prospective survey component where participants are contacted regularly by email to complete surveys designed to assess various components of the disease. Using available medical records can provide information on a disease and how it is commonly treated, but is limited by the fact that the data available is only what is collected during the care of each patient. As such, each patient will have a different set of assessments, performed at different intervals and at different facilities. The registry has already resulted in publications detailing cardiac and spinal complications, as well as RCDP-specific growth curves. This information will be valuable for the clinical trial, but is not sufficient to act as a stand-alone control group. Therefore, a prospective Natural History Study is required.
Natural History Study
The clinical development team at Med-Life Discoveries together with Dr. Bober's team at A.I. duPont Hospital for Children are currently finalizing the design of the Natural History Study. Unlike a registry, a Natural History Study is designed just like a clinical trial, but without the addition of a therapeutic intervention. As such, the Natural History Study will have inclusion and exclusion criteria, a defined list of assessments that will be completed on each patient, and a schedule for repeating these assessments. The assessments used in the study will be standardized, allowing for comparison of the data between patients, as well as within a single patient over time. To generate the data required, the study will enroll patients with RCDP who will then be asked to undergo a variety of clinical assessments, both at the A.I DuPont Hospital for Children as well as in their home. Before initiation of the study, it is important that all measurements to be considered for therapeutic intervention be finalized, because if a function or endpoint is excluded from the Natural History Study, it can’t be later added during the treatment phase. That means that all potential tools need to be evaluated in advance of enrollment of the trial. On occasion, we may ask for volunteers from the RCDP community to provide feedback on the relevance and feasibility of some assessments, as well as to pilot them on individuals with RCDP. These opportunities will be updated regularly on this site. For more information on ongoing activities and how you can get involved, see here.
Quality of Life Questionnaire
As many of the parents know, an RCDP-specific quality of life questionnaire is being designed by Dr. Mousumi Bose. The purpose of the questionnaire is to better understand and define some of the primary issues that RCDP children face on a daily basis in such a way that any improvements during a trial might be captured objectively. Thank-you to those parents who have participated to date. Your input is much appreciated! We will be asking for your continued support and input as we work on finalizing and validating the survey in the coming months.
Currently, assessments that are to be used as part of the official natural history study are being finalized. This includes a few wearable tech devices and a simple finger-prick blood collection test to monitor plasmalogen levels, which is much (much) easier to do than a venous blood draw.
Although there is a lot of work to do, the current goal is to have the protocol finalized before the end of 2018, with the first patient enrolled early in 2019.