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 spent over a year finalizing the design of the Natural History Study. Unlike a registry, a Natural History Study is designed just like a clinical trial, just without the inclusion of a therapeutic intervention. As such, the Natural History Study has inclusion and exclusion criteria, a defined list of assessments that is completed on each patient, and a schedule for repeating these assessments (every 6 months). All study assessments are standardized, allowing for comparison of the data between patients, as well as within a single patient over time. Participants in the Natural History Study will to undergo a variety of clinical assessments, both at the Alfred I. DuPont Hospital for Children as well as in their home. To aid in the organization of travel logistics and facilitate reimbursement of expenses a travel agency which specializes in clinical trial travel has been contracted. If you are interested in participating in the study more information on the criteria, assessments and clinical contacts is available 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 are in the process of testing an initial version of the survey and hope to have a finalized survey included in the Natural History Study in the near future.