blood processing device to treat children with severe sepsis and/or multiorgan failure
Acute kidney injury (AKI) is a serious condition that may lead to severe deterioration in kidney function, oftentimes resulting in multiorgan failure. This condition arises from a variety of medical conditions including sepsis, cardiac surgery, and drug toxicity, Renal replacement therapy (RRT), the process of replacing the normal blood-filtering function of the kidneys, is occasionally successful in treating AKI, but despite this approach, severe AKI with multiorgan failure in pediatric populations continues to have a high mortality rate approaching 50%.
A team, led by University of Michigan’s David Humes, M.D., is developing the Selective Cytopheretic Device (SCD), a biomimetic membrane cell processing device designed specifically for ICU pediatric patients with AKI and multiorgan failure who require RRT.
“When a patient has AKI, especially with severe sepsis, there is a tremendous increase in the activation of circulating white blood cells with the excessive production of cytokines (small proteins that help control the activity of other immune system cells),” explains Humes. “The body is overwhelmed by this excessive amount of cytokines, also known as cytokine storm, and starts to shut down.”
To address the problem, the SCD treats the blood through continuous cell processing of the circulating white blood cells’ inflammatory activity. This leads to a measurable decrease of excessive inflammatory response and normalizes it to an immunomodulatory state. This treatment effect allows the patient to heal damaged organs.
In order to safely use on pediatric patients, a smaller SCD compared to adult devices has been specifically designed for treating small children. This results in a smaller extracorporeal blood volume circuit and a safer treatment profile.
Significant Need
The majority of current and new therapeutic approaches to treat AKI are targeted towards adults. Since these adult systems were not designed to treat small children, pediatric patients are exposed to many risks due to the need for higher blood flow rates and less sensitive volume removal sensors commonly used in adults.
Compelling Science
The SCD utilizes a biomimetic membrane to preferentially and selectively bind the most activated leukocytes, also known as white blood cells, of the blood flowing through the device. When the blood of patients with systemic inflammation due to AKI is processed through the SCD, it effectively reduces the activated leukocytes and the inflammatory mediators that lead to organ failure and death. In addition, the most proinflammatory monocytes, a special white blood cell in the circulation, are also bound, resulting in a shift from a general inflammatory/septic state, to a more quiescent, reparative state. This continuous cell processing of the SCD results in a reduced inflammatory response in a variety of preclinical and clinical disorders and improves clinical outcomes.
Competitive Advantage
RRT has had little advancement over the last two decades, and the majority of new therapeutic approaches in development are targeted to treat adults. The work funded by the Frankel Innovation Initiative will support a prospective, single-arm, multicenter U.S. clinical trial designed to evaluate the safety and efficacy of the SCD treatment on AKI requiring CRRT in pediatric patients.
Overall Commercialization
- Intellectual Property: Multiple patents covering the SCD technology; additional patents may be obtained as clinical trials continue
- Commercialization Strategy: Currently licensed to a medical device company to commercialize this technology
- Regulatory Pathway: Approval utilizing FDA Humanitarian Device Exemption (HDE) for marketing and sales to pediatric hospitals
- Product Launch Strategy: First clinical trial completed; second clinical trial is in progress. This clinical data will support submission of an HDE to the FDA for review and approval.
Milestones
- Submission and FDA approval of IDE for a potential of a third clinical trial, PED-SCD-03, using a smaller SCD for infants, after preclinical large animal testing.
- IRB submission and approval at all clinical sites; clinical trial agreements executed at all clinical sites for current clinical trial, PED-SCD-02, to treat children weighing 10-20 kg.. Clinical trial initiated at Cincinnati Children’s and other sites.
- Continuation of enrollment with anticipated enrollment of 1 patient per month from all sites. Preparation of IDE supplement to include patients weighing 5 to 10 kg body weight.
- Completion of study enrollment and closing the clinical data and compiling the safety and efficacy reporting to the FDA. A third year of FFMI funding will be considered if the smaller SCD demonstrates safety and efficacy in the preclinical experiments for a clinical trial in infants.
