Heroes still exist in the world, and this time one took the form of a 35-year old neurologist and principal investigator named Dr. Thomas Pitts. TrialSite News recently highlighted how this physician saved the life of Amy De Vos, a 45-year old who fought for her life battling a deadly case of SARS-CoV-2. Her physician at Upper Valley Medical Center heard of a small study Pitts was conducting with New York State’s Hudson Medical. Dr. Pitts had studied other coronaviruses and uncovered something known as a “complement” was attacking patients’ lungs. The young principal Investigator’s hypothesis: that a complement inhibitor known as Eculizumab (Soliris) may help stop advancing respiratory illness associated with COVID-19. TrialSite News had the honor of a brief interview.
Dr. Pitts hypothesized that while COVID-19 is a provocateur, it is often the patient’s own disproportionate immune response that deals the most devastating, and often fatal, blow. A specific part of the immune system, known as the complement, has been shown to cause such damage in other types of coronaviruses. In the SOLID-C19 study, Eculizumab was used to modulate the activity of the distal complement, preventing the formation of the membrane attack complex.
Dr. Pitts told us that by modulating this portion of the immune response, mortality could potentially be avoided and the patient given more time to recover from SARS-CoV with ongoing care. He informed us that the development of an antiviral therapy and vaccine is of vital importance; also important are methods (such as Soliris) to deal with critical COVID-19 cases involving ARDS, where the body’s own self-destructive response to the attacking pathogen would not only complement other approaches but also reduce the chance of death. This is a fundamental goal that the recent Remdesivir study couldn’t achieve, for example.
Working with Regulators
Dr. Pitts reported to TrialSite News that he had to navigate administrative and regulatory pathways to ensure that the U.S. Food and Drug Administration (FDA) would approve the emergency-access study. The doctor hinted that it was a bit of a humbling experience as one lone physician navigating a whole regulatory authority. After a number of interactions—with a few uncomfortable twists and turns—he was finally invited to conduct the study on a case-by-case basis. He was required to secure the approval of the Emergency IND for each patient, which he accomplished. Dr. Pitts also successfully ensured buy-in from Alexion Pharmaceuticals, the makers of Soliris.
Titled “Soliris to Stop Immune Mediated Death in COVID-19 Infected Patients: A Trial of Distal Complement Inhibition,” Dr. Pitts commenced the emergency access-study involving up to five critically ill COVID-19 patients. Dr. Pitts, who is affiliated with Hudson Medical, established the following Endpoints:
- Time in the ICU
- Time on the Ventilator
To participate in this study, a patient had to be 18 or over, have a confirmed COVID-19 infection, acute respiratory distress syndrome, and be in the ICU in the hospital.
Patients Close to Death
It is important to note that the patients in this study were in critical condition—that is, according to Dr. Pitts, “end state intubated full on ARDS (acute respiratory distress syndrome).” He noted that the same critically ill patients in the general population at this stage had an 86-97% mortality rate. Limitations were a challenge—for example, an average two-day lag time from patient identification, to FDA approval, to drug shipment, and to administration.
As reported in ClinicalTrials.gov, Dr. Pitts noted in the protocol that before administering the treatment, the patient had to receive ceftriaxone IV and that this would continue during the entire therapy. If there was a clinical reason to preclude Ceftriaxone (allergy, etc.) then an alternative prophylactic antibiotic covering Neisseria meningitis would be administered during the therapy. As reported in the Clinicaltrials.gov protocol, the SeroB and Quadrivalent meningococcal vaccines can be given if the duration of the antibiotic therapy becomes unsafe or not feasible. The protocol also noted it is preferred that vaccination is avoided while the patient is acutely ill and that prophylactic antibiotics are used as meningococcal vaccination can upregulate the immune system, possibly worsening the patient’s condition.
Dosing & Care
The standard dosing protocol included Eculizumab 900mg IV every 7 days. Note that Eculizumab is given IV over 30 minutes normally without the need of a pump, but a pump can be used if available. Supplemental doses of eculizumab could be administered if clinically warranted at the discretion of the investigator and clinical team. The team performed Murray scores daily for the first 72 hours and thereafter every other day unless there was a change identified as required by the attending physician. Additionally, the team made complement blood levels every 72 hours. This could be done sooner if there was a clinical inquiry, which would affect clinical decision making and/or after a dose of Eculizumab was given. The duration of this therapy was discretionary based on the clinical team and Dr. Pitts. Dr. Pitts and team did follow-ups at days 7, 14, and 28 after discharge.
As mentioned earlier, these patients were in such critical condition that the probability of mortality was extremely high. This emergency-access study took in patients that were close to death. Of the five patients, one was excluded because his endotracheal tube dislodged. Hence, the emergency-access study (also known as a pilot) could take in four patients. Again, this is in a context of a general population baseline with an 86-97% mortality. Of the four remaining patients, two died and two lived—the latter including Amy De Vos. So the result was a 50% mortality rate.
This pilot, emergency-access study showed that Dr. Pitts’ approach can work. Importantly, the two surviving patients rapidly improved despite having been on ventilators for days with end-stage lung injury. One of the patients also faced a renal injury.
As was reported in multiple publications, including in TrialSite News, Amy De Vos was certain she would pass on—her husband and three children even said goodbye. But with her entry into the emergency-access study, she’s convinced it saved her life.
Finally, Dr. Pitts opened the door for another, larger expanded-access study that will allow the study team to deliver the drug much sooner—for example, the facilities would have the drug on site rather than having to have it shipped for each patient as was the case for the pilot. Moreover, the patients would access the study drug faster. In a bigger, expanded trial, Dr. Pitts expects an even lower mortality rate.
Dr Pitts on Some Takeaways from this Experience
Dr. Pitts—committed, passionate and driven to help patients—is unbelievably humble and introspective as well, a truly honorable man. Originally from Florida, he entered medicine to help others and save lives. He reported that he encountered more bureaucracy than he would have initially expected, given the severity of the situation. But thankfully, the FDA came through to support the study as did Alexion Pharmaceuticals.
First and foremost, Dr. Pitts expresses that sometimes when you know something is the right thing to do, you simply do it. Even if you are all alone—and you must depend on yourself and no one else to navigate medical, scientific and administrative spheres of life to achieve the mission driving you forward.
But he emphasized that you must understand what a clinical study entails and that this involves not just the science and medicine but also the compliance and the administrative elements of the study.
Moreover, he emphasized that immunology is a key topic when it comes to COVID-19. Much of the popular media has focused on anti-viral drugs such as Remdesivir or hydroxychloroquine, but that for those COVID-19 patients in end-stage, intubated full-on ARDS, this represents a different medical problem and hence necessitates different medications. In this case, he utilized the specialized kind of drug called Eculizumab, a human monoclonal antibody directed against terminal complement protein C5. The drug binds to terminal complement protein C5, thereby blocking the complement-mediated destruction of paroxysmal nocutral hemoglobinuria (PNH) red blood cells. Finally, he pointed out that building and nurturing a network is absolutely key to getting an emergency study such as this one done. For example, thankfully he was able to successfully collaborate with the FDA as well as Alexion Pharmaceuticals.
Dr. Thomas Pitts continues his quest to save those COVID-19 patients in severe to critically-ill condition. He was able to overcome a number of obstacles just to get to the opportunity to save two patient lives. He wants to save more lives next time.
Dr. Thomas Pitts, neurologist, is a board-certified Neurology & Clinical Neurophysiologist who received fellowship training at Columbia University Medical Center. He also served as Chief Neurology Resident at Wright State University in Dayton, Ohio. He is a Gold Humanism Honor Society Inductee and currently works as the director of Neurology at Hudson Medical & Wellness in Manhattan, New York.
Call to Action: Dr. Pitts is working on expanding this emergency-access study. If you would like to partner with him, he can be reached here.