Running a COVID Vaccine Trial

There are similarities and differences in running a COVID-19 vaccine trial versus other vaccine trials. Specifically, the pandemic has offered opportunities to conduct trials in a new way, and the availability of patients is making recruitment very easy. However, the emergence of novel COVID variants may impact trial results for sponsors currently running COVID-19 studies. In this interview, Jessica Lee, SVP Clinical Operations and Global Integration at Inovio Pharmaceuticals will discuss her perspectives.

Moe Alsumidaie: What are the challenges of running a COVID trial?

Jessica Lee: One of the common challenges in clinical trials—which became more

pronounced at the onset of the global COVID-19 pandemic—is the need to safely and efficiently plan, design, recruit and ultimately run a clinical trial. However, INOVIO has been uniquely situated to support the fight against COVID-19 in large part due to the flexibility and scalability inherent in the development process for INOVIO’s DNA vaccines.

DNA vaccines are composed of highly characterizable plasmid DNA—small circular pieces of DNA engineered to produce antigens from target pathogens (e.g., viruses, bacteria, and cancer cells)—allowing for rapid, cost-effective scaling and manufacturing. As a result, at the beginning of the pandemic, our DNA vaccine candidate for COVID-19, INO-4800, went from design to human dosing in 83 days. We’ve also seen similar benefits across our 15 programs in development. For example, our DNA vaccine candidate for MERS, INO-4700, took 6.5 months to clinic and had a 95% response rate post-dose 2, as well as a 98% overall response rate.

MA: How could the introduction of new COVID variants impact trial results?

JL: The introduction of new COVID-19 variants is a challenge vaccine developers are currently facing. However, one of the hallmarks of DNA vaccines is the ability to rapidly respond to emerging infectious diseases. In fact, DNA vaccines have the ability to deliver cross-strain protection, covering more than one antibody and protecting against new disease mutations

INOVIO has been closely monitoring the evolution of COVID-19 variants, with a particular focus on the U.K., South African and Brazilian variants. With instances of these variants on the rise and the South African variant expected to be the dominant strain in the United States by March, this is an area of priority focus. INOVIO is currently evaluating the new variant impact on INO-4800, as well as working on a targeted vaccine response through the development of a new variant-match construct.

MA: What plans have you put in place to mitigate operational risks in your COVID trial?

JL: In order to prioritize the safety of our trial participants and staff alike, we have incorporated alternative means of data collection into the protocol that helps preserve study integrity, including telemedicine visits and home collection kits where trial participants can directly ship samples to the testing facility. INOVIO is also leveraging remote monitoring as standard practice and have embraced additional e-solutions, including e-consents and direct data capture to reduce transcription.

MA: How are you getting sites to prioritize your COVID trial?

JL: Multiple factors have contributed to interest in our clinical trial for our DNA vaccine candidate for COVID-19, INO-4800:

• Across our platform, INOVIO has shown that DNA vaccines and medicines are able to treat and prevent a range of serious and life-threatening diseases related to HPV, cancer and infectious disease. Our DNA medicines are precisely designed DNA plasmids delivered by using INOVIO’s proprietary smart device into the body’s cells to produce a desired T cell and antibody-mediated immune response. DNA medicines are safe and tolerable; they can be quickly designed and manufactured – and unlike other types of vaccines – do not requiring freezing in storage or cold-chain transport.
• Our COVID-19 vaccine candidate, INO-4800, has in its early phases of development, has proven to be safe and tolerable. Peer-reviewed Phase 1 data –published in late 2020 in The Lancet’s EClinicalMedicines – found INO-4800 to be immunogenic in 100% of subjects, including neutralizing antibody and/or T cell responses, with no series adverse events reported.
• Beyond our COVID-19 candidate, INOVIO recently shared OS18 data from our novel combination trial of INO-5401 and INO-9012, which found that at 18 months, that 70% (14/20) of MGMT promoter methylated GBM patients were alive, and 50% (16/32) of MGMT promoter unmethylated patients, which is the more difficult to treat group, were alive after 18 months.

MA: How is a COVID trial different from other trials?

JL: Clinical trials for infectious diseases present similar challenges to the COVID-19 trial, including the inherent challenge of finding a newly infected population with high enough numbers to demonstrate efficacy. Unfortunately, this challenge did not arise for COVID-19, as many people were infected daily in various areas around the world. As a result, many vaccine programs – which traditionally have to wait for seasonality or need to travel to other regions where infection rates are high—were able to demonstrate efficacy in a shorter period of time.

But future COVID-19 vaccine developers will have a more challenging time with recruitment because more people will have access to approved vaccines and more people will be protected as additional vaccine products become available. The hope is that the incidence of infection and severe hospitalizations will decline, and so, as a vaccine developer, I expect to see slower recruitment rates in regions like the US, which contributed significantly to the early COVID-19 vaccine trials. In such cases, vaccinated developers will need to conduct trials in regions with high incidence rates due to low access to approved vaccines.

MA: There are lots of social media groups spreading misinformation about COVID vaccines. What can be done to combat misinformation?

JL: As a scientist and someone who has dedicated her life to pharmaceutical innovation, I can tell you about the important role of vaccines. As a member of the community, I also understand and appreciate that there are a lot of questions, concerns and fear about vaccines. I think there’s great value in a broader dialogue about vaccines to drive both greater awareness, understanding and clarity. [For example, our study plans to partner with community leaders to help us stop the spread of misinformation about COVID-19 vaccines.]

Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.