Lambert Peng is a medical blog writer with a background in pharmaceuticals.
Earlier this month, researchers in China published the results of a clinical study of VV116, a potential new treatment for COVID-19. This article uses plain language to describe what happened in that study. I have also added some of my own commentary at the end.
Why was this study done?
The FDA has currently authorized two medicines, available as a pill, for COVID-19: Paxlovid and molnupiravir. However, both of these medicines have problems. Paxlovid may cause problems when taken together with other medicines. Molnupiravir is not very effective and has a high risk of causing birth defects in unborn babies. Also, the rise of newer COVID-19 variants—such as the omicron variant—has made it urgent for researchers to develop more treatment options.
VV116 is a medicine available in China to help treat COVID-19. It works by blocking a key step in the way COVID-19 replicates. It is a slightly modified version of remdesivir, an injectable medicine that is already sometimes used in the United States for COVID-19. Because it is still being tested, VV116 has not been approved for use by the general public.
What happened during the study?
Researchers in China did an “open,” “prospective cohort” clinical study of VV116 in patients infected with COVID-19. “Open” means that each patient knew whether he or she was being treated with VV116. “Prospective cohort” means that patients were divided into groups, and that whether or not they received VV116 would be based on which group they were in.
Patients were enrolled in the study from March 8, 2022, until March 24, 2022. All participating patients had been hospitalized with the omicron variant of COVID-19. All had to give their consent to participate in the study. They had to be at least 18 years old and test positive for COVID-19 through a PCR test. All patients took regular PCR tests on alternate days starting from the day they were admitted to the hospital.
Not all patients were eligible to participate in the study, for reasons that were previously decided upon by the researchers. Researchers do this to avoid complicating factors that can make it difficult to interpret study results. The reasons for a patient not being eligible to participate in this study included:
- Having severe or critical COVID-19.
- Having low amounts of oxygen in the body, an abnormally high rate of breathing, or an abnormally high heart rate.
- Requiring breathing to be assisted by a mechanical ventilator.
- Having confirmed to be infected by anything else besides COVID-19.
- Having any kind of eye disease.
- Having abnormally high levels of something called “alanine transaminase” or “aspartate transaminase” in the blood. Those two things, if present in high levels in the blood, usually mean that the liver has been damaged.
- Being allergic to any ingredient in VV116.
- Having received any other medicine for treatment of COVID-19.
- Being pregnant or breastfeeding.
- Being part of any other active clinical trial.
Patients were divided into two groups: those who agreed to receive the treatment medicine, and those who refused.
- Those who agreed to receive treatment would take VV116 at a dose of 300 milligrams every 12 hours for 5 days.
- Those who refused would be enrolled into the “control group.”
A control group is used in clinical studies to compare against patients in the treatment group, making it easier to spot differences between the two.
What were the results of the study?
The main result that researchers looked for was how long each patient had “viral shedding” before and after taking VV116. The length of time that a patient had viral shedding was defined as:
- Starting on the first day of having a positive PCR test.
- Ending on the last day of having two consecutive negative PCR tests.
In total, 60 patients received VV116 and 76 patients were put into the control group. In the VV116 group, there were a higher number of patients who had symptoms of COVID-19. (The most common reported symptoms of COVID-19 in both groups were cough and mucus production.) Otherwise, there were no major differences between patients in both groups.
Most of the patients had previously been vaccinated. Among all patients in both groups:
- 11.0% were unvaccinated
- 0.7% were partially vaccinated with one dose
- 45.6% were fully vaccinated with two doses
- 42.6% were vaccinated with a third dose (booster)
Only 3 patients in the VV116 group and 4 patients in the control group had moderate COVID-19. Everyone else had mild COVID-19, and nobody had severe COVID-19. All patients received treatment as needed for symptoms, using common medicines for cough or pain. Nobody received any other antiviral medications, steroids, or antibody treatments.
After all the data had been collected and analyzed, the researchers found out the following:
- In the control group, the viral shedding time was calculated to be 11.13 days.
- In the VV116 group, for patients who received their first dose of VV116 within 5 days of the first positive PCR test, the viral shedding time was calculated to be 8.56 days.
- In the VV116 group, for patients who received their first dose of VV116 more than 5 days from the first positive PCR test, the viral shedding time was calculated to be 11.46 days.
- In the control group, among patients who had symptoms, the viral shedding time was calculated to be 12.25 days.
- In the VV116 group, among patients who had symptoms, the viral shedding time was calculated to be 10.00 days.
Based on this data, the researchers decided that VV116 does shorten viral shedding time in patients who had symptoms. The researchers calculated that VV116 was 2.37 times more effective at shortening viral shedding time in patients if given within 5 days of the first positive PCR test.
Were there any side effects?
The researchers recorded any side effects patients had starting from the day they took their first dose of VV116.
In the VV116 group, 9 patients experienced side effects. None of the patients were considered to have “severe” side effects (side effects that are life threatening or cause permanent damage). The side effects that were reported included the following:
- 7 patients had mildly higher levels of alanine aminotransferase, indirect bilirubin, or bile acid (things which might indicate liver damage) in the blood.
- 1 patient had a higher level of urea (which might indicate kidney damage) in the blood.
- 1 patient had a higher level of white blood cells (which might indicate an infection) in the blood.
All patients with side effects successfully recovered without treatment. None of the patients died during the study.
This article only summarizes the results of one study. Healthcare providers and researchers look at the results of many different studies to decide whether a medicine or treatment is appropriate for patients.
One of the major problems with this study was the setup: It was an open, prospective cohort study. That means it is missing two important things: blinding and randomization.
- Blinding means the patients would take either VV116 or a placebo, and the patients and researchers would not know which one each patient was taking. A placebo is a pill that would have looked like VV116 but did not actually contain any active ingredient. Blinding is important for making sure the results of the study cannot be unfairly influenced by anyone.
- Randomization means the patients would be randomly assigned to receive either VV116 or placebo. This would be done to make the groups more similar, which makes comparing the groups more fair.
For comparison, an early study that was done on molnupiravir (back when it was in the same phase that VV116 is currently in) used both blinding and randomization.
Randomization would have been especially important in this study because the two groups were not similar. The researchers reported that the control group had started out with more symptoms of COVID-19. Therefore, as the study progressed, it is possible that patients of the VV116 group had a better recovery simply because they were less sick to begin with.
This study did not include patients from important population groups, such as children, pregnant women, or patients with severe COVID-19. To be fair, however, the studies that were done on Paxlovid and molnupiravir also did not include most of those groups. Future studies would need to collect data on those populations.
VV116 potentially has a different “place in therapy” compared to Paxlovid or molnupiravir. This means that it will probably be used in a different setting under different circumstances. Paxlovid and molnupiravir were studied in unvaccinated patients who were not yet hospitalized, so their main benefit is to prevent people from being hospitalized due to COVID-19. By contrast, the patients in the VV116 study were mostly vaccinated and already in the hospital. This means that, in the future, VV116 might be used specifically for those patients.
VV116 might be safer to use than Paxlovid or molnupiravir. It does not appear to cause problems when taken together with most other medicines. It is also probably less toxic than molnupiravir to unborn babies.
Overall, VV116 appears to be a safe treatment that can be used in vaccinated and hospitalized patients. But the problems of the current study mean that researchers need more data before it can be approved for use by the general public.
- Link to the original study
An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants
This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.
© 2022 Lambert Peng