I've mentioned before that my wife is a nurse consultant with NCDHHS. She read a first hand report about the Moderna vaccine trials and I pass it along here.....
Phase I trial:
Recall that Phase I is the safety trial where they are collecting data on initial dosing, safety, whether the vaccine shows signs of doing what they hope it will, and how the body processes the vaccine.
45 healthy 18-55 years old were placed into 3 different dosing categories (25, 100, and 250 mcg) with 2 doses given 28 days apart. 3 participants did not receive the 2nddose: 1 developed hives 5 days after the first injection and 2 others were in isolation due to a COVID exposure after the first shot. There were no fevers reported after the first dose in any group, but fevers were reported after the second dose in the 100 mcg (6/15, 40%) and 250 mcg (8/14, 57%) groups. In addition, muscle aches, headaches, fatigue, chills, and pain and swelling at the injection site were reported. No SARS-COV2 antibodies were detected in any trial participant before the first injection. SARS-COV2 antibodies were detected in half of participants after the first injection and in all participants after the second injection. The lowest immune response was seen in 25 mcg group. Similar immune responses were noted in the 100 and 250 mcg groups. This study showed us that it is important to receive both doses as half of people did not develop any detectable immune response after the first dose. It also showed that the higher dose 250-mcg regimen does not confer additional protection over the 100-mcg regimen, but does likely cause more fevers and other symptoms. There were no major adverse events. This is the kind of data they are looking for in Phase I trials to guide next steps. Additionally, if there are major safety concerns then investigation into the drug may stop here forever.
Here is the reference if you want to read for yourself:
https://www.nejm.org/doi/full/10.1056/NEJMoa2022483While my wife did not develop any symptoms after either shot, this data is very consistent with my personal experience in the Phase III Moderna trial. After the first shot my arm hurt a little bit for about a day and that was all. About 12 hours after the second shot I woke up with chills and a mild fever. I also had some body aches, fatigue, and pain at the injection site. All in all, it was like a minor case of "man flu." The symptoms were mostly alleviated with OTC meds and lasted a little under a day before I felt fine again. The Phase 1a trial suggests that a decent number of people will experience some symptoms, but the rates may change once data is available on more people. I want to be clear; the vaccine DID NOT GIVE ME COVID. It generated an immune response in my body to the Spike protein that was produced. Your immune response and your body fighting off infection is what makes you feel so bad when you are sick. I have since received an antibody test that confirmed that I have COVID19 antibodies against the Spike protein and I would absolutely do it all again, if needed. The available trial data shows that the second shot is very important so the possibility of these types of symptoms needs to be factored in to people's decisions around timing the second shot. It would not have been fun to try and work that next day, but then again, I am a man and we are rarely seen out of bed with any type of symptoms. Pfizer/BioNTech's mRNA vaccine data shows a similar side effect profile and I will detail that in another post.
While the investigator team is blinded to group allotment, it is hard to completely blind the treatment group as to whether they have received vaccine or placebo due to the symptoms that may be produced by the vaccine. It was pretty clear that I had received something. It also seemed likely that my wife was in the placebo arm as she never even developed so much as arm soreness. To me, that makes the recently reported Phase III 95% efficacy data for preventing symptomatic COVID19 disease potentially even more impressive because I feel like, if anything, people would perhaps take on riskier behaviors if they believe they have been vaccinated, resulting in more potential exposures in that group. This is obviously speculative.
Phase 2a trial:
This trial included 600 healthy participants, but the data has not been publicly published as of yet. Recall that in Phase 2 trials the goal is assess for safety, dosing, and development of an immune response. The trial was randomized, blinded, and placebo controlled. Participants were first subdivided by age: 18-55 and 55+. Each age group was then split further by being randomized into either a vaccine or placebo group of either a 50 mcg or 100 mcg dose arm. For example, a 58-year old would be randomized to either the 50 mcg or 100 mcg arm and then randomly receive 2 of those vaccine doses or 2 shots of saline (salt water) 28 days apart.
You can read about the trial design here:
https://l.facebook.com/l.php?u=https%3A%2F%2Fclinicaltrials.gov%2Fct2%2Fshow%2FNCT04405076%3Fterm%3Dmoderna%26cond%3Dcovid-19%26draw%3D2%26fbclid%3DIwAR241MNOZVzgWqSpH9Uqn3U6RWbJddergG_X648wJ8xyG8L1Vt2dH6qcWj8&h=AT0KFD1JDcrvvMh1MhiPUSNlNPZO9D9fKpfQYAR7uTJ5G7uv3cS5Oxwq8efa8sQhiFo_vP0sfRC2LR7L4zfhl0op5KFVZEAJ64rtz2wOQt_RBJLX2C41MQ0Q7A2F2P-aVK5o&__tn__=-UK-y-R&c[0" class="postlink " target="_blank">=AT1-U-5q1Lgc-Ssfr4PvIL304XBZ4JI1ikCiqOdBl0uTY_WPrmrUOxtNbvVBAjLC2kgnZUBRKcifdnwG5EzlaeGLcPaPm5nr7tfENgrJICTUPWHEMIY-nCCOY0QD2eRNX613cGut0YWI6VofJ06eqslGQWUDtLDIIP3f7dyorL1qZ7bY2nlRVUBVtOf6-kBqmqAt5IyPpaxUVOw]
https://clinicaltrials.gov/ct2/show/NCT04405076...Based upon the initial Phase I trial results, they dropped the 250-mcg dose because it caused more adverse effects while not conferring additional immune protection. They also added a 50-mcg dose to see if this would offer similar benefit with even fewer side effects in comparison to the 100-mcg group.
The Phase 3 trial included 30k participants. The researchers chose the 100-mcg dose so one can infer that in the Phase 2a trial the 50-mcg dose did not produce the immune response for which they had hoped. Participants were randomized to either receive 2 x 100 mcg doses or 2 saline placebo shots spaced ~28 days apart. During interim analysis, the following results were reported in a press release: 90 cases of symptomatic COVID19 occurred in the placebo group compared 5 cases in the treatment group. 11 cases of severe COVID19 occurred and were all in the placebo group. There were no significant safety events reported and the rates of side effects reported after the second dose included fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%) and redness at the injection site (2.0%). Fever data was not reported and it is important to note that this was simply a press release that has not been peer-reviewed and that the full data has not been made publicly available at this point.
You can read the press release here:
https://l.facebook.com/l.php?u=https%3A%2F%2Finvestors.modernatx.com%2Fnews-releases%2Fnews-release-details%2Fmodernas-covid-19-vaccine-candidate-meets-its-primary-efficacy%3Ffbclid%3DIwAR15lwxEOxa8c6TYdUwL_cYlTFVjk-qYhysJqREUZdOM3w023JgOjvON1b4&h=AT0A56qqnUtLd8tgCOUInKPnuqz4FnEONKZ4qeTeUh3F5mR5BpAVr9zkD01q6Mb_P7n5jKwbrRPsgRad8uaYLnUOWDN8OZxHwTTa9Z_Mi9rSZgj6vQpHo_UF75OoeIADGydd&__tn__=-UK-y-R&c[0" class="postlink " target="_blank">=AT1-U-5q1Lgc-Ssfr4PvIL304XBZ4JI1ikCiqOdBl0uTY_WPrmrUOxtNbvVBAjLC2kgnZUBRKcifdnwG5EzlaeGLcPaPm5nr7tfENgrJICTUPWHEMIY-nCCOY0QD2eRNX613cGut0YWI6VofJ06eqslGQWUDtLDIIP3f7dyorL1qZ7bY2nlRVUBVtOf6-kBqmqAt5IyPpaxUVOw]
https://investors.modernatx.com/.../modernas-covid-19...As Moderna is applying for EUA, the FDA will be reviewing all of the raw trial data on safety, adverse effects, immunogenicity, and efficacy, in order to make an assessment on whether the vaccine appears efficacious and safe enough to begin administering to additional people outside of a controlled trial setting. The European Union is undertaking a similar process so there will at least be two large, well-established regulatory bodies reviewing this data. These decisions are tough and the timeline has to be balanced against the known threat from COVID19. The FDA timeline of review appears to be about 2 weeks from application/data receipt. My next post will be about the Pfizer/BioNTech mRNA vaccine, which appears to be the initial vaccine offering that will be headed to North Carolina. I sure hope we have some super freezers on standby.
As I have stated in earlier posts: Questions, concerns, and productive discussion are welcome; anti-vaxxer propaganda is not.
Disclaimers: I have no financial conflicts of interest relevant to this topic, other than receiving a small stipend to be a Moderna trial participant like all of the other vaccine trial participants. My real conflict related to this topic is that I may have confirmation bias due to a desire for these vaccines to be safe and to work so that I, along with the rest of my colleagues, can hopefully stop seeing people die from or be physically, emotionally, and financially wrecked by COVID19. These posts are for educational purposes and are reflective of my own interpretation of the medical and scientific literature at this time. Science, by definition, changes with time so these views may change, as well. The views expressed are not representative of the views of my employer and should also not be considered individual medical advice. If you have concerns, you should discuss further with your healthcare clinician.
