Phase 3 Trial Data for the Moderna COVID-19 Vaccine

In this phase 3 trial, the ability of the Moderna COVID-19 vaccine booster injection dose to produce antibodies against COVID-19 spike protein was tested in participants aged 18 years or older.¹ Safety data was also tracked. The study took place in the United States. A total of 171 participants enrolled, and all of them had previously received two primary series injections of 100 micrograms of mRNA each in the original phase 3 study. All participants received the booster injection at a dose of 50 micrograms of mRNA. The booster injection was given at least 6 months after the second primary series injection. There was no placebo group.

The gender breakdown was 61% female and 39% male. The average age was 52 years. The racial/ethnic breakdown was 96% white; 6% Hispanic/Latino/Latina; 3% Black/African-American; 1% Asian; 1% Native American or Alaskan Native. 

The booster injection was very effective at provoking an antibody response to COVID-19 spike protein. The average antibody level 28 days after the booster injection was 70% higher than the average antibody level seen 28 days after the second vaccine injection in the original phase 3 trial. In laboratory tests, participants’ antibodies were effective against the Delta variant of the virus. The rise in antibodies was seen for both younger and older participants. 

The most common side effects were pain at the injection site (84% of participants), fatigue (59%), headache (55%), muscle pain (49%), joint pain (41%), chills (35%), swollen lymph nodes in the armpit (20%), nausea/vomiting (11%), fever (7%), swelling in the injection arm (5%), and redness in the injection arm (5%). There were no serious adverse events related to the booster injection. There were no deaths. 

Further studies are ongoing to test the effectiveness of the booster dose for preventing COVID-19 illness. 

Primary Series (Two-Dose Injection) Original Phase 3 Safety/Effectiveness Trial for Ages 18+ 

In this phase 3 trial, the safety and effectiveness of the Moderna COVID-19 vaccine administered in two 100 µg doses 28 days apart was compared with placebo injection (salt water) in adults 18 years of age and older.²The study took place in 99 sites in the United States. 

A total of 15,181 participants received the vaccine, and 15,170 received the placebo. The gender breakdown was 47.3% female and 52.7% male. The median age was 51.4 years, with the youngest participant being 18 years old and the oldest being 95 years old. The racial/ethnic breakdown was 79.2% white; 20.5% Hispanic/Latino/Latina; 10.2% Black/African-American; 4.6% Asian; 0.8% Native American or Alaskan Native; 0.2% Native Hawaiian or Pacific Islander; 2.1% were multiracial; and 3.0% were unknown, other, or did not report. A high-risk chronic condition for severe COVID-19 was present in 22.3% of participants, and 4% of participants had 2 or more high-risk conditions. The high-risk conditions included diabetes (9.4% of the study population), obesity with a body mass index of 40 or higher (6.7%), significant cardiac disease (4.9%), chronic lung disease (4.8%), HIV positive status (0.6%), and liver disease (0.6%). 

The definition for a “confirmed COVID-19 case” that the investigators used in this study was the presence of at least one respiratory COVID-19 symptom OR 2 system-wide symptoms (fever, chills, body aches, etc.) combined with a positive SARS-COV-2 test by PCR (“molecular test”). 

The vaccine was very effective for the prevention of symptomatic COVID-19 disease in this study. In the vaccine group, there were 11 cases of confirmed COVID-19 disease that happened 14 days or later after the second dose of vaccine. In the placebo group, there were 185 cases of confirmed COVID-19 disease that happened 14 days or later after the second “dose” of placebo. This corresponds to 94.1% vaccine efficacy. The authors looked at the vaccine efficacy among subgroups defined by age, sex, race and ethnicity, and presence of one or more risk factors for severe COVID-19. The efficacy rate was between 86.4% and 97.5% for these various subgroups.

The researchers also looked at severe COVID-19 disease. Thirty participants had severe COVID-19 disease at least 14 days after the second injection. All of these were in the placebo group. Nine of the severe cases required the participant to be hospitalized. One participant with severe COVID-19 died of the disease (a 54-year-old with diabetes). 

Side effects were more common after the second injection. They were also more common in younger participants (18 years to 64 years) than in older participants (64 years and over). The information below about pain, redness, and swelling is about the second injection in younger participants, because that is when the highest number of side effects happened. The most common side effect reported was pain at the injection site in the arm, by 89.9% of the vaccine group and 18.7% of the placebo group. The pain was generally mild to moderate and lasted 2-3 days, although 3.2% of the vaccine group and 1.7% of the placebo group reported the pain as severe. Redness at the injection site was reported by 4.6% of the vaccine group and 0.2% of the placebo group. Swelling at the injection site was reported by 12.6% of the vaccine group and 0.3% of the placebo group. Swollen glands in the armpit of the injection arm were reported by 16.2% of the vaccine group and 4.3% of the placebo group. 

Other side effects were fever, chills, headache, fatigue and body aches. These were more common after the second injection, rather than the first, and were more common in younger participants than in older participants. These effects usually lasted 1 to 5 days and were managed with over-the-counter pain relievers/fever reducers. The information below is about these side effects after the second injection in younger participants: fever (17.4% of the vaccine group and 0.4% of the placebo group); fatigue (67.6% and 24.6%); headache (62.8% and 25.3%); chills (48.6% and 6.0%); joint pain (45.5% and 10.7%); nausea/vomiting (21.4% and 7.3%). While side effects were generally mild to moderate, 0.5% of participants in the vaccine group and 0.2% of participants in the placebo group reported their side effects as severe. 

There were 10 serious adverse events that may have been caused by the vaccine injection (6 events) or the placebo injection (4 events).  In the vaccine group, the following were reported by one patient each: autonomic nervous system imbalance (dysfunction of the nerves that control heart rate and blood pressure); serious shortness of breath; serious nausea; serious vomiting; serious flare-up of rheumatoid arthritis; and serious swelling of the legs. Two patients reported serious facial swelling. In the placebo group, one patient each experienced the following: serious pins and needles feeling in the limbs; pulmonary embolism (blood clot in the lungs); polymyalgia rheumatica (a muscle pain disorder); serious swelling of the face; serious feeling of being hot; a serious anxiety reaction; and a serious bleeding episode. There were no deaths that were associated with the vaccine or placebo injection.