- Amid concerns among Americans that the rush to approve COVID-19 vaccines may lead to corner-cutting and end products that are not up to typical FDA efficacy standards, leading developers Moderna (NASDAQ:MRNA) and Pfizer (NYSE:PFE) have taken the unusual steps of publishing the protocols of the large-scale late-stage trials for their respective candidates.
- Moderna's Phase 3 trial of mRNA-1273, two 100 microgram doses 28 days apart, will recruit ~30K adults, 60-75% younger than 65 years old not at risk for complications and 25-40% at least 65 years old (the single most significant risk factor) or less than 65 at increased risk of COVID-19 complications.
- The primary efficacy endpoint is the incidence of first-occurrence COVID-19 cases starting 14 days after the second shot.
- A confirmed (via molecular test) COVID-19 case is defined as a participant who has experienced at least TWO of the following symptoms: fever (≥ 38ºC), chills, myalgia (muscle soreness), headache, sore throat, new olfactory and taste disorder(s) OR he/she must have experienced at least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing OR clinical or radiographic evidence of pneumonia.
- Pfizer and BioNTech's (NASDAQ:BNTX) Phase 3 study of BNT162b2, two 30 microgram doses 21 days apart, will recruit 30K adults stratified in two groups: 16-55 years old and 55+.
- The primary efficacy endpoint is the incidence of confirmed COVID-19 cases starting 7 days after the second shot as measured by the number of cases per 1,000 person-years of follow-up.
- A confirmed (via molecular test) COVID-19 case is defined as participants experiencing at least ONE of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased myalgia (muscle soreness), new loss of taste or smell, sore throat, diarrhea or vomiting.
- Moderna's criteria are a more restrictive and could potentially show a higher efficacy rate for mRNA-1273 as a result.
- The number of COVID-19 cases in people who just reported one symptom is unknown. According to a July report from CDC, almost all (96%) of infected persons reported "at least" one symptom of fever, cough or shortness of breath according to case investigation forms while 31% reported all three. Based on these percentages, the proportion of people reporting only one symptom could lead to a material difference in the efficacy of the two vaccines.
- The most common symptoms are cough (50%), fever (43%), muscle soreness (36%), headache (34%), shortness of breath (dyspnea) (29%), sore throat (20%), diarrhea (19%), nausea/vomiting (12%) and loss of taste/smell (10% each) according to the CDC.
- The incidence of severe COVID-19 cases is a secondary endpoint in both trials. Both companies appear to have the similar criteria (aside from their base definitions): Confirmed COVID-19 infection as specified above plus any of the following: clinical signs indicative of severe systemic illness, respiratory rate ≥ 30 per minute, heart rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 < 300 mm Hg OR respiratory failure or acute respiratory distress syndrome (ARDS), (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or extracorporeal membrane oxygen), evidence of shock (systolic blood pressure < 90 mmHg, diastolic BP < 60 mmHg or requiring vasopressors), OR significant acute renal, hepatic or neurologic dysfunction, OR admission to an intensive care unit or death.
- Pfizer will measure the incidence of severe cases as the number per 1,000 patient-years of follow-up.