Phase I study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

PTX-COVID19-B mRNA vaccine encodes for SARS-CoV-2 Spike protein G614 variant and lacks the proline-proline (986-987 position) mutation present in other COVID-19 vaccines. This Phase 1 observer-blinded, randomized, placebo-controlled, ascending dose study evaluated the safety, tolerability, and immunogenicity of two doses of PTX-COVID19-B vaccine in healthy seronegative adults. Participants received two intramuscular doses, 4 weeks apart, of 16-g, 40-g, or 100-g PTX-COVID19-B. Adverse events were generally mild to moderate, self-resolving, and transient. The most common solicited local and systemic adverse event was pain at the injection site and headache, respectively. After the first immunization, all participants seroconverted, producing high titers of anti-receptor-binding-domain, anti-Spike, and neutralizing antibodies, including neutralizing antibodies against the ancestral viral strain and the Alpha, Beta, and Delta variants of concern, in a dose-dependent way, further increasing over 10-20 times after the second dose. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-g dose showed fewer adverse reactions than the 100-g dose, supporting further investigation of the 40-g dose. Clinical Trial RegistrationClinicalTrials.gov identifier: NCT04765436 (https://clinicaltrials.gov/ct2/show/NCT04765436)

Safety and efficacy of COVID-19 hyperimmune globulin (HIG) solution in the treatment of active COVID-19 infection- Findings from a Prospective, Randomized, Controlled, Multi-Centric Trial

BackgroundCOVID-19 hyper-immune globulin (HIG) solution is a human plasma-derived, highly-purified, concentrated, virus-inactivated preparation of neutralizing antibodies (NAbs) against COVID-19. MethodsThis was a randomized, two-arm, controlled, multi-center trial to evaluate the efficacy and safety of COVID-19 HIG in patients who were hospitalized with moderate-severe COVID-19 infection. ResultsA total of 60 patients were randomized (30 in each arm). Overall, COVID-19 HIG was well-tolerated without any serious treatment-emergent adverse event or tolerability issue. The mean change in ordinal scale by day 8 was 1.7{+/-}1.61 in the test arm vs. 2.0{+/-}1.68 in the control arm (mITT; p=0.367). Early and high NAbs were observed in the test arm compared to the control arm. More patients had negative RT-PCR by day 3 for the test arm vs. the control arm (mITT: 46.67% in test vs. 37.93% in control). The median time to be RT-PCR negative was 5.5 days for the test arm vs. 8.0 days for the control arm for PP population. Patients receiving COVID-19 HIG showed early improvement (reduction) in the biomarkers (CRP, IL-6, and D-dimer). ConclusionCOVID-19 HIG was found to be safe and well-tolerated. Early and high NAbs were achieved in COVID-19 HIG recipients qualifying the product as a suitable treatment option, particularly in an immunocompromised state. It should be given early in infection to mitigate progression to severe disease. It should be evaluated for post-exposure prophylaxis as well as for prevention (where a vaccine is not suitable or effective). It should be evaluated in the pediatric population as well.