study of self-amplifying messenger ribonucleic acid (samrna) vaccines against covid-19 in healthy adults and people living with human immunodeficiency virus (hiv)

Conditions: COVID-19; SARS-CoV-2

Summary: the primary objective is to assess the safety and tolerability of samrna vaccines grt-r912, grt-r914, and grt-r918 when administered as prime and/or boost in healthy adult participants naïve to severe acute respiratory syndrome coronavirus 2 (sars-cov-2), sars-cov-2 convalescent, previously vaccinated, or non-vaccinated participants, and people living with hiv (plwh) or hiv-negative.

this phase 1 clinical trial (coral-cepi) will assess the potential of second-generation coronavirus disease 2019 (covid-19) vaccines. these vaccines use a codon optimized spike (s) cassette with additional t cell epitopes (tce) (cassette s-tce) covering multiple epitopes from non-spike proteins to safely drive strong, broad, and durable b cell and t cell immune responses to sars-cov-2. this trial will assess the potential to generate b cell and t cell responses against sars-cov-2 in both people living with hiv (plwh) and hiv-negative participants, in participants who have previously been infected by sars-cov-2, and those who are naive to sars-cov-2, meaning they have neither been infected with nor vaccinated against sars-cov-2. grt-r912, grt-r914, and grt-r918 are vaccines using a samrna vector based and administered as either a single dose or two dose regimen, providing an option for a potent, single-modality approach.

Eligibility criteria:
inclusion criteria: * male or non-pregnant female at least 18 years and no more than 65 years of age at enrollment (parts a, b, and c only). * no previous sars-cov-2 infection or recovered. * hiv-negative status confirmed by laboratory testing. additional inclusion criteria for plwh: * serum positive hiv test or history of hiv infection. * on anti-retroviral therapy for at least 3 months before screening and clinically stable. additional inclusion criteria for part d (grt-r918): * male or non-pregnant female between 18 and \<60 years of age at enrollment. * male or non-pregnant female greater than or equal to 60 years of age at enrollment. * received any authorized sars-cov-2 vaccine series at least 2 months prior to study vaccine. exclusion criteria: * current active infection with covid-19. * positive for sars-cov-2 by nasal swab polymerase chain reaction (pcr) at screening. * currently receiving treatment or prevention agents with activity against sars-cov-2. * breastfeeding, pregnant, or planning to become pregnant during the course of the study. * received or plans to receive any non-study provided sars-cov-2 vaccine (including boost) during the study period (except for part d). * received or plans to receive any live, attenuated vaccine within 28 days before or after study vaccination. * received or plans to receive any subunit or killed vaccine within 14 days before or after vaccination. * received or plans to receive immunoglobulins and/or any blood products within the 3 months preceding the planned administration of first study vaccination or at any time during the study. * currently active viral infection of hepatitis b virus or hepatitis c virus. additional exclusion criteria for plwh: * screening cd4+ t cell count ≤200 cells/mcl. * viral load ≥10,000 virus particles/ml. * history of opportunistic illness indicative of stage 3 hiv infection. * acute febrile illness within 4 weeks before the first vaccination. additional exclusion criterion for part d (grt-r918) cohorts d3, d4, d7, and d8: - received last dose of any authorized sars-cov-2 vaccine series within 2 months prior to study vaccine.

Keywords: sars-cov-2 vaccine coronavirus disease (covid-19) self-amplifying mrna (samrna) human immunodeficiency virus (hiv)