The ARCT-154 Self-Amplifying RNA Vaccine Efficacy Study (ARCT-154-01)
Condition: COVID-19 Vaccines
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind study designed to
      evaluate the safety, immunogenicity and efficacy of ARCT-154 in adult participants to be
      enrolled in Vietnam.

      This study consists of four parts:

      Part 1 (Phase 1) will evaluate the safety of the study vaccines in 100 healthy individuals.

      Part 2 (Phase 2) will evaluate the safety and immunogenicity of the study vaccines in 300
      healthy individuals.

      Part 3 (Phase 3a) will evaluate the safety, immunogenicity, and efficacy of the study
      vaccines in 600 individuals with and without underlying medical conditions.

      Part 4 (Phase 3b) will evaluate the safety and efficacy of the study vaccines in 16,000
      individuals with and without underlying medical conditions.

      Part 5 (Phase 3c) will evaluate the safety and non-inferiority in immunogenicity of ARCT-154
      vaccine vs. Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19) in 2400 individuals with and
      without underlying medical conditions.

      In Phase 1, healthy individuals 18 to < 60 years of age will be enrolled. In Phase 2, 3a, and
      3b, individuals 18 years of age and older will be enrolled including individuals with
      underlying medical conditions that put them at higher risk of complications of COVID-19
      disease.

      Phase 1, Phase 2, Phase 3a and Phase 3b participants will be randomly assigned to a study
      group that will receive up to 2 vaccination series. Each vaccination series comprises two
      vaccinations at 28-day intervals: an initial vaccination series with vaccinations on Day 1
      and Day 29 and an additional vaccination series around 2 months after the first series (on
      Day 92 and 120).

      Participants of Phase 2, 3a who received 2 doses of ARCT-154 vaccine will be rerandomized to
      receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus
      placebo on Day 120.

      For Phase 1, Phase 3b and participants in Phase 2 and 3a that received placebo in the first
      vaccination series, the participants will be switched over to the opposite vaccine in the
      second series.

      There is no second vaccination series for Phase 3c as all participants receive active vaccine
      in the initial series.
    

Detailed description: 
      Phase 1 will enroll 100 healthy participants that are randomly assigned 3:1 to receive
      ARCT-154 or placebo (75:25) for the initial series of vaccinations.

      In Phase 2, 300 participants will be randomly assigned 3:1 to receive ARCT-154 or placebo for
      the initial series of vaccinations. Participants that received ARCT-154 in the initial series
      will be rerandomized 3:1 to receive ARCT or placebo on Day 92 followed by placebo on Day 120.

      In Phase 3a, 600 participants will be randomly assigned 3:1 to receive ARCT-154 or placebo
      for the initial series of vaccinations. Participants that received ARCT-154 in the initial
      series will be rerandomized 3:1 to receive ARCT or placebo on Day 92 followed by placebo on
      Day 120.

      In Phase 3b, ~16,000 participants will be randomly assigned 1:1 to receive ARCT-154 or
      placebo for the initial series of vaccinations.

      In Phase 3c, ~2,400 participants will be randomly assigned 1:1 to receive ARCT-154 or Astra
      Zeneca COVID-19 vaccine. Blood samples will be collected and reserved for Immunogenicity
      evaluation for the first 1500 participants (3c-1) and assays for immunogenicity evaluation
      will be performed for the first 800 participants.

      Phase 1 participants must be <60 years of age and healthy. Phase 2, 3a, and 3b and 3c
      participants will include elderly (≥60 years) and those with comorbidities.

      For Phase 2, 3a, 3b and 3c, prior to randomization, participants will be stratified by age (<
      60 or ≥ 60 years of age) and for participants < 60 years of age by risk of severe COVID 19.
      Participants will be followed up for approximately 1 year after completion of the initial
      vaccination series.

      An independent Data and Safety Monitoring Board (DSMB) will perform ongoing review of blinded
      and unblinded data.

      An independent blinded adjudication committee will adjudicate all suspected COVID-19 cases to
      determine if they meet the primary endpoint requirements.
    

Intervention name(s): ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine; Placebo (normal saline); Astra Zeneca COVID-19 vaccine
Intervention type(s): Biological; Other; Biological
Intervention description(s): ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine; Normal saline with the same volume as of ARCT-154; Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19)
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase 1, 2, 3a, 3b: Participants will be randomly assigned to a study group that will receive up to 2 vaccination series. Each vaccination series comprises two vaccinations at 28-day intervals: an initial vaccination series with vaccinations on Day 1 and Day 29 and an additional vaccination series at around 2 months after the first series on Day 92 and 120. Each participant is planned to receive a two-dose vaccination series of ARCT-154 at a dose of 5 µg or a two-dose vaccination series of placebo (saline) in the first series.
Participants in Phase 2, 3a who received 2 doses of ARCT-154 vaccine in the first vaccine series will be rerandomized to receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus placebo on Day 120.
Phase 3c: Participants will be randomly assigned to a study group to receive two-dose vaccination series of ARCT-154 at a dose of 5 µg or approved COVID-19 vaccine comparator (Astra Zeneca's COVID-19 vaccine).
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: ARCT-154; COVID-19; SARS-CoV-2; Immunogenicity; Efficacy