Booster Dose Study to Assess the Safety and Immunogenicity of ACM-001 Administered Intramuscularly or Intranasally.
Condition: SARS-CoV-2 Infection
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 1

Summary: 
      An open label, randomized, dose comparison, sequential cohorts study design in healthy
      volunteers (young adults) is a frequently used design in vaccine Phase 1 studies.

      ACM-001 is developed as a booster vaccine against SARS-CoV-2 after a full primary vaccination
      with or without 1-2 booster doses (2 or 3 or 4 doses) schedule with any registered and
      commercial SARS-CoV-2 vaccines.

      The plan is to start with a low dosage of antigen alone, followed by a combination of antigen
      and adjuvant and then to progress to higher dosages to define the safety profile of the
      candidate vaccine as primary endpoint, and its immunogenicity as secondary endpoint.
    

Detailed description: 
      -  Open label, randomized, single dose study.

        -  The ACM-001 vaccine will be evaluated in a single ascending dose (administered IM in 4
           groups of 5 subjects and IN in 4 groups of 5 subjects), which will explore the amount of
           SARS-CoV-2 spike protein derived from strain B.1.351 (5 µg and 15 µg) and adjuvant
           CpG7909 (25 µg and 125 µg) required to provide the optimum immunogenicity and safety, as
           a booster dose in subjects who were previously vaccinated (two, three or four doses)
           against SARS-CoV-2.

        -  Fourty (N=40) healthy adult volunteers aged 18-55 years, will be enrolled and randomized
           in the IN or IM cohorts if they meet eligibility criteria at baseline. Participants who
           benefited from a complete 2 dose-primary vaccination with or without one or two booster
           dose with registered and commercial COVID-19 vaccine(s), at least 3 months prior to
           study vaccination (maximum 5,000 BAU/mL of anti-S Ig), with or without previous
           infection by COVID-19 can be enrolled in this study.

        -  Participants of cohorts 1,3,5 and 7 will receive an IM injection into the deltoid
           region, consisting of 0.4 mL per dose on Day 1. In cohorts 2, 4, 6 and 8, the vaccine
           will be administered IN (2 x 0.2 mL per dose) on Day 1.

        -  Participants will be observed closely in the research unit for at least 2 hours
           following vaccination.

        -  As from Day 30 (following completion of Day 29 visit), subjects may receive an
           additional (3rd or 4th or 5th) commercial SARS-CoV-2 vaccine dose.

        -  All subjects (having received or not a commercial dose of a SARS-CoV-2 vaccine at any
           point of time during their study participation) will be followed up for safety and
           immunogenicity on Day 85 and Day 180 visits.

        -  Solicited local and systemic AEs will be collected for 7 days following the vaccination
           using a daily reactogenicity electronic diary (eDiary). Non-serious unsolicited AEs will
           be collected from administration until 28 days following vaccination. Serious AEs (SAEs)
           and AEs of special interest (AESI; list determined by the Safety Platform for Emergency
           Vaccines (SPEAC; Brighton collaboration)) will be collected throughout the whole 6-month
           study period.

        -  Sentinel dosing will be applied to all cohorts for the early detection of safety
           signals. Two subjects will be dosed ahead of the other volunteers (at least 48 hours),
           with an interval of at least 2 hours between them, to ensure there are no serious acute
           reactions following vaccination. After global evaluation by the Investigator (or the
           responsible physician) and phone contact with the subjects on Day 3, and providing there
           are no safety concerns, the rest of the cohort (N=3) will be dosed.

        -  Seven-day safety data of all subjects (N=10) of a given Ag/CpG dose level will be
           reviewed by an independent data safety monitoring board (DSMB). The interval between the
           last subject receiving his/her vaccine and vaccination of three sentinel subjects with
           the ascending dose levels will be at least 10 days.

        -  On Day 1 (pre-vaccination) and on Days 8 and 29 (28 days post-vaccination), blood
           samples will be drawn for analysis of safety parameters.

        -  At all timepoints, serum and saliva samples will be collected for analysis of the
           humoral immune responses (IgG, IgA and neutralizing antibodies).

        -  The duration of the study for each subject will be approximately 6 months.
    

Intervention name(s): ACM-SARS-CoV-2-beta ACM-CpG vaccine candidate (ACM-001)
Intervention type(s): Biological
Intervention description(s): ACM-SARS-CoV-2-beta ACM-CpG vaccine candidate (ACM-001): Artificial Cell Membranes (ACM) containing recombinant SARS-CoV-2, beta- variant strain, spike protein and ACMs containing CpG adjuvant
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention