SARS-CoV2 Infection
Conditions
Brief summary
This is Phase 1 study is to assess tolerability and immunogenicity of three dose levels of the investigational HDT-301 vaccine administered intramuscularly (IM), both in immunization-naïve participants and as a booster for those participants who previously received a SARS-CoV-2 vaccine. Safety and tolerability will be the primary endpoint assessed by incidence of adverse events at each dose through 12 months after completion of the vaccination regimen (either one dose, or two doses provided 56 days apart). Immunogenicity evaluations will be conducted for pre-specified timepoints as secondary and exploratory endpoints.
Detailed description
This is an open-label, dose-ranging, study to evaluate the safety and immunogenicity of the investigational HDT-301 vaccine in healthy (vaccinated or unvaccinated) adult subjects, with a 4:3 recruitment of individual aged 18-49 years and 50-65 years, respectively. The study duration is approximately 13 or 14 months for each subject. Three cohorts of 21 subjects each will be sequentially recruited in the study: 1. Cohort 1 will include individuals with vaccination against COVID-19 who will receive a two-dose schedule of HDT-301 56 days apart. 2. Cohort 2 will include individuals with vaccination against COVID-19 who will receive a one-dose schedule of HDT-301. 3. Cohort 3 will include individuals with no history of vaccination against COVID-19 who will receive a two-dose schedule of HDT-301 56 days apart. Recruiting and screening of participants will be conducted on a continual basis. Subjects confirmed to be Emergency Use Authorization (EUA) SARS-CoV-2 vaccine recipients will first be placed into either Cohort 1 (Study Days 1 and 57; Two-Dose Regimen) or Cohort 2 (Study Day 1; One-Dose Regimen) then subsequently placed into each of the three dose groups. Subjects in the Cohort 3 (naïve, unimmunized) subset will be placed into each of the three dose groups to receive the study vaccine on Study Days 1 and 57 (Two-Dose Regimen). Each cohort will be divided into 3 groups of 7 participants, that will be provided HDT-301 at either a low-, mid- or high-dose. For each of the three-dose groups, a sentinel group will be initially enrolled and followed through Day 8 post-dose one for safety. If no halting rules are met by Day 8 enrollment will proceed to the remaining subjects. Blood samples will be collected during the study for each participant.
Interventions
BIOLOGICALHDT-301
HDT-301 Investigational Vaccine (a Nanoparticle Carrier-Formulated Replicon RNA (repRNA-CoV2S))
Sponsors
Rainier Clinical Research Center
C3 Research Associates
HDT Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
\- Each subject must meet ALL of the following criteria in order to participate in this study: 1. Male or non-pregnant female 18 through 65 years of age at the time of first vaccination. 2. Known clinical and immunization status versus SARS-CoV-2. 1. For Cohort 3 participants this will be either no history of COVID-19 nor reported history of vaccination against COVID-19 by Emergency Use Authorization (EUA) vaccine or investigational product. 2. For Cohort 1 and Cohort 2 participants, this will be verified receipt of investigational or Emergency Use Authorization (EUA) vaccines against SARS-CoV-2 (by provision of either access to medical records, Washington state online vaccine registry, documentation of receipt of investigational vaccine, or Vaccine Card), with most recent vaccination 90 days or more prior to trial initiation (days of immunization will be noted, along with vaccine manufacturer). 3. Understands and agrees to comply with the study procedures and provides written informed consent. 4. In the opinion of the PI or designee, could and would comply with the requirements of the protocol (e.g., completion of Memory Aids, return for follow-up visits, availability for safety calls). 5. Body mass index ≥18.0 and ≤35.0 kg/m2. 6. Considered by the PI or designee to be in good general health as determined by medical history, clinical laboratory assessments, vital sign measurements, and physical examination findings at Screening. 7. Women of childbearing potential1 must agree to use or have practiced true abstinence or use at least one acceptable primary form of contraception. These criteria are applicable to females in a heterosexual relationship and of childbearing potential (i.e., the criteria do not apply to subjects in a same sex relationship). 8. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of and prior to each study vaccination. 9. Must agree to refrain from donating blood or plasma during the study (outside of this study).
Exclusion criteria
\- To participate in this study, all subjects must meet NONE of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Solicited AE | Day 1-71 | Frequency and grade of solicited local and systemic AEs during a 14 day follow-up period after each vaccination (i.e., the day of vaccination and 14 subsequent days). |
| Medically-attended AE, AESI and SAE | Day 1-422 | Occurrence of medically-attended AEs and NOCMCs during the entire study period. Occurrence of AESIs during the entire study period. Occurrence of SAEs during the entire study period. |
| Lab abnormalities | Day 1-85 | Occurrence of any laboratory abnormality (increased or decreased outside normal ranges, as determined by toxicity scales) at 7 and 28 days after each vaccination. |
| Unsolicited AE | Day 1-85 | Frequency and grade of any unsolicited AE within a 28 day period following each vaccination (i.e., the day of vaccination and 28 subsequent days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Endpoints (proportion of IgG responders) | Day 1-85 | Proportion of subjects with a ≥4-fold increase in SARS-CoV-2 B.1.351 Spike-antibody titer from baseline to 28 days after the first (or only) vaccination (Study Day 29) and at 28 days after the second vaccination (Study Day 85), determined by a validated SARS-CoV-2 specific IgG by ELISA. |
| Immunogenicity Endpoints (magnitude of IgG response) | Day 1-85 | Geometric Mean Titer (GMT) of SARS-CoV-2 B.1.351 Spike-specific IgG by ELISA 28 days after the first (or only) vaccination (Study Day 29) and 28 days after the second vaccination (Study Day 85). |
| Immunogenicity Endpoints (magnitude of neutralizing antibodies) | Day 1-85 | Geometric mean titer (GMT) of SARS-CoV-2 B.1.351-specific serum neutralizing antibodies 28 days after the first (or only) vaccination (Study Day 29) and 28 days after the second vaccination (Study Day 85). |
| Immunogenicity Endpoints (proportion responding with neutralizing antibodies) | Day 1-85 | Proportion of subjects with a ≥4-fold increase in SARS-CoV-2 B.1.351-specific serum neutralizing antibody titers from baseline to 28 days after the first (or only) vaccination (Study Day 29; and at 28 days after the second vaccination (Study Day 85). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Immunology (magnitude alternate antibodies) | Day 1-422 | Geometric mean titer (GMT) of SARS-CoV-2 B.1.351 Spike-specific IgM and IgA by ELISA. |
| Exploratory Immunology (proportion with IgG isotype profile) | Day 1-422 | Proportion of subjects with a ≥ 4-fold increase in SARS-CoV-2 B.1.351 Spike-specific IgG1, IgG2, IgG3, and IgG4 ELISA antibody titers from baseline to post-vaccination time points. |
| Exploratory Immunology (response against heterologous Spike) | Day 1-422 | Geometric mean titer (GMT) of IgG binding SARS-CoV-2 Spike of genetic sequences distinct from the vaccine B.1.351 Spike sequence. |
| Exploratory Immunology (T cell phenotype) | Day 1-422 | Diversity of the T cell responses by assessing cells expressing interferon gamma (IFN-γ), interleukin 2 (IL-2), tumor necrosis factor (TNF), and other markers. |
| Exploratory Immunology (proportion with alternate antibodies) | Day 1-422 | Proportion of subjects with a ≥ 4-fold increase in SARS-CoV-2 B.1.351 Spike-specific IgM and IgA antibody titers from baseline to post-vaccination time points. |
| Exploratory Immunology (IgG isotype profile and magnitude) | Day 1-422 | Geometric mean titer (GMT) of SARS-CoV-2 B.1.351 Spike-specific IgG1, IgG2, IgG3, and IgG4 by ELISA. |
Countries
United States
Outcome results
None listed