Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of RVM-V001 in Healthy Individuals Aged 18-65 Years Previously Vaccinated With BNT162b2 and mRNA-1273
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Infectious Disease
- Sponsor
- RVAC Medicines (US), Inc.
- Enrollment
- 13
- Locations
- 2
- Primary Endpoint
- Changes in safety laboratory parameters from baseline by the Food and Drug Administration (FDA) toxicity grading scale.
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
Phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, and immunogenicity of RVM-V001 administered as a single intramuscular injection in healthy adults. Three dose levels will be evaluated, with progression from low- to high-dose level based on the assessment of safety and tolerability. The study will be conducted at one or more sites in Australia.
Detailed Description
Approximately 54 healthy non-pregnant female and male adults aged 18-65 years inclusive are planned to be enrolled in the study. All subjects will have completed either a 2-dose primary vaccination series with Pfizer Biontech-BNT162b2 SARS-CoV-2 vaccine (P) or Moderna mRNA-1273 (M) (as authorized/approved or as investigational product in a clinical trial), OR have completed the primary series and one homologous booster of Pfizer Biontech-BNT162b2 or mRNA-1273 i.e, P-P-P and M-M-M; the last dose in all cases should have been administered at least 6 months prior to enrollment. This study is composed of 3 dose groups, Groups 1, 2 and 3 per dose level. 18 eligible subjects in each dose group will receive RVM-V001 on Study Day 1 via intramuscular (IM) injection into deltoid muscle of the non-dominant arm. Subjects will be sequentially assigned to a dose group beginning with Group 1 (10 µg RVM-V001) based on the timing of completion of screening. As a precautionary step, 3 sentinel subjects, at least one male and one female will be used within each dose group. Enrollment of each dose group will start with the 3 sentinel subjects. After at least 2 days from the time of study vaccine administration of the 3 sentinel subjects, the 2-day safety data will be collected and reviewed by the principal investigator and local medical monitor. Should there be no safety concerns, the remaining subjects in the same dose group can be enrolled.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female healthy volunteers.
- •Is age 18 and 65 years inclusive on Study Day
- •Judged by the investigator to be healthy based on medical history, physical examination, vital signs, and no significant electrocardiogram (ECG) abnormalities performed at screening.
- •Able to provide informed consent form.
- •Able and willing to comply with all study procedures over follow-up period of approximately 6 months.
- •Have completed either a 2-dose primary vaccination series with Pfizer Biontech-BNT162b2 SARS-CoV-2 vaccine (P) or Moderna mRNA-1273 (M) (as authorized/approved or as investigational product in a clinical trial), OR have completed the primary series and one homologous booster of Pfizer Biontech-BNT162b2 or mRNA-1273 i.e, P-P-P and M-M-M; the last dose in all cases should have been administered at least 6 months prior to enrollment.
- •Body mass index of 18-32 kg/m2, inclusive, at screening.
- •For female subjects with childbearing potential: must agree to avoid pregnancy from 21 days prior to Study Day 1 until at least 90 days after last study vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm.
- •Men must be willing to refrain from sperm donation, starting after screening until 90 days after receiving the last vaccination.
- •Male and female subjects must use a barrier method of contraception, from 21 days prior to Study Day 1 until at least 90 days after last study vaccination. Barrier methods of contraception include:
Exclusion Criteria
- •Documented history of COVID-19 within 6 months prior to enrollment.
- •Positive reverse transcription - polymerase chain reaction (RT-PCR) test for SARS-CoV-2 within 2 days of screening
- •Received any COVID-19 vaccine other than BNT162b2 or mRNA-
- •Received more than 3 doses of any mRNA COVID-19 vaccine.
- •Pregnant or breastfeeding or intending to become pregnant or father children within the projected duration of the trial.
- •Currently working in an occupation with a high risk of exposure to SARS-CoV-2 (eg, Healthcare worker, emergency response personnel having direct interactions with or providing direct care to patients).
- •History of infection of Middle East respiratory syndrome (MERS), or Severe Acute respiratory syndrome (SARS).
- •Positive serology test results for hepatitis C virus antibody, HIV antibody, hepatitis B virus surface antigen at Screening.
- •Currently taking marketed, investigational, off-label product for the prevention of MERS, SARS, or COVID-
- •Is currently participating in or has participated in a study with an investigational product within 30 days preceding Day
Outcomes
Primary Outcomes
Changes in safety laboratory parameters from baseline by the Food and Drug Administration (FDA) toxicity grading scale.
Time Frame: Day 1 to Day 180 post dose
Number of subjects with SAEs, SUSARs, MAAEs and AESIs
Time Frame: Day 1 to Day 180 post dose
GMT of neutralizing antibody (pseudoviral neutralization assay) against Omicron and Delta variants of SARS-CoV-2
Time Frame: Baseline and Day 29
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody
Time Frame: Day 29
Number of subjects with solicited systemic adverse events
Time Frame: Day 1 to Day 8 post dose
Number of subjects with unsolicited adverse events
Time Frame: Day 1 to Day 29 post dose
Seroresponse rate for neutralizing antibody
Time Frame: Day 29
SRR percentage of subjects with ≥4-fold increase of antibody titer over baseline
Seroresponse rate for binding antibodies (IgG) by ELISA
Time Frame: Day 29
SRR percentage of subjects with ≥4-fold increase of antibody titer over baseline
Number of subjects with solicited adverse events
Time Frame: Day 1 to Day 8 post dose
GMT of of neutralizing antibody (pseudoviral neutralization assay) against Wuhan strain
Time Frame: Baseline and Day 29
GMT of serum binding antibodies (IgG) by ELISA
Time Frame: Baseline and Day 29
Geometric Mean Fold Rise (GMFR) of binding antibodies (IgG) by ELISA
Time Frame: Day 29
Secondary Outcomes
- GMT of of neutralizing antibody (pseudoviral neutralization assay) against Wuhan strain(Days 15 and 180)
- Seroresponse rate for neutralizing antibody(Days 15 and 180)
- Geometric Mean Fold Rise (GMFR) of binding antibodies (IgG) by ELISA(Days 15 and 180)
- GMT of serum binding antibodies (IgG) by ELISA(Days 15 and 180)
- Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody(Days 15 and 180)
- GMT of neutralizing antibody (pseudoviral neutralization assay) against Omicron and Delta variants of SARS-CoV-2(Days 15 and 180)
- Seroresponse rate for binding antibodies (IgG) by ELISA(Days 15 and 180)