Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals

Phase 1b, Randomized, Open-label Study to Evaluate the Safety, Tolerability, and Immunogenicity of RVM-V001 Only, RVM-V002 Only, or RVM V001 + RVM V002 (Co Administered as Separate Injections) in Healthy Adults Previously Vaccinated With an Inactivated Virus or mRNA-based COVID-19 Vaccine in Singapore

Phase 1b, randomized, open-label, study to evaluate the safety, tolerability, and immunogenicity of RVM-V001 only, RVM-V002 only, or RVM V001 + RVM V002 (Co administered as Separate Injections) in healthy adults. The study will be conducted at one site in Singapore.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Infectious Disease
• Intervention / Treatment: Biological: RVM-V001 30 µg; Biological: RVM-V001 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration

Detailed Description

A total of 48 healthy men and non-pregnant women aged 21 years and older will be stratified by prior vaccination. Twenty-four subjects who have received a 3 dose primary vaccination series, with or without 1 booster dose, of an approved inactivated virus vaccine (BBIBP-CorV or CoronaVac) will be randomized at a 1:1:1 ratio to receive RVM V001 (30 µg) only, RVM V002 (30 µg) only, or RVM-V001 (15 µg) + RVM V002 (15ug).

An additional 24 subjects who have received 3 doses (primary vaccination series and 1 booster dose) of an mRNA vaccine (BNT162b2) will be randomized at 1:1:1 ratio to receive RVM-V001 (30 µg) only, RVM V002 (30 µg) only, or RVM-V001 (15 µg ) + RVM V002 (15 µg ). The last dose of the prior vaccination should have been administered at least 6 months prior to enrolment in this study. For administration of RVM V001 only or RVM V002 only, subjects will receive a single dose of RVM-V001 or RMV-V002 vaccine on Day 1 via intramuscular (IM) injection into deltoid muscle, preferably of the non-dominant arm.

For the RVM V001 + RVM V002 administration, subjects will receive a single dose of RVM-V001 in the left arm deltoid muscle and then followed immediately with a single dose of RVM-V002 in the right arm deltoid muscle.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 308443
    • P.H. Feng Research Centre, NCID,TTSH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female healthy volunteers.
• Aged 21 years and older on Day 1
• Judged by the investigator to be healthy based on medical history, physical examination, and vital signs evaluation at Screening visit.
• Able to provide informed consent form.
• Able and willing to comply with all study procedures over follow-up period of approximately 6 months.
• Have documented completion of a 2-dose primary vaccination series and 1 booster vaccination with BNT162b2 OR a 3-dose primary vaccination series, with or without 1 booster dose, with an approved inactivated virus vaccine (BBIBP-CorV or CoronaVac). The last dose in all cases should have been administered at least 6 months prior to enrolment in this study.
• For female subjects with childbearing potential: must agree to avoid pregnancy from 21 days prior to Day 1 until at least 90 days after the 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.

Exclusion Criteria:

• Received any COVID-19 vaccine other than BNT162b2, BBIBP-CorV, or CoronaVac.
• Received more than 3 doses of BNT162b2 or more than 4 doses of BBIBP-CorV or CoronaVac.
• Women who are pregnant or breastfeeding or intending to become pregnant; mend who will father children within the projected duration of the trial.
• Positive serology test results for hepatitis C virus antibody, human immunodeficiency virus antibody, or hepatitis B viral surface antigen at Screening.
• Is currently participating in or has participated in a study with an investigational product within 30 days preceding Day 1.
• History of severe allergic reactions (eg, acute anaphylaxis, urticaria, skin eczema, dyspnoea, angioneurotic oedema) or other significant adverse reactions to COVID19 vaccines; allergy to known composition of RVM-001 and RVM-002.
• History of coagulation dysfunction (eg, coagulation factor deficiency, coagulation disease).
• Vaccinated with live attenuated vaccine within 1 month, or any other vaccine within 14 days, of Day 1 vaccination.
• Received systemic immunosuppressants within 4 months prior to vaccination or an anticipated need for immunosuppressants at any time during the study. Topical or inhaled treatment is allowed if not used within 14 days prior to Day 1 vaccination.
• Received blood products within 3 months prior to Day 1 vaccination.
• History of alcohol or drug abuse within 3 years prior to Day 1 vaccination.
• Fever (temperature > 37.5°C), dry cough, fatigue, nasal obstruction, runny nose, sore throat, myalgia, diarrhoea, shortness of breath, or dyspnoea on the day of vaccination.
• Any condition that, in the opinion of the investigator, would pose a health risk to the subject if enrolled, could interfere with the evaluation of the study vaccine, or interfere with interpretation of the study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RVM-V001 30 µg -BNT162b2 subjects; RVM-V001-30 µg administered as a single dose of by intramuscular injection on Day 1 on BNT162b2 subjects	Biological: RVM-V001 30 µg; For BNT162b2 subjects; Biological: RVM-V001 30 µg; For BBIBP-CorV or CoronaVac subjects
Experimental: RVM-V002 30 µg -BNT162b2 subjects; RVM-V001-30 µg administered as a single dose of by intramuscular injection on Day 1 on BNT162b2 subjects	Biological: RVM-V002 30 µg; For BNT162b2 subjects; Biological: RVM-V002 30 µg; For BBIBP-CorV or CoronaVac subjects
Experimental: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration -BNT162b2 subjects; RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; a single dose of RVM-V001 in the left arm deltoid muscle and then followed immediately with a single dose of RVM-V002 in the right arm deltoid muscle on Day 1 on BNT162b2 subjects	Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; For BNT162b2 subjects; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; For BBIBP-CorV or CoronaVac subjects
Experimental: RVM-V001 30 µg; RVM-V001-30 µg administered as a single dose of by intramuscular injection on Day 1 on BBIBP-CorV or CoronaVac subjects	Biological: RVM-V001 30 µg; For BNT162b2 subjects; Biological: RVM-V001 30 µg; For BBIBP-CorV or CoronaVac subjects
Experimental: RVM-V002-30 µg; RVM-V002-30 µg administered as a single dose of by intramuscular injection on Day 1 on BBIBP-CorV or CoronaVac subjects	Biological: RVM-V002 30 µg; For BNT162b2 subjects; Biological: RVM-V002 30 µg; For BBIBP-CorV or CoronaVac subjects
Experimental: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; a single dose of RVM-V001 in the left arm deltoid muscle and then followed immediately with a single dose of RVM-V002 in the right arm deltoid muscle on Day 1 on BBIBP-CorV or CoronaVac subjects	Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; For BNT162b2 subjects; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration; For BBIBP-CorV or CoronaVac subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety in terms of solicited adverse events	Number of subjects with solicited adverse events	Day 1 to Day 7 inclusive
Safety in terms of solicited systemic adverse events	Number of subjects with solicited systemic adverse events	Day 1 to Day 7 inclusive
Safety in terms of unsolicited adverse events	Number of subjects with unsolicited adverse events	Day 1 to Day 28 inclusive
Safety in terms of SAEs, SUSARs, MAAEs and AESIs	Number of subjects with SAEs, SUSARs, MAAEs and AESIs	Day 1 to Day 180 post dose
Safety in terms of laboratory-based AEs	Changes in safety laboratory parameters from baseline by the Food and Drug Administration (FDA) toxicity grading scale.	Day 1 to Day 180 post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity in terms of Nab	GMT of neutralizing antibody (pseudoviral neutralization assay) against Wuhan strain and BA.1 subvariant	Days 1,8,15,29 and 180
GMT of neutralizing antibody (pseudoviral neutralization assay) against Variants of Immunogenicity in terms of Nab	GMT of neutralizing antibody (pseudoviral neutralization assay) against Variants of concerns of SARS-CoV-2	Days 1,8,15,29 and 180
Immunogenicity in terms of Humoral immune response by ELISA	GMT of serum binding antibodies (IgG) by ELISA	Days 1,8,15,29 and 180
Seroresponse rate for neutralizing antibody	SRR percentage of subjects with ≥4-fold increase of antibody titer over baseline	Days 8,15,29 and 180
Seroresponse rate for binding antibodies (IgG) by ELISA	SRR percentage of subjects with ≥4-fold increase of antibody titer over baseline	Days 8,15,29 and 180
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody		Days 8,15,29 and 180
Geometric Mean Fold Rise (GMFR) of binding antibodies (IgG) by ELISA		Days 8,15,29 and 180

Collaborators and Investigators

• Sponsor: RVAC Medicines (US), Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Actual): September 21, 2023
• Study Completion (Actual): September 21, 2023

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: RV003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No