Safety and Immunogenicity of an Intranasal RSV Vaccine Expressing SARS-CoV-2 Spike Protein (COVID-19 Vaccine) in Adults

Study Overview
=================
Brief Summary
-----------------
This study evaluates an investigational vaccine that is designed to protect humans against infection with SARS-CoV-2, the novel coronavirus causing COVID-19 disease. The investigational vaccine, MV-014-212, is a live attenuated vaccine against respiratory syncytial virus (RSV) that is expressing the spike (S) protein of SARS-CoV-2. MV-014-212 is administered as drops or a spray in the nose. Specifically, this study analyzes the safety of, and the immune response to, the vaccine when administered to healthy adults between the ages of 18 and 69 years who are seronegative to SARS-CoV-2 and have not received a prior vaccine against COVID-19.

Official Title
-----------------
Phase 1, Open-Label, Dose-Escalation Study to Evaluate Tolerability, Safety, and Immunogenicity of an Intranasal Live Attenuated Respiratory Syncytial Virus Vaccine Expressing Spike Protein of SARS-CoV-2 in Healthy Adults Ages 18 - 69 Years

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 1, Single Dose, Intranasal Drops
* Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 2, Single Dose, Intranasal Drops
* Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Single Dose, Intranasal Drops
* Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Two Doses, Intranasal Drops
* Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Single Dose, Intranasal Spray


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adults ≥18 and <56 years (Cohort A) and ≥56 years and <70 years (Cohort B) as determined at the day of signing informed consent SARS-CoV-2 RT-PCR (nasal swab) negative at Day 1 pre-dose Women of childbearing potential (WOCBP) or male subjects with partners who are WOCBP must agree to practice contraception during their study participation from the signing of informed consent for at least 3 months after the final MV-014-212 administration. Written informed consent Exclusion Criteria: Diagnosis of chronic pulmonary disease (e.g. chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, cystic fibrosis). Resolved childhood asthma is not exclusionary. Immunocompromised state due to comorbidities or other conditions as detailed in the study protocol Nasal obstruction (including due to anatomic/structural causes, acute or chronic rhinosinusitis, or other causes) Receipt of any other SARS-CoV-2, other experimental coronavirus, or experimental RSV vaccine at any time prior to the study Healthcare worker, long-term care or nursing home facility resident or employee, member of an emergency response team, or other occupation with high risk of exposure to SARS-CoV-2, and those working outside the home in customer facing occupations (e.g. waiter, cashier or store clerk, public transportation or taxi driver) Positive serum pregnancy test during Screening and/or positive urine pregnancy test on Day 1 Breastfeeding during any period of study participation Occupational or household exposure to children <5 years of age or to immunocompromised persons Receipt of or scheduled to receive any other SARS-CoV-2 vaccine prior to Day 1. Once dosed with MV-014-212, subjects should not receive an authorized or approved COVID-19 vaccine until after the Day 57 visit (single-dose subjects) or the Day 92 visit (two-dose subjects) Any medical disease or condition that, in the opinion of the PI, precludes study participation. This includes acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This study evaluates 3 dosages of MV-014-212 in healthy adults. Cohort A (18-55 years, inclusive) enrolls first. 10 participants (Group 1) receive Dosage 1. 20 participants (Group 2) receive Dosage 2. 50 participants (Group 3) receive Dosage 3: (i) 20 participants (Group 3a) receive a single dose; (ii) 10 participants (Group 3a) receive a 1st dose followed 2nd dose approx. 35 days after the 1st dose; (iii) 20 participants (Group 3b) receive a single dose by nasal atomizer (spray). After review of Cohort A safety data, Cohort B (56-69 years, inclusive) enrolls. Sequential enrollment into Group 4 (10 participants; Dosage 1), Group 5 (20 participants; Dosage 2), then Group 6 (20 participants; Dosage 3) is based in each case on the preceding safety data review, as for Cohort A. Within each group, a sentinel dosing approach is implemented as an added safety measure.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A / Dosage Group 1 (intranasal drops) / Single Dose<br>Participants in this arm (18-55 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 1 in the form of intranasal drops on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 1, Single Dose, Intranasal Drops<br>* Single intranasal dose on Day 1, by intranasal drops<br>|
| Experimental: Cohort A / Dosage Group 2 (intranasal drops) / Single Dose<br>Participants in this arm (18-55 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 2 in the form of intranasal drops on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 2, Single Dose, Intranasal Drops<br>* Single intranasal dose on Day 1, by intranasal drops<br>|
| Experimental: Cohort A / Dosage Group 3a (intranasal drops) / Single Dose<br>Participants in this arm (18-55 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 3 in the form of intranasal drops on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Single Dose, Intranasal Drops<br>* Single intranasal dose on Day 1, by intranasal drops<br>|
| Experimental: Cohort A / Dosage Group 3a (intranasal drops) / Two Doses<br>Participants in this arm (18-55 years) will receive an intranasal dose of the MV-014-212 vaccine at Dosage 3 in the form of intranasal drops on Day 1. These participants will receive a second, identical dose of the MV-014-212 vaccine at Dosage 3 in the form of intranasal drops on Day 36. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Two Doses, Intranasal Drops<br>* Intranasal dose on Day 1 by intranasal drops. Followed by a second, identical dose on Day 36 by intranasal drops<br>|
| Experimental: Cohort A / Dosage Group 3b (intranasal spray) / Single Dose<br>Participants in this arm (18-55 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 3 in the form of a nasal spray on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Single Dose, Intranasal Spray<br>* Single intranasal dose on Day 1, by intranasal spray<br>|
| Experimental: Cohort B / Dosage Group 4 (intranasal drops) / Single Dose<br>Participants in this arm (56-69 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 1 in the form of intranasal drops on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 1, Single Dose, Intranasal Drops<br>* Single intranasal dose on Day 1, by intranasal drops<br>|
| Experimental: Cohort B / Dosage Group 5 (intranasal drops) / Single Dose<br>Participants in this arm (56-69 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 2 in the form of intranasal drops on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 2, Single Dose, Intranasal Drops<br>* Single intranasal dose on Day 1, by intranasal drops<br>|
| Experimental: Cohort B / Dosage Group 6 (intranasal drops) / Single Dose<br>Participants in this arm (56-69 years) will receive a single intranasal dose of the MV-014-212 vaccine at Dosage 3 in the form of intranasal drops on Day 1. | Biological: Investigational vaccine against SARS-CoV-2 [MV-014-212] Dosage 3, Single Dose, Intranasal Drops<br>* Single intranasal dose on Day 1, by intranasal drops<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse events (AEs) | Frequency of solicited AEs will be measured, categorized by severity. Solicited AEs are predefined AEs that may occur after investigational vaccine administration. | Immediate post-vaccination period | 
| Unsolicited AEs | Frequency of unsolicited AEs will be measured, categorized by severity. Unsolicited AEs are any untoward medical occurrences in a participant administered the investigational vaccine, regardless of causal relationship to the investigational vaccine. Unsolicited AEs can include unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of the investigational vaccine. | Immediate post-vaccination period | 
| Serious adverse events (SAEs) | Frequency of SAEs will be measured, categorized by vaccine-relatedness. SAEs are AEs, whether considered causally related to the investigational vaccine or not, that threaten life or result in any of the following: death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect. | Full study duration, an average of 1 year | 
| Medically attended adverse events (MAEs) | Frequency of MAEs will be measured, categorized by vaccine-relatedness. MAEs are AEs, whether considered causally related to the investigational vaccine or not, with unscheduled medically attended visits, such as urgent care visits, acute primary care visits, emergency department visits, or other previously unplanned visits to a medical provider. Scheduled medical visits such as routine physicals, wellness checks, 'check-ups', and vaccinations, are not considered MAEs. | Full study duration, an average of 1 year | 
| Change in serum neutralizing antibody titers against vaccine-encoded SARS-CoV-2 S protein | Change in serum neutralizing antibody (nAb) titers against vaccine-encoded SARS-CoV-2 S protein will be measured per participant | Baseline through Day 29, an average of five (5) weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum binding antibody concentrations against vaccine-encoded SARS-CoV-2 S protein | Change in serum binding antibody concentrations against vaccine-encoded SARS-CoV-2 S protein will be measured per participant | Baseline through Day 29, an average of five (5) weeks | 
| Potential vaccine virus shedding: frequency | Frequency of any post-vaccination shedding of vaccine virus (as detected by viral culture) will be measured per dosage group and overall | Baseline through Day 29, an average of four (4) weeks | 
| Potential vaccine virus shedding: magnitude | If post-vaccination shedding of vaccine virus is detected by culture, peak viral titer (measured in plaque forming units, PFU) will be measured per dosage group and overall | Baseline through Day 29, an average of four (4) weeks | 
| Potential vaccine virus shedding: duration | If post-vaccination shedding of vaccine virus is detected by culture, duration of shedding (in days) will be measured per dosage group and overall | Baseline through Day 29, an average of four (4) weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
live attenuated vaccine, immunogenicity, Phase 1 clinical trial, adult, safety