Study of the Safety and Immunogenicity of an Intranasal Vaccine for Respiratory Syncytial Virus in Seropositive Children

• ClinicalTrials.gov Identifier: NCT04444284
• Recruitment Status: Active, not recruiting
• First Posted: June 23, 2020
• Last Update Posted: December 11, 2020
• Sponsor: Meissa Vaccines, Inc.
• Information provided by (Responsible Party): Meissa Vaccines, Inc.

Study Description

Brief Summary:

This study evaluates an investigational vaccine that is designed to protect humans against infection with respiratory syncytial virus (RSV) and is administered as drops in the nose. Specifically, the study analyzes the safety of, and the immune response to, the vaccine when administered to healthy children between the ages of 15 and 59 months who are seropositive to RSV.

Condition or disease	Intervention/treatment	Phase
Respiratory Syncytial Virus Infections	Biological: Investigational RSV vaccine MV-012-968 (Dosage 1); Biological: Investigational RSV vaccine MV-012-968 (Dosage 2); Other: Placebo; Biological: Investigational RSV vaccine MV-012-968 (Dosage 3)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: The first 15 enrolled participants will be assigned to Dosage Group 1 and be randomly allocated to receive either investigational vaccine at Dosage 1 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 1 safety data through Day 14, to allow dosage escalation. The next 15 enrolled participants will be assigned to Dosage Group 2 and be randomly allocated to receive investigational vaccine at Dosage 2 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 2 safety data through Day 14, to allow dosage escalation. The final group (Dosage Group 3) will consist of up to 12 enrolled participants who will be allocated to receive investigational vaccine at Dosage 3.
• Masking: Single (Participant)
• Masking Description: The study is single-mask in 2 of the 3 dosage groups: study participants and their parent(s)/guardian(s) will not know their child's study assignment, whereas investigators, site staff, and site pharmacists will remain unmasked.
• Primary Purpose: Prevention
• Official Title: A Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Phase 1b Study to Evaluate the Safety and Immunogenicity of an Intranasal Live Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Seropositive Young Children
• Actual Study Start Date: June 9, 2020
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dosage Group 1: RSV Vaccine Dosage 1; Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 1.	Biological: Investigational RSV vaccine MV-012-968 (Dosage 1); Single dose administered intranasally on Day 1
Placebo Comparator: Dosage Group 1: Placebo; Participants in this arm will receive a single intranasal dose of placebo.	Other: Placebo; Single dose administered intranasally on Day 1
Experimental: Dosage Group 2: RSV Vaccine Dosage 2; Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 2.	Biological: Investigational RSV vaccine MV-012-968 (Dosage 2); Single dose administered intranasally on Day 1
Placebo Comparator: Dosage Group 2: Placebo; Participants in this arm will receive a single intranasal dose of placebo.	Other: Placebo; Single dose administered intranasally on Day 1
Experimental: Dosage Group 3: RSV Vaccine Dosage 3; Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 3.	Biological: Investigational RSV vaccine MV-012-968 (Dosage 3); Single dose administered intranasally on Day 1

Outcome Measures

Primary Outcome Measures :

1. Solicited adverse events (AEs) [ Time Frame: Immediate post-vaccination period ]
   Frequency of solicited AEs will be measured, categorized by severity. Solicited AEs are predefined AEs that may occur after investigational vaccine administration
2. Unsolicited AEs [ Time Frame: Immediate post-vaccination period ]
   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.
3. Serious adverse events (SAEs) [ Time Frame: Full study duration, an average of 6 months ]
   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.
4. Medically attended adverse events (MAEs) [ Time Frame: Full study duration, an average of 6 months ]
   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.

Secondary Outcome Measures :

1. Change in serum RSV-specific neutralizing antibody titers [ Time Frame: Baseline through Day 28, an average of six (6) weeks ]
   Change in serum RSV-specific neutralizing antibody (nAb) titers will be measured per participant.
2. Change in serum binding (RSV F-specific) antibody titers [ Time Frame: Baseline through Day 28, an average of six (6) weeks ]
   Change in serum binding (RSV F-specific) antibody titers will be measured per participant.
3. Change in nasal mucosal binding (RSV F-specific) antibody titers [ Time Frame: Baseline through Day 28, an average of six (6) weeks ]
   Change in mucosal binding (RSV F-specific) antibody titers will be measured per participant.
4. Potential vaccine virus shedding: frequency [ Time Frame: Baseline through Day 28, an average of four (4) weeks ]
   Frequency of any post-vaccination shedding of vaccine virus (as detected by viral culture) will be measured per dosage group and overall.
5. Potential vaccine virus shedding: magnitude [ Time Frame: Baseline through Day 28, an average of four (4) weeks ]
   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.
6. Potential vaccine virus shedding: duration [ Time Frame: Baseline through Day 28, an average of four (4) weeks ]
   If post-vaccination shedding of vaccine virus is detected by culture, duration of shedding (in days) will be measured per dosage group and overall.

Eligibility Criteria

• Ages Eligible for Study: 15 Months to 59 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Key Inclusion Criteria:

1. Children aged 15-59 months
2. Good health based on history, physical examination and medical record review, without evidence or suspicion of chronic disease
3. Seropositive to RSV, as defined by serum neutralizing antibody titer above the threshold described in the study Analytical Plan
4. Written informed consent provided by parent(s)/guardian(s)

Key Exclusion Criteria:

1. Known or suspected chronic illness, particularly cardiopulmonary (including asthma or reactive airways disease), metabolic, hepatic, renal, or infectious (including recurrent or chronic sinusitis)
2. Known or suspected immunodeficiency
3. Household or close contact with anyone ≤ 6 months of age or with immunocompromised individual(s)
4. Nasal obstruction (including due to anatomic/structural causes, acute or chronic rhinosinusitis, or other causes)
5. Receipt of immunoglobulins, monoclonal antibodies and/or any blood products, or ribavirin within 3 months prior to study inoculation, or planned during study period
6. Receipt of an investigational RSV vaccine at any time
7. Any other condition that, in the judgment of the investigator, would be a risk to participant's safety and/or may interfere with study procedures or interpretation of results

Contacts and Locations

Locations

United States, Nebraska

Meridian Clinical Research

Norfolk, Nebraska, United States, 68701

Meridian Clinical Research

Omaha, Nebraska, United States, 68134

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

Meissa Vaccines, Inc.

Investigators

• Study Director: Oliver Medzihradsky, MD MPH MS; Meissa Vaccines, Inc.

More Information

Publications of Results:

Stobart CC, Rostad CA, Ke Z, Dillard RS, Hampton CM, Strauss JD, Yi H, Hotard AL, Meng J, Pickles RJ, Sakamoto K, Lee S, Currier MG, Moin SM, Graham BS, Boukhvalova MS, Gilbert BE, Blanco JC, Piedra PA, Wright ER, Moore ML. A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation. Nat Commun. 2016 Dec 21;7:13916. doi: 10.1038/ncomms13916.

• Responsible Party: Meissa Vaccines, Inc.
• ClinicalTrials.gov Identifier: NCT04444284
• Other Study ID Numbers: MV-005
• First Posted: June 23, 2020
• Last Update Posted: December 11, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Meissa Vaccines, Inc.:

Live attenuated vaccine; Safety; Immunogenicity; Phase 1 clinical trial; Pediatric; Seropositive

Additional relevant MeSH terms:

Respiratory Syncytial Virus Infections; Virus Diseases; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs