A Phase 2 Randomized Multisite Trial to Inform Public Health Strategies Involving the Use of MVA-BN Vaccine for Mpox

Study Overview
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Brief Summary
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This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two ID regimens for MVA-BN vaccine compared to the standard SC regimen in healthy, vaccinia-naïve adults 18 to 50 years of age, inclusive, (Stage 1). In Stage 2 of the study, the standard SC regimen will be evaluated in adolescents ages 12 through 17 years, inclusive, and compared to the standard SC regimen in adults ages 18 to 50, inclusive. In Stage 2, approximately 210 healthy, vaccinia-naïve adults will be enrolled in a comparator arm (Arm 4) and will be given the standard, licensed regimen of 1x10^8 MVA-BN administered SC on Day 1 and 29 and will be combined with adults from Arm 3 (Stage 1) to be the comparator for the primary endpoint, non-inferiority testing. Approximately 210 healthy, vaccinia-naïve adolescents will be enrolled and given 1x10^8 MVA-BN administered SC on Days 1 and 29 (Arm 5). The study will have a set target enrollment of at least 25% adolescents ages 12 to 14 years to ensure that adequate numbers of younger adolescents are enrolled. The primary objectives are 1.) To determine if peak humoral immune responses in adults ages 18-50 years following an ID regimen of 2 x 10^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10^8 TCID50 MVA-BN administered SC; 2.) To determine if peak humoral immune responses in adults ages 18-50 years following an ID regimen of 1 x 10^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10^8 TCID50 MVA-BN administered SC.

Detailed Description
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This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two ID regimens for MVA-BN vaccine compared to the standard SC regimen in healthy, vaccinia-naïve adults 18 to 50 years of age, inclusive, (Stage 1). In Stage 2 of the study, the standard SC regimen will be evaluated in adolescents ages 12 through 17 years, inclusive, and compared to the standard SC regimen in adults ages 18 to 50, inclusive. In Stage 1, approximately 230 adult participants will be enrolled and randomized to one of three study arms. The two dose sparing strategies include one-fifth (2 x 10^7) and one-tenth (1 x 10^7) of the standard dose of MVA-BN administered ID on Day 1 and 29 (Arm 1 and 2, respectively). The comparator arm (Arm 3) will be the 2-dose standard (1 x 10^8) MVA-BN SC regimen. Stage 1 will enroll a 1:1:1 randomization allocation. In Stage 2, approximately 210 healthy, vaccinia-naïve adults will be enrolled in a comparator arm (Arm 4) and will be given the standard, licensed regimen of 1x10^8 MVA-BN administered SC on Day 1 and 29 and will be combined with adults from Arm 3 (Stage 1) to be the comparator for the primary endpoint, non-inferiority testing. Approximately 210 healthy, vaccinia-naïve adolescents will be enrolled and given1x10^8 MVA-BN administered SC on Days 1 and 29 (Arm 5). The study will have a set target enrollment of at least 25% adolescents ages 12 to 14 years to ensure that adequate numbers of younger adolescents are enrolled. The primary objectives are 1.) To determine if peak humoral immune responses in adults ages 18-50 years following an ID regimen of 2 x 10^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10^8 TCID50 MVA-BN administered SC; 2.) To determine if peak humoral immune responses in adults ages 18-50 years following an ID regimen of 1 x 10^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10^8 TCID50 MVA-BN administered SC. The Secondary Objectives are 1.) To determine if peak humoral immune responses in adolescents ages 12 to 17 years following administration of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC are non-inferior to the response in adults ages 18 to 50 years who received the licensed 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN; 2.) To describe safety of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years

Official Title
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A Phase 2 Randomized, Open-Label, Multisite Trial to Inform Public Health Strategies Involving the Use of MVA-BN Vaccine for Mpox

Conditions
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Monkeypox

Intervention / Treatment
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* Biological: JYNNEOS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals 18 - 50 years of age inclusive at the time of consent; OR Adolescent ages 12 to 17 years inclusive at the time of consent. Adult participant is able to read the written informed consent, states willingness to comply with all study procedures and is anticipated to be available for all study visits; OR Parent(s)/Legal Authorized Representative (LAR)(s) of the participating adolescent is able to read and provides written informed permission and participating adolescent provides assent as appropriate for age or development and approved by IRB. Adolescent states willingness to comply with all study procedures and is anticipated to be available for all study visits. . Adult participant is able to understand and agrees to adhere to Lifestyle Considerations during the study; OR Parent(s)/LAR(s) of the participating adolescent is able to understand and states willingness to comply with Lifestyle Considerations. Females of reproductive potential who have sexual intercourse with males must agree to use highly effective contraception for at least 1 month prior to signing ICF and through Day 57. NOTE: See MOP for definitions and list of acceptable and highly effective methods of contraception In good general health as evidenced by medical history, physical examination, and clinical judgement of the investigator to be in stable state of health. NOTE: Participants with pre-existing stable chronic medical conditions defined as conditions not requiring significant change in therapy or hospitalization for worsening disease in the 4 weeks prior to enrollment can be included at the discretion of the investigator. This includes stable, well-controlled HIV positive individuals. Individuals with HIV must be on suppressive ART for at least 6 months, report a CD4 count of greater than 350 cells/µL and no AIDS-defining illness in the last year. Exclusion Criteria: Ever received a licensed or an investigational smallpox or monkeypox vaccine. *This includes Dryvax, Acam2000, LC 16 m8, MVA-based vaccine candidate or licensed vaccines, and Jynneos, Imvamune or Imvanex) Any history of monkeypox, cowpox, or vaccinia infection. Close contact of anyone known to have monkeypox in the 3 weeks prior to signing ICF Immunocompromised as determined by the investigator Recent or current use of any immunosuppressing medications in the 4 weeks prior to signing ICF. **Topical, ophthalmic, inhaled, intranasal and intraarticular corticosteroids are acceptable, but receipt of >/=20 mg/day of prednisone or equivalent for >/=14 consecutive days in the 4 weeks prior to signing ICF is exclusionary. Pregnant or breast feeding. Received or plans to receive a live vaccine or any COVID-19 vaccine in the 4 weeks before or after each study vaccination. Received or plans to receive any other vaccine in the one week before or after each study vaccination. Received experimental therapeutic agent or vaccine in the 3 months prior to signing ICF. Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products. ***This includes individuals with history of severe allergic reaction to gentamicin, ciprofloxacin, chicken or egg protein. Has tattoos, scars, or other marks which would, in the opinion of the investigator, interfere with assessment of the vaccination site. Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes study participation. ****This includes acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial. Adolescent or adult participant has a history of myocarditis/pericarditis or a history of structural congenital heart defect/cardiac dysrhythmia that, in the opinion of the investigator, poses increased risk to the participant. Adolescent or adult participant has a history of COVID-19 (with positive test for SARS-CoV-2) in the 4 weeks prior to receipt of the first study vaccination. Note: This includes positive rapid antigen test, polymerase chain reaction (PCR) assay, or other nucleic acid amplification (NAAT) test including those performed by the participant at home.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 4<br>0.5 mL of 1 x 10^8 (50% Tissue Culture Infectious Dose (TCID50) JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN)) administered subcutaneously on adults ages 18-50 years on Days 1 and 29. N=135 | Biological: JYNNEOS<br>* JYNNEOS is FDA-approved and licensed as a smallpox and monkeypox vaccine in the United States. JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus.<br>|
| Experimental: 5<br>0.5 mL of 1 x 10^8 (50% Tissue Culture Infectious Dose (TCID50) JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN)) administered subcutaneously on adolescents ages 12-17 years on Days 1 and 29. N=315 | Biological: JYNNEOS<br>* JYNNEOS is FDA-approved and licensed as a smallpox and monkeypox vaccine in the United States. JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) in adolescents and adults. | To determine if peak humoral immune responses in adolescents ages 12 to 17 years are non-inferior to adults after receipt of a 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN. | Day 43 | 
| Occurrence of Adverse Events of Special Interest (AESI) in adolescents. | Frequency and description of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years. | Day 1 through Day 210 | 
| Occurrence of Medically Attended Adverse Events (MAAE) in adolescents. | Frequency and description of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC | Day 1 through Day 210 | 
| Occurrence of Serious Adverse Events (SAEs) in adolescents. | Frequency and relatedness of serious Adverse Events (SAE) of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in for the duration of the study. | Day 1 through Day 394 | 
| Occurrence of solicited Adverse Events (AE) in adolescents. | Frequency and severity of solicited systemic and local Adverse Events for 7 days after each vaccination of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years. | Day 1 through Day 36 | 
| Occurrence of unsolicited Adverse Events (AE) in adolescents. | Frequency severity, and relatedness of unsolicited Adverse Events after each vaccination of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in for adolescents ages 12 to 17 years. | Day 1 through Day 57 | 
| Occurrence of withdrawals and discontinuations of vaccination in adolescents. | Frequency of occurrence within adolescents ages 12 to 17 years | Day 1 through Day 394 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) in adolescents and adults | For adolescents ages 12 to 17 years compared to adults at baseline, prior to the second vaccination, and following receipt of the 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN. | Day 1 through Day 394 | 
| Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) in adolescents and adults | Seroconversion in adolescent study arms 1-5 | Day 1 through Day 394 | 
| Frequency of withdrawals or discontinuation of vaccination in adolescents and adults | Frequency in study arms 1-5 | Day 1 through Day 181 | 
| Occurrence of Adverse Events of Special Interest (AESI) in adolescents and adults | In study arms 1-5 | Day 1 through day 210 | 
| Occurrence of Medically Attended Events (MAAE) in adolescents and adults | Frequency and description in study arms 1-5. | Day 1 through Day 210 | 
| Occurrence of Medically Attended Events (MAAE) in adolescents and adults | Frequency and relatedness in study arms 1-5 | Day 1 through Day 210 | 
| Occurrence of Serious Adverse Events (SAE) in adolescents and adults | Frequency and relatedness in study arms 1-5 | Day 1 through Day 181 | 
| Occurrence of Serious Adverse Events (SAE) in adolescents and adults | Frequency and relatedness in study arms 1-5 | Day 1 through Day 394 | 
| Occurrence of solicited Adverse Events (AE) for 7 days after each vaccination in adolescents and adults | Frequency, severity, and relatedness of solicited systemic and local Adverse Events for 7 days after each vaccination in study arms 1-5. | Day 1 through Day 36 | 
| Occurrence of unsolicited Adverse Events (AE) in adolescents and adults | Frequency, severity, and relatedness of unsolicited Adverse Events for 28 days after each vaccination; in study arms 1-5. | Day 1 through Day 57 | 
| Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) half-life (t ½) in adolescents and adults. | For adolescents ages 12 to 17 years compared to adults following receipt of the 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN. | Day 1 through Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JYNNEOS, Monkeypox, Mpox, MVA-BN, Open-label, Pediatric, Phase 2, Public Health, Random, Vaccine