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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Not yet recruiting

CT.gov ID

NCT05740982

Collaborator

(none)

400

Enrollment

Locations

Arms

20.6

Anticipated Duration (Months)

28.6

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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. 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.

Condition or Disease	Intervention/Treatment	Phase
Monkeypox	Biological: JYNNEOS	Phase 2

Detailed Description

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. 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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 4 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=210	Biological: JYNNEOS 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.
Experimental: 5 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=210	Biological: JYNNEOS 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.

Arm

Intervention/Treatment

Active Comparator: 4

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=210

Biological: JYNNEOS

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.

Experimental: 5

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=210

Biological: JYNNEOS

Outcome Measures

Primary Outcome Measures

Change from baseline Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) [Day 1 through Day 43]
To determine if peak humoral immune responses following an ID regimen of 2 x 10^7 TCID50 MVA-BN and 1 x 10^7 TCID50 MVA BN are non-inferior to the licensed regimen of 1 x 10^8 MVA-BN administered SC in adults ages 18-50 years and 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.
Occurrence of Adverse Events of Special Interest (AESI). [Day 1 through Day 210]
Frequency and description of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years.
Occurrence of Medically Attended Events (MAAE) [Day 1 through Day 210]
Frequency and description of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC
Occurrence of Serious Adverse Events (SAEs) [Day 1 through Day 394]
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.
Occurrence of solicited Adverse Events (AE). [Day 1 through Day 36]
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.
Occurrence of unsolicited Adverse Events (AE) [Day 1 through Day 57]
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.
Occurrence of withdrawals and discontinuations of vaccination. [Day 1 through Day 394]
Frequency of occurrence within adolescents ages 12 to 17 years

Secondary Outcome Measures

Change from baseline in peak Geometric Mean Titers (GMT) [Day 1 through Day 365]
Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) [Day 1 through 365]
For adult arms (1 - 3)
Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) [Day 1 through Day 394]
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
Frequency of withdrawals or discontinuation of vaccination [Day 1 through Day 181]
Frequency in each study arm
Occurrence of Adverse Event of Special Interest [Day 1 through day 210]
Between adolescent and adult study arms.
Occurrence of Adverse Events (AE) [Day 1 through Day 394]
Occurrence and severity of solicited systemic and local AEs to compare relative safety and reactogenicity between adolescent and adult study arms.
Occurrence of Medically Attended Events (MAAE) in adolescent and adult study arms [Day 1 through day 210]
Frequency and description between adolescent and adult study arms.
Occurrence of Medically Attended Events (MAAE) in each study arm [Day 1 through Day 181]
Frequency and relatedness in each study arm
Occurrence of Serious Adverse Events (SAE) in adolescent and adult study arms [Day 1 through 394]
Frequency and relatedness between adolescent and adult study arms
Occurrence of Serious Adverse Events (SAE) in each study arm [Day 1 through Day 181]
Frequency and relatedness in each study arm
Occurrence of solicited Adverse Events (AE) for 14 days after each vaccination in study arms 1-3 [Day 1 through Day 43]
Frequency, severity, and relatedness of solicited systemic and local Adverse Events for 14 days after each vaccination
Occurrence of solicited Adverse Events (AE) for 7 days after each vaccination in study arms 4-5 [Day 1 through Day 29]
Frequency, severity, and relatedness of solicited systemic and local Adverse Events for 7 days after each vaccination between adolescent and adult study arms
Occurrence of unsolicited Adverse Events (AE) [Day 1 through Day 57]
Frequency, severity, and relatedness of unsolicited Adverse Events for 28 days after each vaccination; in each study arm
Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) half-life (t ½) [Day 1 through Day 365]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 in the 4 weeks prior to signing ICF and 4 weeks after each 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Children's of Alabama - Clinical Virology	Birmingham	Alabama	United States	35233-1711
2	The George Washington University Medical Faculty Associates - Infectious Diseases	Washington	District of Columbia	United States	20037
3	National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section	Bethesda	Maryland	United States	20892-1504
4	Brigham and Women's Hospital - Infectious Diseases	Boston	Massachusetts	United States	02115-6110
5	Saint Louis University - Center for Vaccine Development	Saint Louis	Missouri	United States	63104-1015
6	Washington University School of Medicine in St. Louis - Infectious Diseases	Saint Louis	Missouri	United States	63110-1010
7	University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases	Rochester	New York	United States	14642-0001
8	Duke Human Vaccine Institute - Duke Vaccine and Trials Unit	Durham	North Carolina	United States	27703
9	Children's Hospital of Philadelphia - The Center for Pediatric Clinical Effectiveness	Philadelphia	Pennsylvania	United States	19146
10	Children's Hospital of Pittsburgh of UPMC - General Academic Pediatric	Pittsburgh	Pennsylvania	United States	15213
11	Vanderbilt University Medical Center - Infectious Diseases	Nashville	Tennessee	United States	37212
12	Baylor College of Medicine - Molecular Virology and Microbiology	Houston	Texas	United States	77030-3411
13	Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases	Seattle	Washington	United States	98101-1466
14	Ponce School of Medicine CAIMED Center	Ponce		Puerto Rico	00716