Clinical trial NCT05512949: Trial to Evaluate the Immunogenicity of Dose Reduction Strategies of the MVA-BN Monkeypox Vaccine
Official title: A Phase 2 Randomized, Open-Label, Multisite Trial to Evaluate the Immunogenicity of Dose Reduction Strategies of the MVA-BN Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Monkeypox
Keywords: Dose Reduction
Immunogenicity
JYNNEOS
Monkeypox
MVA-BN
Open-Label
Randomized
Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2022-08-23
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two intradermal (ID) regimens for Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine compared to the standard subcutaneous (SC) regimen in healthy, vaccinia-naïve adults 18 to 50 years of age, inclusive. At least 210 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.

The study will enroll a 1:1:1 randomization allocation. Participants will not be stratified by clinical trial site, demographic characteristics or human immunodeficiency virus (HIV) infection status; however, these data will be collected during screening and enrollment. Each participant may be screened either in a separate visit in the 7 days prior to Day 1 or on Day 1.

The primary hypothesis involves a two-step hierarchical process. The study will first test non-inferiority of the 2 x 10\^7 ID regimen relative to 1 x 10\^8 SC (standard dose regimen). If the 2 x 10\^7 ID regimen is non-inferior to the standard dose regimen, hypothesis testing will proceed to test non-inferiority of the 1 x 10\^7 ID regimen relative to the standard dose regimen.

The primary objectives are: 1) to determine if peak humoral immune responses following an ID regimen of 2 x 10\^7 50% Tissue Culture Infectious Dose (TCID50) MVA-BN are non-inferior to the licensed regimen of 1 x 10\^8 MVA-BN administered SC; 2) to determine if peak humoral immune responses following an ID regimen of 1 x 10\^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10\^8 MVA-BN administered SC.

Detailed description: This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two intradermal (ID) regimens for Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine compared to the standard subcutaneous (SC) regimen. This study will enroll healthy, non-pregnant, non-breastfeeding adults 18 to 50 years old inclusive. Participants with stable medical conditions and well-controlled human immunodeficiency virus (HIV) infection can participate. At least 210 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.

The study will enroll a 1:1:1 randomization allocation. Participants will not be stratified by clinical trial site, demographic characteristics or HIV infection status; however, these data will be collected during screening and enrollment. Each participant may be screened either in a separate visit in the 7 days prior to Day 1 or on Day 1.

The primary hypothesis involves a two-step hierarchical process. The study will first test non-inferiority of the 2 x 10\^7 ID regimen relative to 1 x 10\^8 SC (standard dose regimen). If the 2 x 10\^7 ID regimen is non-inferior to the standard dose regimen, hypothesis testing will proceed to test non-inferiority of the 1 x 10\^7 ID regimen relative to the standard dose regimen.

The primary objectives are: 1) to determine if peak humoral immune responses following an ID regimen of 2 x 10\^7 50% Tissue Culture Infectious Dose (TCID50) MVA-BN are non-inferior to the licensed regimen of 1 x 10\^8 MVA-BN administered SC; 2) to determine if peak humoral immune responses following an ID regimen of 1 x 10\^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10\^8 MVA-BN administered SC.

The secondary objectives are: 1) to determine if individual peak humoral immune responses following each ID regimen are non-inferior to the licensed regimen administered SC; 2) to evaluate humoral immune responses of each ID regimen (separately) compared to licensed SC regimen each study day; 3) to evaluate the kinetics of the humoral immune responses of each ID regimen (separately) compared to licensed SC regimen through Day 365; 4) To compare relative safety among study arms as assessed by systemic and local reactogenicity for 14 days after each vaccination, unsolicited adverse events for 28 days after each vaccination, and serious adverse events (SAE) and medically attended events (MAAE) from Day 1 through Day 57, and related SAE/MAAEs through Day 181.

Eligibility criteria: Inclusion Criteria:

1. Individuals 18 - 50 years of age inclusive at the time of consent.
2. 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.
3. Agreement to adhere to Lifestyle Considerations during the study.
4. 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.
5. In good general health as evidenced by medical history, physical examination, and clinical judgement of the investigator to be in stable state of health.

   \*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.
6. If HIV infected individual, they must be on suppressive Antiretroviral therapy (ART) for at least 6 months, report a cluster of differentiation 4 (CD4) count of greater than 350 cells/uL and no Acquired Immune Deficiency Syndrome (AIDS)-defining illness in the last year.

Exclusion Criteria:

1. Ever received a licensed or an investigational smallpox or monkeypox vaccine.

   \*This includes Dryvax, Acam2000, LC 16 m8, Modified Vaccinia Ankara (MVA)-based vaccine candidate or licensed vaccines, and Jynneos, Imvamune or Imvanex).
2. Any history of monkeypox, cowpox, or vaccinia infection.
3. Close contact of anyone known to have monkeypox in the 3 weeks prior to signing Informed Consent Form (ICF).
4. Immunocompromised as determined by the investigator.
5. 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.
6. Pregnant or breast feeding.
7. Received or plans to receive a live vaccine in the 4 weeks prior to signing ICF and 4 weeks after each vaccination.
8. Received or plans to receive any other vaccine in the 2 weeks prior to signing ICF through Day 43.
9. Received experimental therapeutic agent or vaccine in the 3 months prior to signing ICF.
10. 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.
11. Has tattoos, scars, or other marks which would, in the opinion of the investigator, interfere with assessment of the vaccination site.
12. Has any medical disease or condition that, in the opinion of the participating site Principal Investigator (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.

Primary outcomes:
measure: Vaccinia Virus Specific Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at Day 43
timeFrame: Day 43
Secondary outcomes:
measure: Individual Peak GMT Through Day 365
timeFrame: Day 1 through Day 365
measure: Vaccinia Virus Specific PRNT GMT at Study Day 1, 15, 29, 43, 57, 90, 181, and 365
timeFrame: Day 1 through Day 365
measure: Vaccinia Virus Specific PRNT Half-life (t ½)
timeFrame: Day 43 through Day 365
measure: Number of Participants Reporting Solicited Systemic AEs Through 14 Days After Each Study Vaccination
timeFrame: Day 1 through Day 43
measure: Number of Participants Reporting Solicited Local AEs Through 14 Days After Each Study Vaccination
timeFrame: Day 1 through Day 43
measure: Number of Participants Reporting Unsolicited Related and Unrelated Adverse Events (AEs) Through 28 Days After Each Vaccination
timeFrame: Day 1 through Day 57
measure: Number of Participants Reporting Related and Unrelated Medically Attended Adverse Events (MAAEs)
timeFrame: Day 1 through Day 181
measure: Number of Participants Reporting Related and Unrelated Serious Adverse Events (SAEs)
timeFrame: Day 1 through Day 181
measure: Number of Participants Who Withdrew or Discontinued Vaccination
timeFrame: Day 1 through Day 365
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego (UCSD) - Antiviral Research Center (AVRC)
state: California
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Decatur
country: United States
facility: The Hope Clinic of Emory University
state: Georgia
city: Bethesda
country: United States
facility: NIH Clinical Research Center, Investigational Drug Management and Research Section
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis University Center for Vaccine Development
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: