A Study of mRNA-1608, a Herpes Simplex Virus -2 (HSV-2) Therapeutic Candidate Vaccine, in Healthy Adults 18 to 55 Years of Age With Recurrent HSV-2 Genital Herpes

• ClinicalTrials.gov Identifier: NCT06033261
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2023
• Last Update Posted: April 3, 2024
• Sponsor: ModernaTX, Inc.
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: September 5, 2023
• First Posted Date: September 13, 2023
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: September 6, 2023
• Estimated Primary Completion Date: June 4, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2023)

• Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) [ Time Frame: Up to Day 64 (7 days after each injection) ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 85 (28 days after each injection) ]
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Day 1 to Day 393 (end of study [EoS]) ]
• Number of Participants with Adverse Events of Special Interest (AESIs) [ Time Frame: Day 1 to Day 393 (EoS) ]
• Number of Participants with AEs Leading to Discontinuation From Study [ Time Frame: Day 1 to Day 393 (EoS) ]
• Number of Participants with Medically-Attended AEs (MAAEs) [ Time Frame: Day 1 through 6 months after last study injection (Day 225) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 5, 2023)

• Number of Genital Herpes Recurrences, Counted Starting 14 Days After the Second Study Injection to 6 Months After Second Study Injection [ Time Frame: Day 71 to Day 225 ]
• Number of Genital Herpes Recurrences, Counted Starting 14 Days After the Second Study Injection to 12 Months After Second Study Injection [ Time Frame: Day 71 to Day 393 ]
• Change From Baseline (28 Days Prior to the First Study Injection) to 2 Months After the Second Study Injection in Genital Herpes Lesion Rate (Proportion of Days With Lesions Present) [ Time Frame: Baseline (Day -27 to Day 1), Day 85 to Day 113 ]
  To calculate the 'Change from Baseline', the herpes lesion rate during the timeframe of Day 85 to Day 113 will be compared against the herpes lesion rate during the timeframe of Day -27 to Day 1 (Baseline).
• Change From Baseline (28 Days Prior to the First Study Injection) to 6 Months After the Second Study Injection in Genital Herpes Lesion Rate (Proportion of Days With Lesions Present) [ Time Frame: Baseline (Day -27 to Day 1), Day 197 to Day 225 ]
  To calculate the 'Change from Baseline', the herpes lesion rate during the timeframe of Day 197 to Day 225 will be compared against the herpes lesion rate during the timeframe of Day -27 to Day 1 (Baseline).
• Change From Baseline (28 Days Prior to the First Study Injection) to 2 Months After the Second Study Injection in HSV-2 Genital Shedding Rate (Proportion of HSV-2 Deoxyribonucleic acid [DNA] Positive Anogenital Swabs) [ Time Frame: Baseline (Day -27 to Day 1), Day 85 to Day 113 ]
  To calculate the 'Change from Baseline', the HSV-2 genital shedding rate during the timeframe of Day 85 to Day 113 will be compared against the HSV-2 genital shedding rate during the timeframe of Day -27 to Day 1 (Baseline).
• Change From Baseline (28 Days Prior to the First Study Injection) to 6 Months After the Second Study Injection in HSV-2 Genital Shedding Rate (Proportion of HSV-2 DNA Positive Anogenital Swabs) [ Time Frame: Baseline (Day -27 to Day 1), Day 197 to Day 225 ]
  To calculate the 'Change from Baseline', the HSV-2 genital shedding rate during the timeframe of Day 197 to Day 225 will be compared against the HSV-2 genital shedding rate during the timeframe of Day -27 to Day 1 (Baseline).
• Geometric Mean Titer (GMT) of mRNA-1608 Antigen-Specific Binding Antibodies (bAbs) at 1 and 6 Months After the Second Study Injection [ Time Frame: Days 85 and 225 ]
• Geometric Mean Fold Rise (GMFR) of mRNA-1608 Antigen-Specific bAbs From Baseline to 1 and 6 Months After the Second Study Injection [ Time Frame: Baseline (Day 1), Days 85 and 225 ]
• Number of Participants With Vaccine Seroresponse [ Time Frame: Baseline (Day 1), Days 85 and 225 ]
  Seroresponse is defined by an increase in HSV-2 bAb levels at Day 85 and Day 225 ≥4-fold if baseline level is above the lower level of quantitation (LLOQ) or ≥4 × LLOQ if baseline bAb level is <LLOQ prior to study injection.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of mRNA-1608, a Herpes Simplex Virus -2 (HSV-2) Therapeutic Candidate Vaccine, in Healthy Adults 18 to 55 Years of Age With Recurrent HSV-2 Genital Herpes
• Official Title: A Phase 1/2, Randomized, Observer-Blind, Controlled, Dose-Ranging Study of mRNA-1608, an HSV-2 Therapeutic Candidate Vaccine, in Healthy Adults 18 to 55 Years of Age With Recurrent HSV-2 Genital Herpes
• Brief Summary: The purpose of this study is to generate safety and immunogenicity data and establish a proof-of-concept of clinical benefit of the mRNA-1608 vaccine candidate.
• Detailed Description: Participants with a history of recurrent genital herpes will be randomly assigned in a 1:1:1:1 ratio to receive mRNA-1608 at 1 of the 3 dose levels or control (BEXSERO) administered as 2 doses at 0 and 2 months (Day 1 and Day 57).
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Genital Herpes

Intervention

• Biological: mRNA-1608
  Sterile liquid for injection
• Biological: BEXSERO
  A vaccine indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B.

Study Arms

• Experimental: mRNA-1608 Dose A
  Participants will receive 2 intramuscular (IM) injections of mRNA-1608 at Dose Level A, each dose administered at 0 and 2 months (Day 1 and Day 57).
  Intervention: Biological: mRNA-1608
• Experimental: mRNA-1608 Dose B
  Participants will receive 2 IM injections of mRNA-1608 at Dose Level B, each dose administered at 0 and 2 months (Day 1 and Day 57).
  Intervention: Biological: mRNA-1608
• Experimental: mRNA-1608 Dose C
  Participants will receive 2 IM injections of mRNA-1608 at Dose Level C, each dose administered at 0 and 2 months (Day 1 and Day 57).
  Intervention: Biological: mRNA-1608
• BEXSERO
  Participants will receive 2 IM injections of BEXSERO, each dose administered at 0 and 2 months (Day 1 and Day 57).
  Intervention: Biological: BEXSERO

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 14, 2024): 365
• Original Estimated Enrollment (submitted: September 5, 2023): 300
• Estimated Study Completion Date: June 4, 2025
• Estimated Primary Completion Date: June 4, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has a diagnosis of genital HSV-2 infection for at least 1 year before the Screening Visit.
• Seropositive for HSV-2 as determined by Western Blot.
• Participant has a history of recurrent genital herpes defined as at least 3 and no more than 9 reported genital herpes recurrences in the 12 months preceding the Screening Visit, or if currently on suppressive therapy, prior to initiation of suppressive therapy.
• Willing to refrain from taking suppressive antiviral therapy from the Screening Visit until the end of the study.
• Willing to refrain from the use of episodic antiviral therapy during the three 28-day anogenital swabbing periods. Episodic therapy may be used outside the three 28-day swabbing periods.
• For female participants of childbearing potential: negative pregnancy test, adequate contraception, and not currently breastfeeding.

Exclusion Criteria:

• Prior immunization with a vaccine containing HSV antigens.
• History of any form of ocular HSV infection, HSV-related erythema multiforme, or HSV-related neurological complications.
• History of genital HSV-1 infection.
• History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) types 1 or 2 (HIV-1, HIV-2).
• Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA vaccine(s) or any components of the mRNA vaccines.
• Previously received BEXSERO or other vaccine to prevent serogroup B meningococcal disease (also known as meningitis B).
• History of allergic disease or reactions likely to be exacerbated by any component of BEXSERO vaccine.
• Has received or plans to receive any licensed or authorized vaccine, including COVID-19 vaccines, ≤ 28 days prior to the first study injection (Day 1), or plans to receive a licensed or authorized vaccine within 28 days before or after study injection with the exception of licensed influenza vaccines, which may be received more than 14 days before or after any study injection.

Note: Other inclusion and exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06033261
• Other Study ID Numbers: mRNA-1608-P101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ModernaTX, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ModernaTX, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ModernaTX, Inc.
• Verification Date: April 2024