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

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

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.

Study Overview

• Status: Completed
• Conditions: Genital Herpes
• Intervention / Treatment: Biological: mRNA-1608; Biological: BEXSERO

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
• Enrollment (Actual): 303
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35218
      • Accel Clinical Sites Network - Cahaba Medical Care
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center/Carbon Health
    • San Diego, California, United States, 92120
      • Acclaim Clinical Research
  • Florida
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates, LLC
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials (JCCT)
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70125
      • Research Works
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Fenway Health
  • Michigan
    • Southfield, Michigan, United States, 48076
      • DM Clinical Research
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Velocity Clinical Research
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Velocity Clinical Research Cleveland
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Velocity Clinical Research, Austin
    • Fort Worth, Texas, United States, 76107
      • Helios CR, Inc Fort Worth
    • Houston, Texas, United States, 77081
      • DM Clinical Research
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • Tomball, Texas, United States, 77064
      • DM Clinical Research
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Virology Research Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Biological: mRNA-1608; Sterile liquid for injection
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).	Biological: mRNA-1608; Sterile liquid for injection
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).	Biological: mRNA-1608; Sterile liquid for injection
Other: BEXSERO; Participants will receive 2 IM injections of BEXSERO, each dose administered at 0 and 2 months (Day 1 and Day 57).	Biological: BEXSERO; A vaccine indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local and Systemic ARs	Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Up to Day 64 (Within 7 days after study vaccination)
Number of Participants With Unsolicited Adverse Events (AEs)	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time [PT]/partial thromboplastin time [PTT]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Up to Day 85 (Up to 28 days after study vaccination)
Number of Participants With Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs Leading to Study Discontinuation	An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly/birth defect, or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor were required. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Day 1 through Day 393
Number of Participants With Medically Attended AEs (MAAEs)	A MAAE is an AE that led to an unscheduled visit to a healthcare practitioner. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Day 1 through Day 393

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Genital Herpes Recurrence Episode Per Participant, Counted Starting 14 Days After the Second Study Injection to 6 Months After Second Study Injection	An episode of recurrence was defined as one or more consecutive "yes" to the "Do you have genital herpes lesion?" question either from Genital Herpes Signs and Symptoms (GHSS) or daily recurrence eDiary within a 14-day period from the first "yes" response regardless of "no" or missing entries in between. The start date of an episode was the first date of "yes" response, and the end date of an episode was the last date of "yes" within the episode. The recurrence analysis period up to 6 months included the time from 14 days after the second injection until the last GHSS or daily recurrence eDiary collected up to the 1) the Day 225 visit date or 2) if Day 225 visit date is not available, the earliest of study Day 225 or study discontinuation date.	Day 71 up to Day 225
Number of Genital Herpes Recurrence Episode Per Participant, Counted Starting 14 Days After the Second Study Injection to 12 Months After Second Study Injection	An episode of recurrence was defined as one or more consecutive "yes" to the "Do you have genital herpes lesion?" question either from GHSS or daily recurrence eDiary within a 14-day period from the first "yes" response regardless of "no" or missing entries in between. The start date of an episode was the first date of "yes" response, and the end date of an episode was the last date of "yes" within the episode. The recurrence analysis period up to 12 months included the time from 14 days after the second injection until the last GHSS or daily recurrence eDiary collected up to the 1) the Day 393 visit date or 2) if Day 393 visit date is not available, the earliest of study Day 393 or study discontinuation date.	Day 71 up 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 (Percentage of Days With Lesions Present)	Genital herpes lesion rate was defined for each 28-day swabbing period as the number of days with lesion present according to the eDiary divided by the number of days during the 28-day swabbing period.	Baseline (Day -27 to Day 1), Day 113
Change From Baseline (28 Days Prior to the First Study Injection) to 6 Months After the Second Study Injection in Genital Herpes Lesion Rate (Percentage of Days With Lesions Present)	Genital herpes lesion rate was defined for each 28-day swabbing period as the number of days with lesion present according to the eDiary divided by the number of days during the 28-day swabbing period.	Baseline (Day -27 to Day 1), Day 225
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 (Percentage of HSV-2 Deoxyribonucleic Acid [DNA] Positive Anogenital Swabs)	Genital shedding rate was defined for each 28-day swabbing period as the number of anogenital swabs with HSV-2 DNA positive results (that is, positive results per polymerase chain reaction [PCR]) divided by the number of swabs during the swabbing period.	Baseline (Day -27 to Day 1), Day 113
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 (Percentage of HSV-2 DNA Positive Anogenital Swabs)	Genital shedding rate was defined for each 28-day swabbing period as the number of anogenital swabs with HSV-2 DNA positive results (that is, positive results per PCR) divided by the number of swabs during the swabbing period.	Baseline (Day -27 to Day 1), Day 225
Geometric Mean (GM) Value of mRNA-1608 Antigen-Specific Binding Antibodies (bAbs)	Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5 * LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ if actual values were not available. LLOQ was 1220 units (U)/milliliter (mL) and ULOQ was 6890000 U/mL for HSV2 gB. LLOQ was 1230 U/mL and ULOQ was 21300000 U/mL for HSV2 gC. LLOQ was 2220 U/mL and ULOQ was 23900000 U/mL for HSV2 gD. 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values for GM, then back transformed to the original scale for presentation.	Days 85 and 197
Geometric Mean Fold Rise (GMFR) of mRNA-1608 Antigen-Specific bAbs	Antibody values reported as below the LLOQ were replaced by 0.5 * LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 1220 U/mL and ULOQ was 6890000 U/mL for HSV2 gB. LLOQ was 1230 U/mL and ULOQ was 21300000 U/mL for HSV2 gC. LLOQ was 2220 U/mL and ULOQ was 23900000 U/mL for HSV2 gD. 95% CI was calculated based on the t-distribution of the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation.	Days 85 and 197
Percentage of Participants With Vaccine Seroresponse	Seroresponse was defined as a change from baseline below the LLOQ to equal or above 4 * LLOQ, or at least a 4-fold rise if baseline was equal to or above the LLOQ. LLOQ was 1220 U/mL and ULOQ was 6890000 U/mL for HSV2 gB. LLOQ was 1230 U/mL and ULOQ was 21300000 U/mL for HSV2 gC. LLOQ was 2220 U/mL and ULOQ was 23900000 U/mL for HSV2 gD. 95% CI was calculated using the Clopper-Pearson method.	Day 85

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Actual): April 25, 2025
• Study Completion (Actual): April 25, 2025

Study Registration Dates

• First Submitted: September 5, 2023
• First Submitted That Met QC Criteria: September 5, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: HSV-2; Genital Herpes; Herpes Simplex Virus Type 2; HSV-2 vaccine; mRNA-1608
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Virus Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Herpesviridae Infections; Herpes Simplex; Herpes Genitalis; 4CMenB vaccine
• Other Study ID Numbers: mRNA-1608-P101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No