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

Sponsor

ModernaTX, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06033261

Collaborator

(none)

300

Enrollment

Locations

Arms

20.9

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Genital Herpes	Biological: mRNA-1608 Biological: BEXSERO	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 6, 2023

Anticipated Primary Completion Date :

Jun 4, 2025

Anticipated Study Completion Date :

Jun 4, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Number of Genital Herpes Recurrences, Counted Starting 14 Days After the Second Study Injection to 6 Months After Second Study Injection [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 [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) [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) [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) [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) [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 [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 [Baseline (Day 1), Days 85 and 225]
Number of Participants With Vaccine Seroresponse [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35205
2	Noble Clinical Research	Tucson	Arizona	United States	85704
3	Cedars-Sinai Medical Center/Carbon Health	Beverly Hills	California	United States	90211
4	Artemis Institute for Clinical Research	Riverside	California	United States	92503
5	Acclaim Clinical Research	San Diego	California	United States	92120
6	Multi-Therapeutic Research Associates, Inc.	Lake City	Florida	United States	32055
7	Suncoast Research Associates, LLC	Miami	Florida	United States	33173
8	University of Illinois Medical Center	Chicago	Illinois	United States	60612
9	Johnson County Clin-Trials (JCCT)	Lenexa	Kansas	United States	66219
10	Heartland Research Associates LLC	Newton	Kansas	United States	67114
11	Fenway Health	Boston	Massachusetts	United States	02215
12	The Center for Pharmaceutical Research	Kansas City	Missouri	United States	64114
13	Velocity Clinical Research	Grand Island	Nebraska	United States	68803
14	Velocity Clinical Research	Norfolk	Nebraska	United States	68701
15	Rochester Clinical Research	Rochester	New York	United States	14609
16	University of North Carolina (UNC) - Kidney Center (UNCKC)	Chapel Hill	North Carolina	United States	27599
17	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612
18	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
19	Velocity Clinical Research, Austin	Cedar Park	Texas	United States	78613
20	Helios CR, Inc Fort Worth	Fort Worth	Texas	United States	76107
21	DM Clinical Research	Houston	Texas	United States	77081
22	Sun Research Institute	San Antonio	Texas	United States	78215
23	Texas Center for Drug Development, INC	Tomball	Texas	United States	77064
24	Health Research of Hampton Roads	Newport News	Virginia	United States	23606
25	University of Washington Virology Research Clinic	Seattle	Washington	United States	98104