Genital Herpes
Conditions
Keywords
HSV-2, Herpes Simplex Virus Type 2, HSV-2 vaccine, Genital Herpes, mRNA-1608
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).
Interventions
BIOLOGICALmRNA-1608
Sterile liquid for injection
BIOLOGICALBEXSERO
A vaccine indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B.
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs Leading to Study Discontinuation | Day 1 through Day 393 | 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. |
| Number of Participants With Medically Attended AEs (MAAEs) | Day 1 through Day 393 | 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. |
| Number of Participants With Solicited Local and Systemic ARs | Up to Day 64 (Within 7 days after study vaccination) | 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. |
| Number of Participants With Unsolicited Adverse Events (AEs) | Up to Day 85 (Up to 28 days after study vaccination) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean (GM) Value of mRNA-1608 Antigen-Specific Binding Antibodies (bAbs) | Days 85 and 197 | 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. |
| Geometric Mean Fold Rise (GMFR) of mRNA-1608 Antigen-Specific bAbs | Days 85 and 197 | 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. |
| Percentage of Participants With Vaccine Seroresponse | Day 85 | 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. |
| Number of Genital Herpes Recurrence Episode Per Participant, Counted Starting 14 Days After the Second Study Injection to 6 Months After Second Study Injection | Day 71 up to Day 225 | 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. |
| 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) | Baseline (Day -27 to Day 1), Day 113 | 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. |
| Number of Genital Herpes Recurrence Episode Per Participant, Counted Starting 14 Days After the Second Study Injection to 12 Months After Second Study Injection | Day 71 up to Day 393 | 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. |
| 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) | Baseline (Day -27 to Day 1), Day 225 | 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. |
| 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) | Baseline (Day -27 to Day 1), Day 113 | 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. |
| 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) | Baseline (Day -27 to Day 1), Day 225 | 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. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 38.8 years STANDARD_DEVIATION 8.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 79 Participants |
| Race/Ethnicity, Customized Race Multiple | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Race Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants |
| Race/Ethnicity, Customized Race White | 48 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 75 | 0 / 76 | 0 / 76 |
| other Total, other adverse events | 4 / 76 | 1 / 75 | 0 / 76 | 1 / 75 |
| serious Total, serious adverse events | 0 / 76 | 2 / 75 | 2 / 76 | 2 / 75 |
Outcome results
None listed