Clinical trial NCT04222985: Safety and Efficacy of 4 Investigational HSV 2 Vaccines in Adults With Recurrent Genital Herpes Caused by HSV 2
Official title: Safety and Efficacy of 4 Investigational HSV 2 Vaccines Administered by Intramuscular Route in Adults With Recurrent Genital Herpes Caused by HSV 2
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Genital Herpes
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
First posted: 2020-01-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are:

* To describe the safety profile of different investigational vaccine regimens against herpes simplex virus type 2 (HSV-2).
* To evaluate the efficacy of the investigational vaccine regimens with respect to:
* the frequency of herpes simplex virus (HSV) deoxyribonucleic acid (DNA) detection in the genital area (shedding rate) following a 2 dose vaccine schedule
* the proportion of participants free of HSV genital recurrence at 6 months after the 2-dose vaccine schedule

The secondary objectives of the study are:

* To describe the impact of each of the investigational vaccine regimens in terms of total number of days with genital lesion up to 6 months after vaccination 2 and number of recurrences 60 days after the second vaccination compared with the placebo group
* To describe the efficacy of each of the investigational vaccine regimens with respect to the frequency of HSV DNA detection in the genital area (shedding rate) 60 days following the first vaccination visit plus 60 days following the second vaccination visit compared with the placebo group
* To describe the efficacy of each of the investigational vaccine regimens with respect to the frequency of HSV DNA detection in the genital area (shedding rate) 60 days following the first vaccination visit compared with the placebo group

Detailed description: Study duration per participant is approximately 16 months

Eligibility criteria: Inclusion criteria :

* Aged 18 to 55 years on the day of inclusion
* Informed consent form has been signed and dated
* Able to attend all scheduled visits and to comply with all trial procedures
* In good general health with absence of significant health problems as determined by medical history, physical examination, and laboratory screening performed during screening visits
* HSV-2 seropositive confirmed by Western blot
* A history of established HSV-2 infection ≥ 1 year
* A history of at least 2 and no more than 9 reported HSV clinical recurrences in the prior 12 months, or, if currently on suppressive therapy, history of at least 2 and no more than 9 reported clinical recurrences in the 12 months prior to initiation suppressive therapy
* For Part A and Part B, the participant is willing to refrain from using suppressive antiviral therapy starting 5 days before the first vaccination visit and up to 6 months after the second vaccination visit; and for Part B, throughout the 3, 60-day swabbing periods, and up to 6 months after the second vaccination visit
* For Part A and Part B, the participant is willing to refrain from using antiviral therapy to treat recurrences starting 5 days before V01 and up to 6 months after the second vaccination visit; and for Part B, throughout the 3, 60-day swabbing periods (i.e., up to 60 days after the second vaccination visit)

Exclusion criteria:

* For Part A, the participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 6 months after the last vaccination. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile.
* For Part B, the participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence with her/his partner from at least 4 weeks before the enrollment visit until at least 6 months after the last vaccination. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile.
* Participants whose female partners are pregnant at the time of enrollment or plan to become pregnant between study entry through 12 weeks (for Part A) and 6 months (for Part B) after the second vaccination visit.
* Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
* Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
* Receipt of any vaccine in the 4 weeks preceding the first study vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any trial vaccination except for influenza vaccination, which may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccination
* Current alcohol abuse or drug addiction
* Positive serologic test or polymerase chain reaction for human immunodeficiency virus type 1 infection
* Positive hepatitis B surface antigen
* Positive antibody for hepatitis C virusribonucleic acid and positive hepatitis C test
* Severe active infection or serious HSV-2 related medical conditions on the day of enrollment that, in the opinion of the Investigator, would prevent study completion
* Active genital herpes determined by the presence of outbreaks (genital lesions) at the time of enrollment. A prospective subject should not be included in the trial until 24 hours after the outbreak has resolved (the lesions have completely disappeared)
* Hemoglobin, white blood cell count with differential, platelet count, renal function tests (serum creatinine, blood urea nitrogen), liver function tests, creatine phosphokinase and C-reactive protein screening laboratory results that fall into the range of values that are Grade 2 or greater as per the study toxicity grading scale for this study. Also the range of values that are Grade 1 and are deemed clinically significant in the opinion of the Investigator (Grade 1 values deemed not clinically significant may be enrolled at the Investigator's discretion)
* Previous vaccination against HSV infection with either the trial vaccine or another vaccine against HSV
* History of HSV infection of the eye (e.g., herpes simplex interstitial keratitis or uveitis)
* History of eczema herpeticum
* History of herpes-associated erythema multiforme
* History of lesions caused by HSV on either arm
* History of any autoimmune disorder
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
* Receipt of immune globulins, blood or blood-derived products in the past 3 months
* Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgment
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
* Known allergy or intolerance to nickel
* Known allergy or intolerance to acyclovir or valacyclovir
* Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
* Chronic illness or other conditions that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
* Moderate or severe acute illness/infection (according to the Investigator's judgment) on the day of vaccination or febrile illness (temperature ≥ 100.4 °F (\[≥ 38 °C\]).

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of participants with immediate adverse events
timeFrame: Within 4 hours (participants in Part A) or 30 minutes (participants in Part B) after vaccination
measure: Number of participants with solicited injection site and systemic reactions
timeFrame: Within 7 days after vaccination
measure: Number of participants with unsolicited adverse events
timeFrame: Within 30 days after vaccination
measure: Number of participants with medically-attended adverse events (MAAEs)
timeFrame: From Day 0 to Month 14
measure: Number of participants with adverse events of special interest (AESIs)
timeFrame: From Day 0 to Month 14
measure: Number of participants with serious adverse events (SAEs)
timeFrame: From Screening to Month 14
measure: Number of participants with out-of-range biological test results
timeFrame: From Day 8 to Day 30
measure: Viral genital shedding rate
timeFrame: 60 days before first vaccination and 60 days after the second vaccination
measure: Genital HSV recurrence
timeFrame: 6 months following the second vaccination
Secondary outcomes:
measure: Genital lesion rate
timeFrame: 6 months after the second vaccination
measure: Genital HSV recurrence
timeFrame: 60 days following the second vaccination
measure: Viral genital shedding rate after the first and second vaccination
timeFrame: 60 days before first vaccination, and 60 days after the first vaccination, plus 60 days after the second vaccination
measure: Viral genital shedding rate after the first vaccination
timeFrame: 60 days before and 60 days after the first vaccination
measure: Change in serum HSV 2-antibody levels
timeFrame: Before and 30 days after the first and second vaccinations and 6 months after the second vaccination
measure: Change in level of HSV 2-specific cellular immune responses
timeFrame: Before and 8 days after the first and second vaccination and 6 months after the second vaccination
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Research Centers of America-Site Number:8400010
state: Florida
city: Boston
country: United States
facility: Brigham and Womens Hospital-Site Number:8400003
state: Massachusetts
city: Raleigh
country: United States
facility: M3 Wake Research Inc-Site Number:8400006
state: North Carolina
city: Seattle
country: United States
facility: University of Washington Virology Research Clinic-Site Number:8400001
state: Washington
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: