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Safety and Efficacy of 4 Investigational HSV 2 Vaccines in Adults With Recurrent Genital Herpes Caused by HSV 2

Phase 1
Terminated
Conditions
Genital Herpes
Interventions
Biological: HSV 2 Formulation 3
Biological: HSV 2 Formulation 1
Biological: HSV 2 Formulation 2
Biological: HSV 2 Formulation 6
Biological: HSV 2 Formulation 4
Biological: HSV 2 Formulation 5
Biological: Sodium Chloride 0.9%
Registration Number
NCT04222985
Lead Sponsor
Sanofi Pasteur, a Sanofi Company
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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
24
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part A - Group 4HSV 2 Formulation 3HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part A - Group 4HSV 2 Formulation 4HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part A - Group 4Sodium Chloride 0.9%HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part A - Group 5HSV 2 Formulation 3HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2.
Part B (Stage 2) - Group 1HSV 2 Formulation 1HSV 2 Formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 2Sodium Chloride 0.9%HSV 2 formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 6Sodium Chloride 0.9%Sodium chloride 0.9% (in both arms) at Month 0 and Month 2
Part B (Stage 2) - Group 4HSV 2 Formulation 3HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part B (Stage 2) - Group 4HSV 2 Formulation 4HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part A - Group 2HSV 2 Formulation 2HSV 2 formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 5HSV 2 Formulation 5HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2.
Part B (Stage 1) - Group 1Sodium Chloride 0.9%HSV 2 Formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 1HSV 2 Formulation 1HSV 2 formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 1Sodium Chloride 0.9%HSV 2 formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 3HSV 2 Formulation 3HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 4HSV 2 Formulation 3HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part B (Stage 1) - Group 4HSV 2 Formulation 4HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part B (Stage 1) - Group 5HSV 2 Formulation 5HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2
Part B (Stage 1) - Group 7Sodium Chloride 0.9%HSV 2 Formulation 6 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 3HSV 2 Formulation 3HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part A - Group 3Sodium Chloride 0.9%HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 2HSV 2 Formulation 2HSV 2 Formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 2Sodium Chloride 0.9%HSV 2 Formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 3Sodium Chloride 0.9%HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 6Sodium Chloride 0.9%Sodium Chloride 0.9% (in both arms) at Month 0 and Month 2
Part B (Stage 1) - Group 1HSV 2 Formulation 1HSV 2 Formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 4Sodium Chloride 0.9%HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part B (Stage 1) - Group 6Sodium Chloride 0.9%Sodium Chloride 0.9% (in both arms) at Month 0 and Month 2
Part B (Stage 1) - Group 7HSV 2 Formulation 6HSV 2 Formulation 6 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 3HSV 2 Formulation 3HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 4Sodium Chloride 0.9%HSV 2 Formulation 4 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0, then HSV 2 Formulation 3 administered with concomitantly with 0.9% sodium chloride in the opposite arm at Month 2
Part B (Stage 2) - Group 7Sodium Chloride 0.9%HSV 2 Formulation 6 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 2Sodium Chloride 0.9%HSV 2 Formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 1Sodium Chloride 0.9%HSV 2 Formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 7HSV 2 Formulation 6HSV 2 Formulation 6 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 3Sodium Chloride 0.9%HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 1) - Group 5HSV 2 Formulation 3HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2
Part B (Stage 2) - Group 2HSV 2 Formulation 2HSV 2 Formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2
Part B (Stage 2) - Group 5HSV 2 Formulation 3HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2
Part B (Stage 2) - Group 5HSV 2 Formulation 5HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2
Primary Outcome Measures
NameTimeMethod
Number of participants with unsolicited adverse eventsWithin 30 days after vaccination

An unsolicited adverse event is an event that does not fulfill the conditions prelisted in the Case Report Book in terms of diagnosis and/or onset post-vaccination

Number of participants with adverse events of special interest (AESIs)From Day 0 to Month 14

AESIs are collected throughout the study

Number of participants with medically-attended adverse events (MAAEs)From Day 0 to Month 14

An MAAE is a new onset or a worsening of a condition that prompts the participant to seek unplanned medical advice at a physician's office or Emergency Department

Number of participants with serious adverse events (SAEs)From Screening to Month 14

SAEs are collected throughout the study

Genital HSV recurrence6 months following the second vaccination

Proportion of participants free of genital HSV recurrence following the second vaccination

Number of participants with immediate adverse eventsWithin 4 hours (participants in Part A) or 30 minutes (participants in Part B) after vaccination

Unsolicited systemic adverse events occurring immediately after vaccination

Number of participants with solicited injection site and systemic reactionsWithin 7 days after vaccination

Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills

Number of participants with out-of-range biological test resultsFrom Day 8 to Day 30

Out-of-range biological test results area assessed at Days 8 and 30 after each vaccination and 15 days prior to second vaccination in Part A and Days 8 and 30 after each vaccination in Part B

Viral genital shedding rate60 days before first vaccination and 60 days after the second vaccination

Relative change in HSV DNA detection frequency between swabs collected before the first vaccination and those collected after the second vaccination visit

Secondary Outcome Measures
NameTimeMethod
Genital HSV recurrence60 days following the second vaccination

Number of recurrences of genital HSV following the second vaccination in participants who receive investigational product or placebo. Recurrence is defined as the appearance of genital and perineal lesions (i.e., shingles, blisters, ulcers) in a previously asymptomatic participant. Regarding 2 separate episodes of recurrences, recurrence is defined as the presentation of a new lesion (or lesions) after a 1-day-minimum (≥ 24 hours) lesion-free period

Change in serum HSV 2-antibody levelsBefore and 30 days after the first and second vaccinations and 6 months after the second vaccination

Change between pre-vaccination and post-first and second vaccinations

Viral genital shedding rate after the first and second vaccination60 days before first vaccination, and 60 days after the first vaccination, plus 60 days after the second vaccination

Relative change in HSV DNA detection frequency between swabs collected before the first vaccination visit and those collected 60 days after the first vaccination visit plus after the second vaccination visit in participants who receive investigational product or placebo

Change in level of HSV 2-specific cellular immune responsesBefore and 8 days after the first and second vaccination and 6 months after the second vaccination

Change between pre-vaccination and post-first and second vaccinations

Genital lesion rate6 months after the second vaccination

Total number of days that the participants who receive investigational product or placebo report genital herpes lesions following the second vaccination

Viral genital shedding rate after the first vaccination60 days before and 60 days after the first vaccination

Relative change in HSV DNA detection frequency between swabs collected before the first vaccination visit and those collected 60 days after the first vaccination visit in participants who receive investigational product or placebo

Trial Locations

Locations (4)

M3 Wake Research Inc-Site Number:8400006

🇺🇸

Raleigh, North Carolina, United States

Brigham and Womens Hospital-Site Number:8400003

🇺🇸

Boston, Massachusetts, United States

Research Centers of America-Site Number:8400010

🇺🇸

Hollywood, Florida, United States

University of Washington Virology Research Clinic-Site Number:8400001

🇺🇸

Seattle, Washington, United States

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