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

NCT04222985 | Terminated Phase 1 FDA Drug

• 2 other identifiers: HSV15U1111-1183-6522
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

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

Conditions

Genital Herpes

Outcome Measures

Primary Outcomes (9)

• Number of participants with immediate adverse events

  Unsolicited systemic adverse events occurring immediately after vaccination

  Within 4 hours (participants in Part A) or 30 minutes (participants in Part B) after vaccination

• Number of participants with solicited injection site and systemic reactions

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

  Within 7 days after vaccination

• Number of participants with unsolicited adverse events

  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

  Within 30 days after vaccination

• Number of participants with medically-attended adverse events (MAAEs)

  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

  From Day 0 to Month 14

• Number of participants with adverse events of special interest (AESIs)

  AESIs are collected throughout the study

  From Day 0 to Month 14

• Number of participants with serious adverse events (SAEs)

  SAEs are collected throughout the study

  From Screening to Month 14

• Number of participants with out-of-range biological test results

  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

  From Day 8 to Day 30

• Viral genital shedding rate

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

  60 days before first vaccination and 60 days after the second vaccination

• Genital HSV recurrence

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

  6 months following the second vaccination

Secondary Outcomes (6)

• Genital lesion rate

  6 months after the second vaccination

• Genital HSV recurrence

  60 days following the second vaccination

• Viral genital shedding rate after the first and second vaccination

  60 days before first vaccination, and 60 days after the first vaccination, plus 60 days after the second vaccination

• Viral genital shedding rate after the first vaccination

  60 days before and 60 days after the first vaccination

• Change in serum HSV 2-antibody levels

  Before and 30 days after the first and second vaccinations and 6 months after the second vaccination

Study Arms (20)

Part A - Group 1

EXPERIMENTAL

HSV 2 formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 1; Biological: Sodium Chloride 0.9%

Part A - Group 2

EXPERIMENTAL

HSV 2 formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 2; Biological: Sodium Chloride 0.9%

Part A - Group 3

EXPERIMENTAL

HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 3; Biological: Sodium Chloride 0.9%

Part A - Group 4

EXPERIMENTAL

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

Biological: HSV 2 Formulation 3; Biological: HSV 2 Formulation 4; Biological: Sodium Chloride 0.9%

Part A - Group 5

EXPERIMENTAL

HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2.

Biological: HSV 2 Formulation 3; Biological: HSV 2 Formulation 5

Part A - Group 6

PLACEBO COMPARATOR

Sodium chloride 0.9% (in both arms) at Month 0 and Month 2

Biological: Sodium Chloride 0.9%

Part B (Stage 1) - Group 1

EXPERIMENTAL

HSV 2 Formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 1; Biological: Sodium Chloride 0.9%

Part B (Stage 1) - Group 2

EXPERIMENTAL

HSV 2 Formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 2; Biological: Sodium Chloride 0.9%

Part B (Stage 1) - Group 3

EXPERIMENTAL

HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 3; Biological: Sodium Chloride 0.9%

Part B (Stage 1) - Group 4

EXPERIMENTAL

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

Biological: HSV 2 Formulation 3; Biological: HSV 2 Formulation 4; Biological: Sodium Chloride 0.9%

Part B (Stage 1) - Group 5

EXPERIMENTAL

HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2

Biological: HSV 2 Formulation 3; Biological: HSV 2 Formulation 5

Part B (Stage 1) - Group 6

PLACEBO COMPARATOR

Sodium Chloride 0.9% (in both arms) at Month 0 and Month 2

Biological: Sodium Chloride 0.9%

Part B (Stage 1) - Group 7

EXPERIMENTAL

HSV 2 Formulation 6 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 6; Biological: Sodium Chloride 0.9%

Part B (Stage 2) - Group 1

EXPERIMENTAL

HSV 2 Formulation 1 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 1; Biological: Sodium Chloride 0.9%

Part B (Stage 2) - Group 2

EXPERIMENTAL

HSV 2 Formulation 2 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 2; Biological: Sodium Chloride 0.9%

Part B (Stage 2) - Group 3

EXPERIMENTAL

HSV 2 Formulation 3 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 3; Biological: Sodium Chloride 0.9%

Part B (Stage 2) - Group 4

EXPERIMENTAL

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

Biological: HSV 2 Formulation 3; Biological: HSV 2 Formulation 4; Biological: Sodium Chloride 0.9%

Part B (Stage 2) - Group 5

EXPERIMENTAL

HSV 2 Formulation 5 administered in one arm and Formulation 3 in the opposite arm, at Month 0 and Month 2

Biological: HSV 2 Formulation 3; Biological: HSV 2 Formulation 5

Part B (Stage 2) - Group 6

PLACEBO COMPARATOR

Sodium Chloride 0.9% (in both arms) at Month 0 and Month 2

Biological: Sodium Chloride 0.9%

Part B (Stage 2) - Group 7

EXPERIMENTAL

HSV 2 Formulation 6 administered concomitantly with 0.9% sodium chloride in the opposite arm at Month 0 and Month 2

Biological: HSV 2 Formulation 6; Biological: Sodium Chloride 0.9%

Interventions

HSV 2 Formulation 1 BIOLOGICAL

Route of administration: Intramuscular

Part A - Group 1; Part B (Stage 1) - Group 1; Part B (Stage 2) - Group 1

HSV 2 Formulation 2 BIOLOGICAL

Route of administration: Intramuscular

Part A - Group 2; Part B (Stage 1) - Group 2; Part B (Stage 2) - Group 2

HSV 2 Formulation 3 BIOLOGICAL

Route of administration: Intramuscular

Part A - Group 3; Part A - Group 4; Part A - Group 5; Part B (Stage 1) - Group 3; Part B (Stage 1) - Group 4; Part B (Stage 1) - Group 5; Part B (Stage 2) - Group 3; Part B (Stage 2) - Group 4; Part B (Stage 2) - Group 5

HSV 2 Formulation 4 BIOLOGICAL

Route of administration: Intramuscular

Part A - Group 4; Part B (Stage 1) - Group 4; Part B (Stage 2) - Group 4

HSV 2 Formulation 5 BIOLOGICAL

Route of administration: Intramuscular

Part A - Group 5; Part B (Stage 1) - Group 5; Part B (Stage 2) - Group 5

HSV 2 Formulation 6 BIOLOGICAL

Route of administration: Intramuscular

Part B (Stage 1) - Group 7; Part B (Stage 2) - Group 7

Sodium Chloride 0.9% BIOLOGICAL

Route of administration: Intramuscular

Part A - Group 1; Part A - Group 2; Part A - Group 3; Part A - Group 4; Part A - Group 6; Part B (Stage 1) - Group 1; Part B (Stage 1) - Group 2; Part B (Stage 1) - Group 3; Part B (Stage 1) - Group 4; Part B (Stage 1) - Group 6; Part B (Stage 1) - Group 7; Part B (Stage 2) - Group 1; Part B (Stage 2) - Group 2; Part B (Stage 2) - Group 3; Part B (Stage 2) - Group 4; Part B (Stage 2) - Group 6; Part B (Stage 2) - Group 7

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead
• Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): collaborator

Study Sites (4)

Research Centers of America-Site Number:8400010

Hollywood, Florida, 33024, United States

Location

Brigham and Womens Hospital-Site Number:8400003

Boston, Massachusetts, 02115, United States

Location

M3 Wake Research Inc-Site Number:8400006

Raleigh, North Carolina, 27612, United States

Location

University of Washington Virology Research Clinic-Site Number:8400001

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Herpes Genitalis

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 10, 2020
• Study Start: February 18, 2020
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: October 25, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

US (4)