Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of 4 Investigational HSV 2 Vaccines in Adults With Recurrent Genital Herpes Caused by HSV 2 (HSV15)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04222985
Recruitment Status : Active, not recruiting
First Posted : January 10, 2020
Last Update Posted : November 27, 2020
Sponsor:
Collaborator:
Immune Design
Information provided by (Responsible Party):
Sanofi ( 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

Condition or disease Intervention/treatment Phase
Genital Herpes Biological: HSV 2 Formulation 1 Biological: HSV 2 Formulation 2 Biological: HSV 2 Formulation 3 Biological: HSV 2 Formulation 4 Biological: HSV 2 Formulation 5 Biological: HSV 2 Formulation 6 Biological: Sodium Chloride 0.9% Phase 1 Phase 2

Detailed Description:
Study duration per participant is approximately 16 months

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 381 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 11, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Genital Herpes

Arm Intervention/treatment
Experimental: Part A - Group 1
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part A - Group 2
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part A - Group 3
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part A - Group 4
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
Route of administration: Intramuscular

Biological: HSV 2 Formulation 4
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part A - Group 5
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
Route of administration: Intramuscular

Biological: HSV 2 Formulation 5
Route of administration: Intramuscular

Placebo Comparator: Part A - Group 6
Sodium chloride 0.9% (in both arms) at Month 0 and Month 2
Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 1) - Group 1
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 1) - Group 2
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 1) - Group 3
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 1) - Group 4
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
Route of administration: Intramuscular

Biological: HSV 2 Formulation 4
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 1) - Group 5
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
Route of administration: Intramuscular

Biological: HSV 2 Formulation 5
Route of administration: Intramuscular

Placebo Comparator: Part B (Stage 1) - Group 6
Sodium Chloride 0.9% (in both arms) at Month 0 and Month 2
Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 1) - Group 7
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 2) - Group 1
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 2) - Group 2
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 2) - Group 3
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 2) - Group 4
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
Route of administration: Intramuscular

Biological: HSV 2 Formulation 4
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 2) - Group 5
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
Route of administration: Intramuscular

Biological: HSV 2 Formulation 5
Route of administration: Intramuscular

Placebo Comparator: Part B (Stage 2) - Group 6
Sodium Chloride 0.9% (in both arms) at Month 0 and Month 2
Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular

Experimental: Part B (Stage 2) - Group 7
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
Route of administration: Intramuscular

Biological: Sodium Chloride 0.9%
Route of administration: Intramuscular




Primary Outcome Measures :
  1. Number of participants with immediate adverse events [ Time Frame: Within 4 hours (participants in Part A) or 30 minutes (participants in Part B) after vaccination ]
    Unsolicited systemic adverse events occurring immediately after vaccination

  2. Number of participants with solicited injection site and systemic reactions [ Time Frame: Within 7 days after vaccination ]
    Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills

  3. Number of participants with unsolicited adverse events [ Time Frame: Within 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

  4. Number of participants with medically-attended adverse events (MAAEs) [ Time Frame: 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

  5. Number of participants with adverse events of special interest (AESIs) [ Time Frame: From Day 0 to Month 14 ]
    AESIs are collected throughout the study

  6. Number of participants with serious adverse events (SAEs) [ Time Frame: From Screening to Month 14 ]
    SAEs are collected throughout the study

  7. Number of participants with out-of-range biological test results [ Time Frame: From 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

  8. Viral genital shedding rate [ Time Frame: 60 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

  9. Genital HSV recurrence [ Time Frame: 6 months following the second vaccination ]
    Proportion of participants free of genital HSV recurrence following the second vaccination


Secondary Outcome Measures :
  1. Genital lesion rate [ Time Frame: 6 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

  2. Genital HSV recurrence [ Time Frame: 60 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

  3. Viral genital shedding rate after the first and second vaccination [ Time Frame: 60 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

  4. Viral genital shedding rate after the first vaccination [ Time Frame: 60 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

  5. Change in serum HSV 2-antibody levels [ Time Frame: Before 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

  6. Change in level of HSV 2-specific cellular immune responses [ Time Frame: Before 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04222985


Locations
Layout table for location information
United States, Florida
Investigational Site Number 8400010
Hollywood, Florida, United States, 33024
United States, Massachusetts
Investigational Site Number 8400003
Boston, Massachusetts, United States, 02115
United States, North Carolina
Investigational Site Number 8400006
Raleigh, North Carolina, United States, 27612
United States, Washington
Investigational Site Number 8400001
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Immune Design
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi Pasteur, a Sanofi Company
Layout table for additonal information
Responsible Party: Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier: NCT04222985    
Other Study ID Numbers: HSV15
U1111-1183-6522 ( Other Identifier: UTN )
First Posted: January 10, 2020    Key Record Dates
Last Update Posted: November 27, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Herpes Genitalis
Herpes Simplex
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases