A Study on the Reactogenicity, Safety and Immune Response of a Targeted Immunotherapy Against HSV in Healthy Japanese Participants Aged 18-40 Years

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of 2 formulations of Herpes Simplex Virus (HSV)-Targeted Immunotherapy (HSVTI) in HSV-2 seronegative ethnic Japanese adults aged 18-40 years.

Official Title
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A Phase 1, Observer-blind, Randomized, Placebo-Controlled Study to Evaluate Reactogenicity, Safety and Immune Response of an HSV-targeted Immunotherapy in HSV-2 Seronegative Japanese Participants Aged 18-40 Years

Conditions
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Herpes Simplex

Intervention / Treatment
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* Biological: HSVTI Formulation 1
* Biological: HSVTI Formulation 2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits). Written informed consent obtained from the participant prior to performance of any study-specific procedure. Healthy participants as established by medical history and physical examination, at the discretion of the investigator, before entering into the study. Man or woman aged 18 to 40 years, included, at the time of screening. Japanese ethnic origin (defined as having been born in Japan with 4 ethnic Japanese grandparents and able to speak Japanese). Women of non-childbearing potential may be enrolled in the study. Women of childbearing potential may be enrolled in the study, if the participant: Has practiced highly effective contraception for 1 month prior to study intervention administration, and Has a negative pregnancy test result at the Screening visit and on the day of each study intervention administration, and Has agreed to continue highly effective contraception until Day 118, approximately 3 months post-Dose 2. Blood sample for simultaneous FSH and estradiol levels may be collected and tested locally at the discretion of the investigator to confirm non-reproductive potential according to local laboratory reference range. • Seronegative for HSV-2 as determined by Western blot performed at the Screening visit. Exclusion Criteria: Medical conditions: Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, endocrine, or renal functional abnormality, as determined by physical examination or laboratory screening tests. Clinically significant abnormalities may include but are not limited to: evidence of cardiac damage, heart failure categorized as class II or greater according to the New York Heart Association functional classification, heart valve disease, pulmonary uncontrolled persistent asthma despite treatment, uncontrolled diabetes, or disease or disorder that may put the participant at risk or influence study results. Participants with a controlled underlying chronic co-morbidity may be enrolled, provided there have been no changes to their medication within 3 months prior to the Screening visit. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study or that would interfere with the immunogenicity assessments planned in this study. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention. Any confirmed or suspected immunosuppressive or immunodeficient condition or documented or suspected HIV infection, based on medical history and physical examination (no laboratory testing required). Hypersensitivity to latex. Recurrent history of or uncontrolled neurological disorders or seizures. At the screening visit: hematological parameters (hemoglobin level, white blood cell, platelet) and/or biochemical parameters (ALT, AST, creatinine, blood urea nitrogen) outside the normal laboratory ranges, unless the laboratory abnormalities are considered not clinically significant by the investigator. Body mass index =18 kg/m2 or =35 kg/m2. History of any form of ocular HSV infection, HSV-related erythema multiforme, or HSV-related neurological complications (including meningitis, encephalitis, radiculopathy, myelitis). Prior/Concomitant therapy: Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention during the period beginning as of the Screening visit, or their planned use during the study period. Planned administration or administration of a vaccine* in the period starting 15 days* before each dose and ending 15 days* after each dose of study intervention administration**. * In case of adjuvanted and live-attenuated vaccines, this time window is to be increased to 30 days before and after each dose. In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced if, necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly. Administration or planned administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab). Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study intervention or planned administration during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose. For corticosteroids, this will mean prednisone equivalent =20 mg/day for adult participants. Inhaled, intra articular and topical steroids are allowed. Prior receipt of a vaccine containing HSV antigens. Prior/Concurrent clinical study experience: • Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug or invasive medical device). Other exclusions: • Pregnant or lactating woman. Woman planning to become pregnant or planning to discontinue contraceptive precautions before Day 118 (approximately 3 months post-Dose 2).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSVTI_F1 group<br>HSV-2 seronegative participants randomized in this group will receive 2 doses of HSVTI Formulation 1 of the study intervention at Day 1 and Day 29. | Biological: HSVTI Formulation 1<br>* This investigational intervention will be administered intramuscular as 2 doses to HSVTI_F1 Group.<br>|
| Experimental: HSVTI_F2 group<br>HSV-2 seronegative participants randomized in this group will receive 2 doses of HSVTI Formulation 2 of the study intervention at Day 1 and Day 29. | Biological: HSVTI Formulation 2<br>* This investigational intervention will be administered intramuscular as 2 doses to HSVTI_F2 Group.<br>|
| Placebo Comparator: Placebo group<br>HSV-2 seronegative participants randomized in this group will receive 2 doses of placebo as control at Day 1 and Day 29. | Biological: Placebo<br>* This intervention will be administered intramuscular as 2 doses to Placebo group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with solicited administration site events | Assessed solicited administration site events include redness, pain, and swelling. | Within 7 days post-study intervention administration (i.e., the day of intervention and 6 subsequent days, study intervention administered on Day 1 and Day 29) | 
| Percentage of participants with solicited systemic events | Assessed solicited systemic events included fever, myalgia, arthralgia, headache, and fatigue. | Within 7 days post-study intervention administration (i.e., the day of intervention and 6 subsequent days, study intervention administered on Day 1 and Day 29) | 
| Percentage of participants with unsolicited adverse events (AEs) | An unsolicited AE is an AE that was not included in the list of solicited events. Also, any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. | Within 28 days post-study intervention administration (i.e., the day of intervention and 27 subsequent days, study intervention administered on Day 1 and Day 29) | 
| Percentage of participants reporting Medically Attended Events (MAEs) | MAEs are defined as adverse events requiring medically-attended visits, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. | From Day 1 (dose 1) up to Day 57 (28 days post dose 2) | 
| Percentage of participants reporting Serious Adverse Events (SAEs) | A SAE is defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. | From Day 1 (dose 1) up to Day 57 (28 days post dose 2) | 
| Percentage of participants reporting any newly diagnosed Potential Immune-Mediated Diseases (pIMDs) | Potential immune-mediated diseases (pIMDs) are defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. | From Day 1 (dose 1) up to Day 57 (28 days post dose 2) | 
| Percentage of participants reporting any exacerbation of pre-existing pIMDs | Potential immune-mediated diseases (pIMDs) are defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. | From Day 1 (dose 1) up to Day 57 (28 days post dose 2) | 
| Percentage of participants reporting any hematological and biochemical laboratory abnormalities | The hematological and biochemical laboratory abnormalities will be assessed using a toxicity grading scale (where grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=potentially life-threatening). The hematological and biochemical laboratory parameters considered for this analysis are: hemoglobin, white blood cells increase and decrease, platelets decrease, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen. | At Day 1 (pre-dose 1), Day 8 and Day 29 post-dose 1, and Day 36 and Day 57 post-dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Herpes Simplex Virus Targeted Immunotherapy (HSVTI) antibody geometric mean concentration (GMC) | Anti-HSVTI antibody GMC will be measured in titers. | At Day 1 (pre-study intervention administration), Day 29 (28 days post-Dose 1), and Day 57 (28 days post-Dose 2) | 
| Seropositivity rate of anti-HSVTI antibody | The seropositivity rate of anti-HSVTI antibody will be Enzyme-Linked Immunosorbent Assay (ELISA) assessed and measured in ELISA Units pe milliliter (EU/mL). | At Day 1 (pre-study intervention administration), Day 29 (28 days post-Dose 1), and Day 57 (28 days post-Dose 2) | 
| Geometric mean of HSVTI-specific cluster of differentiation (CD)4+/CD8+ T cells frequency | The geometric mean of HSVTI CD4+/CD8+ T cells frequency will be assessed to cells expressing at least 2 activation markers (Interferon [IFN]-gamma, Tumour necrosis factor [TNF]-alpha, Interleukin [IL]-2, IL-13, IL-17, 4-1BB and/or CD40L) and including at least one cytokine (assessed by cell glow cytometry [CFC]). | At Day 1 (pre-study intervention administration), Day 29 (28 days post-Dose 1), and Day 57 (28 days post-Dose 2) | 
| Percentage of participants reporting MAEs | MAEs are defined as adverse events requiring medically-attended visits, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. | From Day 1 (dose 1) up to Day 209 (end of study) | 
| Percentage of participants reporting SAEs | A SAE is defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. | From Day 1 (dose 1) up to Day 209 (end of study) | 
| Percentage of participants reporting any newly diagnosed Potential Immune-Mediated Diseases (pIMDs) | Potential immune-mediated diseases (pIMDs) are defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. | From Day 1 (dose 1) up to Day 209 (end of study) | 
| Percentage of participants reporting any exacerbation of pre-existing pIMDs | Potential immune-mediated diseases (pIMDs) are defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. | From Day 1 (dose 1) up to Day 209 (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herpes Simplex Virus genital herpes, Herpes Simplex Virus, Reactogenicity, Safety, Immune response