A Study on the Reactogenicity, Safety, Immune Response, and Efficacy of a Targeted Immunotherapy Against HSV in Healthy Participants Aged 18-40 Years or in Participants Aged 18-60 Years With Recurrent Genital Herpes

NCT05298254 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2153362021-003586-35
• Study Type: interventional
• Target: 505
• Locations: 7 countries
• Sites: 24

Brief Summary

The purpose of this first-time-in-human (FTiH) study is to evaluate the reactogenicity, safety, immune response, and efficacy of an investigational herpes simplex virus (HSV)-targeted immunotherapy (TI). The study will be conducted in 2 parts: Part I assessing different formulations of the Herpes Simplex Virus-targeted immunotherapy (HSVTI) in healthy participants aged 18-40 years; Part II assessing the 2 formulations of the HSVTI in participants aged 18-60 years with recurrent genital herpes.

Conditions

Herpes Simplex

Keywords

First Time in Human; Healthy participants; Recurrent genital herpes; Herpes Simplex Virus; Reactogenicity; Safety; Immune response; Efficacy

Outcome Measures

Primary Outcomes (20)

• Percentage of participants reporting each solicited administration site event

  The solicited administration site events are pain, redness and swelling.

  Within 7 days after the first study intervention dose (administered at Day 1)

• Percentage of participants reporting each solicited administration site event

  The solicited administration site events are pain, redness and swelling.

  Within 7 days after the second study intervention dose (administered at Day 29)

• Percentage of participants reporting each solicited systemic event

  The solicited systemic events are fever, fatigue, headache, myalgia and arthralgia. The preferred location for measuring temperature is the oral cavity. Fever is defined as temperature equal to or above (≥) 38.0 degree Celsius (°C)/ 100.4 degree Fahrenheit (°F), regardless the location of measurement.

  Within 7 days after the first study intervention dose (administered at Day 1)

• Percentage of participants reporting each solicited systemic event

  The solicited systemic events are fever, fatigue, headache, myalgia and arthralgia. The preferred location for measuring temperature is the oral cavity. Fever is defined as temperature equal to or above (≥) 38.0 degree Celsius (°C)/ 100.4 degree Fahrenheit (°F), regardless the location of measurement.

  Within 7 days after the second study intervention dose (administered at Day 29)

• Percentage of participants reporting unsolicited adverse events (AEs)

  An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms (7 days after each dose) is reported as an unsolicited AE.

  Within 28 days after the first study intervention dose (administered at Day 1)

• Percentage of participants reporting unsolicited adverse events (AEs)

  An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms (7 days after each dose) is reported as an unsolicited AE.

  Within 28 days after the second study intervention dose (administered at Day 29)

• Percentage of participants reporting medically attended events (MAEs)

  An MAE is an unsolicited AE for which the participants received medical attention defined as any symptoms or illnesses requiring hospitalization, or an emergency room visit, or visit to/by healthcare professionals.

  From Dose 1 (Day 1) up 12 months after last study intervention administration (Day 394)

• Percentage of participants reporting any serious adverse events (SAEs)

  An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes.

  From Dose 1 (Day 1) up to 12 months after last study intervention administration (Day 394)

• Percentage of participants reporting any potential immune-mediated disease (pIMDs) (classified as newly diagnosed or exacerbation of pre-existing events)

  PIMDs are a subset of adverse events of special interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  From Dose 1 (Day 1) up to 12 months after last study intervention administration (Day 394)

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at pre-study intervention administration (Day 1) in Part I of the study

  Clinically significant haematological and biochemical abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

  At pre-study intervention administration (Day 1)

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part I of the study

  At Day 8

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in Part I of the study

  At Day 29

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part I of the study

  At Day 36

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 64 in Part I of the study

  At Day 64

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at pre-study intervention administration (Day 1) in Part II of the study

  At pre-study intervention administration (Day 1)

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part II of the study

  At Day 8

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in part II of the study

  At Day 29

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part II of the study

  At Day 36

• Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 57 in Part II of the study

  At Day 57

• Time-to-first confirmed HSV-2 RGH episode in Part II of the study

  A suspected RGH episode will be classified as confirmed HSV-2 RGH episode if at least one of the lesional or anogenital swabs taken during the concerned episode is positive for HSV-2 as measured by PCR. The end of RGH reporting can occur at Day 209 for participants who have not yet completed Visit 8 \[Day 209\] at the time the Informed Consent Form (ICF) addendum was signed and consented, or at non-scheduled time, being defined by the date on which participants decided to stop the RGH reporting after acknowledgement of unsuccessful primary analysis before ICF addendum consent or the day the eDiary is deactivated after ICF addendum consent.

  14 days post-Dose 2 (Day 43) to end of RGH event reporting period

Secondary Outcomes (20)

• Number of confirmed HSV-2 RGH episodes in Part II of the study

  14 days post-Dose 2 (Day 43) to end of RGH event reporting period

• Percentage of participants free from confirmed HSV-2 RGH episode in Part II of the study

  At 6 months after the last study intervention administration (Day 29)

• Herpes Symptoms Checklist (HSC) total score during each confirmed HSV-2 RGH episode in Part II of the study

  14 days post-Dose 2 (Day 43) to end of RGH event reporting period

• Number of days with RGH-associated symptoms during each confirmed HSV-2 RGH episode in Part II of the study

  14 days post-Dose 2 (Day 43) to end of RGH event reporting period

• Number of days with confirmed HSV-2 genital herpes lesions in Part II of the study

  14 days post-Dose 2 (Day 43) to end of RGH event reporting period

Study Arms (13)

Non-adjuvanted HSV formulation 1 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the non-adjuvanted HSV formulation 1 vaccine, one at Day 1 and one at Day 29.

Biological: Non-adjuvanted HSV formulation 1

Non-adjuvanted HSV formulation 2 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the non-adjuvanted HSV formulation 2 vaccine, one at Day 1 and one at Day 29.

Biological: Non-adjuvanted HSV formulation 2

Non-adjuvanted HSV formulation 3 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the non-adjuvanted HSV formulation 3 vaccine, one at Day 1 and one at Day 29.

Biological: Non-adjuvanted HSV formulation 3

HSV formulation 1 with adjuvant 1 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 1 with adjuvant 1 vaccine, one at Day 1 and one at Day 29.

Biological: HSV formulation 1 with adjuvant 1

HSV formulation 2 with adjuvant 1 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 2 with adjuvant 1 vaccine, one at Day 1 and one at Day 29.

Biological: HSV formulation 2 with adjuvant 1

HSV formulation 3 with adjuvant 1 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 3 with adjuvant 1 vaccine, one at Day 1 and one at Day 29.

Biological: HSV formulation 3 with adjuvant 1

HSV formulation 1 with adjuvant 2 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 1 with adjuvant 2 vaccine, one at Day 1 and one at Day 29.

Biological: HSV formulation 1 with adjuvant 2

HSV formulation 2 with adjuvant 2 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 2 with adjuvant 2 vaccine, one at Day 1 and one at Day 29.

Biological: HSV formulation 2 with adjuvant 2

HSV formulation 3 with adjuvant 2 - Part I Group

EXPERIMENTAL

Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 3 with adjuvant 2 vaccine, one at Day 1 and one at Day 29.

Biological: HSV formulation 3 with adjuvant 2

Placebo - Part I Group

PLACEBO COMPARATOR

Participants enrolled in Part I of the study who receive 2 doses of Placebo, one at Day 1 and one at Day 29.

Drug: Placebo

HSVTI formulation (F) 1 - Part II Group

EXPERIMENTAL

Participants enrolled in Part II of the study who receive 2 doses of the formulation of the HSVTI\_F1 selected from Part I of the study, one at Day 1 and one at Day 29.

Biological: HSVTI_F1

HSVTI_F2 - Part II Group

EXPERIMENTAL

Participants enrolled in Part II of the study who receive 2 doses of the HSVTI\_F2 selected from Part I of the study, one at Day 1 and one at Day 29.

Biological: HSVTI_F2

Placebo - Part II Group

PLACEBO COMPARATOR

Participants enrolled in Part II of the study who receive 2 doses of Placebo, one at Day 1 and one at Day 29.

Drug: Placebo

Interventions

Non-adjuvanted HSV formulation 1 BIOLOGICAL

Two doses of the non-adjuvanted HSV formulation 1 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

Non-adjuvanted HSV formulation 1 - Part I Group

Non-adjuvanted HSV formulation 2 BIOLOGICAL

Two doses of the non-adjuvanted HSV formulation 2 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

Non-adjuvanted HSV formulation 2 - Part I Group

Non-adjuvanted HSV formulation 3 BIOLOGICAL

Two doses of the non-adjuvanted HSV formulation 3 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

Non-adjuvanted HSV formulation 3 - Part I Group

HSV formulation 1 with adjuvant 1 BIOLOGICAL

Two doses of the HSV formulation 1 with adjuvant 1 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

HSV formulation 1 with adjuvant 1 - Part I Group

HSV formulation 2 with adjuvant 1 BIOLOGICAL

Two doses of the HSV formulation 2 with adjuvant 1 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

HSV formulation 2 with adjuvant 1 - Part I Group

HSV formulation 3 with adjuvant 1 BIOLOGICAL

Two doses of the HSV formulation 3 with adjuvant 1 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

HSV formulation 3 with adjuvant 1 - Part I Group

HSV formulation 1 with adjuvant 2 BIOLOGICAL

Two doses of the HSV formulation 1 with adjuvant 2 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

HSV formulation 1 with adjuvant 2 - Part I Group

HSV formulation 2 with adjuvant 2 BIOLOGICAL

Two doses of the HSV formulation 2 with adjuvant 2 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

HSV formulation 2 with adjuvant 2 - Part I Group

HSV formulation 3 with adjuvant 2 BIOLOGICAL

Two doses of the HSV formulation 3 with adjuvant 2 vaccine administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I of the study.

HSV formulation 3 with adjuvant 2 - Part I Group

Placebo DRUG

Two doses of Placebo administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part I and Part II of the study.

Placebo - Part I Group; Placebo - Part II Group

HSVTI_F1 BIOLOGICAL

Two doses of the formulation of the HSVTI\_F1 selected from Part I of the study administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part II of the study.

HSVTI formulation (F) 1 - Part II Group

HSVTI_F2 BIOLOGICAL

Two doses of the formulation of the HSVTI\_F2 selected from Part I of the study administered intramuscularly in the deltoid region of the non-dominant arm, one each at Day 1 and Day 29, during Part II of the study.

HSVTI_F2 - Part II Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the Protocol.
• Written informed consent obtained from the participant prior to performance of any study-specific procedure.
• Women of non-childbearing potential can be enrolled in the study.
• Women of childbearing potential can be enrolled in the study, if the participant:
• Has practiced highly effective contraception for one 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,
• For PART I: Has agreed to continue highly effective contraception until the end of the study.
• For PART II: Has agreed to continue highly effective contraception until 3 months after last study intervention administration.
• Seronegative for human immunodeficiency virus (HIV), as determined by laboratory screening tests. Participants documented to be seropositive to HIV will not be eligible for study participation.
• Only for PART I: Healthy participants as established by medical history and physical examination, at the discretion of the investigator, before entering into the study.
• Only for PART I: Man or woman aged 18 to 40 years, included, at the time of the first study intervention administration.
• Only for PART I: Seronegative for HSV-2 as determined by Western blot performed at the Screening visit.
• Only for PART II: Participants with recurrent genital herpes and with no significant health problems as established by medical history and physical examination, at the discretion of the investigator, before entering the study.
• Diagnosis of genital herpes for at least one year before the Screening visit.
• History of self-reported or documented recurrent lesional genital herpes frequency of at least 3 and no more than 9 reported clinical recurrences in the 12 months preceding the screening visit, or, if still on suppressive therapy within 3 months before the Screening visit, prior to initiation of suppressive therapy.

You may not qualify if:

• Medical Conditions
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, endocrine, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• 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 efficacy and 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, based on medical history and physical examination.
• Hypersensitivity to latex.
• Recurrent history or uncontrolled neurological disorders or seizures.
• Haematological and/or biochemical parameters outside the normal laboratory ranges at the Screening visit, unless the laboratory abnormalities are considered not clinically significant by the investigator.
• Body mass index =\<18 kg/m\^2 or \>=35 kg/m\^2.
• Past or current Guillain-Barré syndrome.
• History of any form of ocular HSV infection, HSV-related erythema multiforme, or HSV-related neurological complications.
• Prior/Concomitant Therapy
• Use of any investigational or non-registered product other than the study intervention during the period beginning as of the Screening visit, or planned use during the study period.
• Planned administration/administration of a vaccine not foreseen by the Protocol in the period starting 15 days before each dose and ending 15 days after each dose of study intervention administration.
• Administration or planned administration of long-acting immune-modifying drugs at any time during the study period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (30)

GSK Investigational Site

Phoenix, Arizona, 85015, United States

Location

GSK Investigational Site

Wichita, Kansas, 67207, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64114, United States

Location

GSK Investigational Site

Rochester, New York, 14609, United States

Location

GSK Investigational Site

Richmond, Virginia, 23219, United States

Location

GSK Investigational Site

Seattle, Washington, 98105, United States

Location

GSK Investigational Site

Darlinghurst, New South Wales, 2010, Australia

Location

GSK Investigational Site

Sydney, New South Wales, 2010, Australia

Location

GSK Investigational Site

Antwerp, 2000, Belgium

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

Location

GSK Investigational Site

Tartu, 50106, Estonia

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, 10439, Germany

Location

GSK Investigational Site

Bochum, 44787, Germany

Location

GSK Investigational Site

Cologne, 50674, Germany

Location

GSK Investigational Site

Frankfurt, 60596, Germany

Location

GSK Investigational Site

Hamburg, 20146, Germany

Location

GSK Investigational Site

Barcelona, 08001, Spain

Location

GSK Investigational Site

Barcelona, 08015, Spain

Location

GSK Investigational Site

Madrid, 28010, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28222, Spain

Location

GSK Investigational Site

Marbella, 29600, Spain

Location

GSK Investigational Site

Brighton, BN2 1ES, United Kingdom

Location

GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

Location

GSK Investigational Site

London, WC1E 6JB, United Kingdom

Location

GSK Investigational Site

Southampton, SO14 0YG, United Kingdom

Location

MeSH Terms

Conditions

Herpes Simplex; Herpes Genitalis

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data will be collected in an observer-blind manner.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 28, 2022
• Study Start: March 7, 2022
• Primary Completion: June 12, 2025
• Study Completion: June 12, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

ES (1); GB (4); DE (6); AU (2); BE (4); US (6); CA (1)