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

Herpes Simplex Clinical Trial

Official title:

A Phase I/II, Observer-blind, Randomised, Placebo-controlled, Multi-country Study to Evaluate Reactogenicity, Safety, Immune Response, and Efficacy of an HSV-targeted Immunotherapy in Healthy Participants Aged 18-40 Years or in Participants Aged 18-60 Years With Recurrent Genital Herpes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05298254
• Other study ID #: 215336
• Secondary ID: 2021-003586-35
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 7, 2022
• Est. completion date: July 5, 2026

Study information

• Verified date: April 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 342
• Est. completion date: July 5, 2026
• Est. primary completion date: July 3, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• • 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.

• Only for PART II: Man or woman aged 18 to 60 years, included, at the time of the first study intervention administration.

• Only for PART II: Seropositive for HSV-2 as determined by serological testingperformed at the Screening visit, or having documented laboratory-confirmed HSV 2 genital herpes (i.e., HSV-2 DNA positive by a molecular technique such as polymerase chain reaction [PCR], or HSV-2 seropositive by a type-specific serology assay such as Western Blot or other immunoassay).Only for PART II (shedding sub-cohort): Participants agreeing to collect 2 swabs per day from anogenital area for the full duration of the 5 swabbing periods planned in the study.

• Only for PART II (shedding sub-cohort) after baseline completion: Participants having collected at least 45 out of 56 anogenital swabs during the baseline period.

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.

• 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.

• 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 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, or equivalent. Inhaled, intra articular and topical steroids are allowed.

• Prior receipt of another vaccine containing HSV antigens.

• Only for PART II: Planned use of suppressive anti-HSV therapy from the Screening visit until the end of the study.

• Only for PART II: Planned use of tenofovir therapy, or other medication known to affect HSV shedding or genital lesions from the Screening visit until the end of the study. Only for PART II: Planned use of topical antiviral medication in the anogenital region from the Screening visit until the end of the study.

• Only for PART II: Planned use of any episodic antiviral medications during the 5 swabbing periods (including the baseline period) (only for the shedding sub-cohort).

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.

Other Exclusions

• Pregnant or lactating women.

• Woman planning to become pregnant or planning to discontinue contraceptive precautions in the period starting from the Screening visit up to 3 months post-last dose of study intervention.

Related Conditions & MeSH terms

• Herpes Genitalis
• Herpes Simplex

Intervention

Biological:
• Non-adjuvanted HSV formulation 1
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 2
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 3
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.
• HSV formulation 1 with adjuvant 1
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 2 with adjuvant 1
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 3 with adjuvant 1
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 1 with adjuvant 2
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 2 with adjuvant 2
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 3 with adjuvant 2
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.

Drug:
• Placebo
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.

Biological:
• HSVTI_F1
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_F2
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.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Darlinghurst, Sydney	New South Wales
Australia	GSK Investigational Site	Sydney	New South Wales
Belgium	GSK Investigational Site	Antwerpen
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Edegem
Belgium	GSK Investigational Site	Gent
Canada	GSK Investigational Site	Montreal	Quebec
Estonia	GSK Investigational Site	Tartu
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda	Madrid
Spain	GSK Investigational Site	Marbella
United Kingdom	GSK Investigational Site	Brighton	East Sussex
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Southampton
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Estonia,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part I of the study		At Day 8
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in Part I of the study		At Day 29
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part I of the study		At Day 36
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 64 in Part I of the study		At Day 64
Primary	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)
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part II of the study		At Day 8
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in part II of the study		At Day 29
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part II of the study		At Day 36
Primary	Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 57 in Part II of the study		At Day 57
Primary	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.	14 days post-Dose 2 (Day 43) to Day 759
Secondary	Number of confirmed HSV-2 RGH episodes 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.	14 days post-Dose 2 (Day 43) to Day 759
Secondary	Percentage of participants free from 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.	At 6, 12, 18 and 24 months after the last study intervention administration (Day 29)
Secondary	Herpes Symptoms Checklist (HSC) total score during each confirmed HSV-2 RGH episode in Part II of the study	During genital herpes recurrences, participants are asked to complete the HSC, a 13-item checklist of herpes symptoms, where respondents record the severity of symptoms on a 4-point scale where 0 indicates no symptom and a higher point for more symptoms and severity. Total scores range from 0 (no symptom) to 39 (severe symptoms). At the onset of the genital herpes recurrence, this questionnaire is to be completed once daily, until no lesions or symptoms are present.	14 days post-Dose 2 (Day 43) to Day 759
Secondary	Number of days with RGH-associated symptoms during each confirmed HSV-2 RGH episode in Part II of the study	Duration in days (i.e., number of days with RGH-associated symptoms) of each genital herpes recurrence is displayed by arm group.	14 days post-Dose 2 (Day 43) to Day 759
Secondary	Number of days with confirmed HSV-2 genital herpes lesions in Part II of the study	Number of days on which lesions (swelling, blisters, sores, or crusts) are reported by the participant in the anogenital area during confirmed RGH episodes divided by the number of days of follow-up.	14 days post-Dose 2 (Day 43) to Day 759
Secondary	HSV-2 shedding rate reduction from baseline to 6 weeks post-Dose 2 (Day 71) in Part II of the study	The HSV-2 shedding rate reduction is calculated as 1- (the HSV-2 shedding rate one month post-Dose 2 divided by the baseline HSV-2 shedding rate)*100.	At 6 weeks post-Dose 2 (Day 71) compared to baseline (Day -28 to Day -1)
Secondary	HSV-2 shedding rate reduction from baseline to 6 months post-Dose 2 (Day 209) in Part II of the study	The HSV-2 shedding rate reduction is calculated as 1 - (the HSV-2 shedding rate 6 months post-Dose 2 divided by the baseline HSV-2 shedding rate)*100.	At 6 months post-Dose 2 (Day 209) compared to baseline (Day -28 to Day -1)
Secondary	HSV-2 shedding rate reduction from baseline to 12 months post-Dose 2 (Day 394) in Part II of the study	The HSV-2 shedding rate reduction is calculated as 1 - (the HSV-2 shedding rate 12 months post-Dose 2 divided by the baseline HSV-2 shedding rate)*100.	At 12 months post-Dose 2 (Day 394) compared to baseline (Day -28 to Day -1)
Secondary	HSV-2 shedding rate reduction from baseline to 24 months post-Dose 2 (Day 759) in Part II of the study	The HSV-2 shedding rate reduction is calculated as 1 - (the HSV-2 shedding rate 24 months post-Dose 2 divided by the baseline HSV-2 shedding rate)*100.	At 24 months post-Dose 2 (Day 759) compared to baseline (Day -28 to Day -1)
Secondary	Number of HSV-2 DNA shedding episodes in Part II of the study	Number of HSV-2 shedding episodes during the 28-day swabbing period.	Day -28 to Day -1
Secondary	Number of HSV-2 DNA shedding episodes in Part II of the study	Number of HSV-2 shedding episodes during the 28-day swabbing period.	Day 43 to Day 70
Secondary	Number of HSV-2 DNA shedding episodes in Part II of the study	Number of HSV-2 shedding episodes during the 28-day swabbing period.	Day 181 to Day 208
Secondary	Number of HSV-2 DNA shedding episodes in Part II of the study	Number of HSV-2 shedding episodes during the 28-day swabbing period.	Day 366 to Day 393
Secondary	Number of HSV-2 DNA shedding episodes in Part II of the study	Number of HSV-2 shedding episodes during the 28-day swabbing period.	Day 731 to Day 758
Secondary	Duration of HSV-2 DNA shedding episodes in Part II of the study	Number of days of a HSV-2 shedding episode.	Day -28 to Day -1
Secondary	Duration of HSV-2 DNA shedding episodes in Part II of the study	Number of days of a HSV-2 shedding episode.	Day 43 to Day 70
Secondary	Duration of HSV-2 DNA shedding episodes in Part II of the study	Number of days of a HSV-2 shedding episode.	Day 181 to Day 208
Secondary	Duration of HSV-2 DNA shedding episodes in Part II of the study	Number of days of a HSV-2 shedding episode.	Day 366 to Day 393
Secondary	Duration of HSV-2 DNA shedding episodes in Part II of the study	Number of days of a HSV-2 shedding episode.	Day 731 to Day 758
Secondary	Anti-HSVTI antibody geometric mean concentrations (GMCs) in Part I of the study		At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394
Secondary	Anti-HSVTI antibody geometric mean concentrations (GMCs) in Part II of the study		At pre-study intervention administration (Day 1), Day 29, Day 57, Day 209 and Day 394, Day 574, and Day 759
Secondary	Percentage of seropositive participants for anti-HSVTI antibodies in Part I of the study		At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394
Secondary	Percentage of seropositive participants for anti-HSVTI antibodies in Part II of the study		At pre-study intervention administration (Day 1), Day 29, Day 57, Day 209 and Day 394, Day 574, and Day 759
Secondary	Geometric mean of HSVTI-specific Cluster of Differentiation (CD)4+ T-cells frequency expressing at least two activation markers and including at least one cytokine in Part I of the study		At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394
Secondary	Geometric mean of HSVTI-specific CD4+ T-cells frequency expressing at least 2 activation markers and including at least 1 cytokine in Part II of the study		At pre-study intervention administration (Day 1), Day 29, Day 57, Day 209 and Day 394, Day 574, and Day 759
Secondary	Geometric mean of HSVTI-specific CD8+ T-cells frequency expressing at least two activation markers and including at least one cytokine in Part I of the study		At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394
Secondary	Geometric mean of HSVTI-specific CD8+ T-cells frequency expressing at least 2 activation markers and including at least 1 cytokine in Part II of the study		At pre-study intervention administration (Day 1), Day 29, Day 57, Day 209 and Day 394, Day 574, and Day 759
Secondary	Percentage of participants with a fatal SAE, SAE related to study intervention and potential immune-mediated disease (pIMDs) related to study intervention in Part II of the study	A SAE related to study intervention is an SAE judged by the investigator as related to the study intervention. A fatal SAE is any untoward medical occurrence that results in death.	From Dose 1 (Day 1) up to study end (Day 759)