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
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Phase
Phase 1/Phase 2
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Recruitment status
Completed
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Participants
505
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Lead sponsor
GlaxoSmithKline
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Start date
2022-03-07
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Number of sites
30
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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.
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Short title
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
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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
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2025-06-12
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First posted
2022-03-28
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Registry last updated
2025-09-08
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Primary completion date
2025-06-12
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Start date
2022-03-07
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Actual participants
505
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Participants
505
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Participant count basis
Actual
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Protocol amendments
10
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Number of sites
30
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
GlaxoSmithKline
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05298254
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ClinicalTrials.gov ID
NCT05298254
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masking description
Data will be collected in an observer-blind manner.
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Percentage of participants reporting each solicited administration site event

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

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

  2. Percentage of participants reporting each solicited administration site event

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

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

  3. Percentage of participants reporting each solicited systemic event

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

    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.

  4. Percentage of participants reporting each solicited systemic event

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

    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.

  5. Percentage of participants reporting unsolicited adverse events (AEs)

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

    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.

  6. Percentage of participants reporting unsolicited adverse events (AEs)

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

    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.

  7. Percentage of participants reporting medically attended events (MAEs)

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

    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.

  8. Percentage of participants reporting any serious adverse events (SAEs)

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

    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.

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

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

    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.

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

    Timeframe: At pre-study intervention administration (Day 1)

    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.

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

    Timeframe: At Day 8

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

    Timeframe: At Day 29

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

    Timeframe: At Day 36

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

    Timeframe: At Day 64

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

    Timeframe: At pre-study intervention administration (Day 1)

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

    Timeframe: At Day 8

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

    Timeframe: At Day 29

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

    Timeframe: At Day 36

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

    Timeframe: At Day 57

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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. 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.

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

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

    Duration in days (i.e., number of days with RGH-associated symptoms) of each genital herpes recurrence is displayed by arm group. 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.

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

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

    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. 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.

  6. HSV-2 shedding rate reduction from baseline to 6 weeks post-Dose 2 (Day 71) in Part II of the study

    Timeframe: At 6 weeks post-Dose 2 (Day 71) compared to baseline (Day -28 to Day -1)

    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.

  7. Number of HSV-2 DNA shedding episodes in Part II of the study

    Timeframe: Day -28 to Day -1

    Number of HSV-2 shedding episodes during the 28-day swabbing period.

  8. Number of HSV-2 DNA shedding episodes in Part II of the study

    Timeframe: Day 43 to Day 70

    Number of HSV-2 shedding episodes during the 28-day swabbing period.

  9. Number of HSV-2 DNA shedding episodes in Part II of the study

    Timeframe: Day 181 to Day 208

    Number of HSV-2 shedding episodes during the 28-day swabbing period.

  10. Duration of HSV-2 DNA shedding episodes in Part II of the study

    Timeframe: Day -28 to Day -1

    Number of days of a HSV-2 shedding episode.

  11. Duration of HSV-2 DNA shedding episodes in Part II of the study

    Timeframe: Day 43 to Day 70

    Number of days of a HSV-2 shedding episode.

  12. Duration of HSV-2 DNA shedding episodes in Part II of the study

    Timeframe: Day 181 to Day 208

    Number of days of a HSV-2 shedding episode.

  13. Anti-HSVTI antibody geometric mean concentrations (GMCs) in Part I of the study

    Timeframe: At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394

  14. Anti-HSVTI antibody geometric mean concentrations (GMCs) in Part II of the study

    Timeframe: At pre-study intervention administration (Day 1), Day 29 and Day 57

  15. Percentage of seropositive participants for anti-HSVTI antibodies in Part I of the study

    Timeframe: At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394

  16. Percentage of seropositive participants for anti-HSVTI antibodies in Part II of the study

    Timeframe: At pre-study intervention administration (Day 1), Day 29 and Day 57

  17. 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

    Timeframe: At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394

  18. 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

    Timeframe: At pre-study intervention administration (Day 1), Day 29 and Day 57

  19. 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

    Timeframe: At pre-study intervention administration (Day 1), Day 29, Day 64, Day 209 and Day 394

  20. 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

    Timeframe: At pre-study intervention administration (Day 1), Day 29 and Day 57

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults
Minimum age
18 Years
Maximum age
60 Years
Healthy volunteers
Yes

  • • 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.

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 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.
Sources for eligibility
clinicaltrials.gov

  • GSK Investigational SitePhoenix, United States
  • GSK Investigational SiteWichita, United States
  • GSK Investigational SiteKansas City, United States
  • GSK Investigational SiteRochester, United States
  • GSK Investigational SiteRichmond, United States
  • GSK Investigational SiteSeattle, United States
  • GSK Investigational SiteDarlinghurst, Australia
  • GSK Investigational SiteSydney, Australia
  • GSK Investigational SiteAntwerp, Belgium
  • GSK Investigational SiteBrussels, Belgium
  • GSK Investigational SiteEdegem, Belgium
  • GSK Investigational SiteGhent, Belgium
  • GSK Investigational SiteMontreal, Canada
  • GSK Investigational SiteTartu, Estonia
  • GSK Investigational SiteBerlin, Germany
  • GSK Investigational SiteBerlin, Germany
  • GSK Investigational SiteBochum, Germany
  • GSK Investigational SiteCologne, Germany
  • GSK Investigational SiteFrankfurt, Germany
  • GSK Investigational SiteHamburg, Germany
  • GSK Investigational SiteBarcelona, Spain
  • GSK Investigational SiteBarcelona, Spain
  • GSK Investigational SiteMadrid, Spain
  • GSK Investigational SiteMadrid, Spain
  • GSK Investigational SiteMadrid, Spain

And 5 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2021-003586-35
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (2)

Targets (14)