Last updated: 06/11/2026 10:20:16
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
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: The purpose of this first-time-in-human (FTiH) study was to evaluate the reactogenicity, safety, immune response, and efficacy of an investigational herpes simplex virus (HSV)-targeted immunotherapy (TI). The study was 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Part 1: Number of participants with solicited administration site events
Timeframe: Within 7 days post-dose (day of administration and 6 subsequent days after each dose; Dose 1 on Day 1 and Dose 2 on Day 29)
Part 2: Number of participants with solicited administration site events
Timeframe: Within 7 days post-dose (day of administration and 6 subsequent days after each dose; Dose 1 on Day 1 and Dose 2 on Day 29)
Part 1: Number of participants with solicited systemic events
Timeframe: Within 7 days post-dose (day of administration and 6 subsequent days after each dose; Dose 1 on Day 1 and Dose 2 on Day 29)
Part 2: Number of participants with solicited systemic events
Timeframe: Within 7 days post-dose (day of administration and 6 subsequent days after each dose; Dose 1 on Day 1 and Dose 2 on Day 29)
Part 1: Number of participants with unsolicited adverse events (AEs)
Timeframe: During 28 days after each dose (day of administration and 27 subsequent days after each dose; Dose 1 on Day 1 and Dose 2 on Day 29)
Part 2: Number of participants with unsolicited AEs
Timeframe: During 28 days after each dose (day of administration and 27 subsequent days after each dose; Dose 1 on Day 1 and Dose 2 on Day 29)
Part 1: Number of participants with Medically attended AEs (MAEs)
Timeframe: From Day 1 to Day 394
Part 2: Number of participants with MAEs
Timeframe: From Day 1 to Day 394
Part 1: Number of participants with Serious AEs (SAEs)
Timeframe: From Day 1 to Day 394
Part 2: Number of participants with SAEs
Timeframe: From Day 1 to Day 394
Part 1: Number of participants with potential immune-mediated diseases (pIMDs)
Timeframe: From Day 1 to Day 394
Part 2: Number of participants with pIMDs
Timeframe: From Day 1 to Day 394
Part 1: Number of participants with haematological and biochemical laboratory shifts at Day 8
Timeframe: At Day 8
Part 1: Number of participants with haematological and biochemical laboratory shifts at Day 29
Timeframe: At Day 29
Part 1: Number of participants with haematological and biochemical laboratory shifts at Day 36
Timeframe: At Day 36
Part 1: Number of participants with haematological and biochemical laboratory shifts at Day 64
Timeframe: At Day 64
Part 2: Number of participants with haematological and biochemical laboratory shifts at Day 8
Timeframe: At Day 8
Part 2: Number of participants with haematological and biochemical laboratory shifts at Day 29
Timeframe: At Day 29
Part 2: Number of participants with haematological and biochemical laboratory shifts at Day 36
Timeframe: At Day 36
Part 2: Number of participants with haematological and biochemical laboratory shifts at Day 57
Timeframe: At Day 57
Part 2: Time to first PCR confirmed HSV-2 Recurrent Genital Herpes (RGH) episode
Timeframe: From Day 43 [14 days post-Dose 2 (at Day 29)] to Day 209 (6 months post-Dose 2)
Secondary outcomes:
Part 2: Incidence Rate of PCR- confirmed HSV-2 RGH episodes
Timeframe: From Day 43 [14 days post-Dose 2 (at Day 29)] to Day 209 (6 months post-Dose 2)
Part 2: Number of participants free from confirmed HSV-2 RGH episode
Timeframe: From Day 43 [14 days post-Dose 2 (at Day 29)] to Day 209 (6 months post-Dose 2)
Part 2: Severity of RGH Episode‑Associated Symptoms During Each PCR Confirmed HSV-2 RGH Episode Assessed by Herpes Symptoms Checklist (HSC) Total Score
Timeframe: From Day 43 [14 days post-Dose 2 (at Day 29)] to Day 209 (6 months post-Dose 2)
Part 2: Duration of RGH-associated symptoms during each PCR confirmed HSV-2 RGH episode
Timeframe: From Day 43 [14 days post-Dose 2 (at Day 29)] to Day 209 (6 months post-Dose 2)
Part 2: Lesion rate of Confirmed HSV-2 Genital Herpes Episodes per Person-Year
Timeframe: From Day 43 [14 days post-Dose 2 (at Day 29)] to Day 209 (6 months post-Dose 2)
Part 2: HSV-2 shedding rate reduction
Timeframe: At 6 weeks post-Dose 2 (Day 43 to Day 71) compared to baseline (Day -28 to Day -1)
Part 2: Number of HSV-2 DNA shedding episodes
Timeframe: From start of the baseline (Day -28) up to Day -1
Part 2: Number of HSV-2 DNA shedding episodes
Timeframe: Day 43 to Day 70
Part 2: Duration of HSV-2 DNA shedding episodes
Timeframe: From start of the baseline (Day -28) up to Day -1
Part 2: Duration of HSV-2 DNA shedding episodes
Timeframe: Day 43 to Day 70
Part 1: Anti-Glycoprotein E/I (gE-gI) antibody geometric mean concentration (GMC)
Timeframe: At Day 1, Day 29, Day 64, Day 209 and Day 394
Part 2: Anti-gE-gI antibody GMC
Timeframe: At Day 1, Day 29 and Day 57
Part 1: Number of participants with HSV-2 gE-gI binding Immunoglobulin G (IgG) concentrations >= 0.99 EU/mL (seropositive rate), assessed by ELISA
Timeframe: At Day 1, Day 29, Day 64, Day 209 and Day 394
Part 2: Number of participants with HSV-2 gE-gI binding IgG concentrations >= 1.38 EU/mL (seropositive rate), assessed by ELISA
Timeframe: At Day 1, Day 29 and Day 57
Part 1: Geometric mean of polypositive gE-gI-specific Cluster of Differentiation (CD)4+ T-cells
Timeframe: At Day 1, Day 29, Day 64, Day 209 and Day 394
Part 2: Geometric mean of polypositive gE-gI-specific Cluster of Differentiation (CD)4+ T-cells
Timeframe: At Day 1, Day 29, and Day 57
Part 1: Geometric mean of polypositive gE-gI-specific CD8+ T-cells frequency
Timeframe: At Day 1, Day 29, Day 64, Day 209 and Day 394
Part 2: Geometric mean of polypositive gE-gI-specific CD8+ T-cells frequency
Timeframe: At Day 1, Day 29, and Day 57
Interventions:
Biological/vaccine: 40 µg gE-gI
Biological/vaccine: 80 µg gE-gI
Biological/vaccine: 160 µg gE-gI
Biological/vaccine: 40 µg gE-gI/AS01B
Biological/vaccine: 80 µg gE-gI/AS01B
Biological/vaccine: 60 µg gE-gI/AS01B
Biological/vaccine: 40 µg gE-gI/AS01E
Biological/vaccine: 80 µg gE-gI/AS01E
Biological/vaccine: 160 µg gE-gI/AS01E
Drug: Placebo
Enrollment:
504
Observational study model:
Not applicable
Primary completion date:
2025-12-06
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Herpes Simplex
Product
GSK3943104A
Collaborators
Not applicable
Study date(s)
March 2022 to June 2025
Type
Interventional
Phase
1/2
Participation criteria
Sex
Female & Male
Age
18 - 60 Years
Accepts healthy volunteers
Yes
- 1. Participants, who, in the opinion of the investigator, can and will comply with the requirements of the Protocol.
- 2. Written informed consent obtained from the participant prior to performance of any study-specific procedure.
- Medical Conditions
- 14. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, endocrine, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
Inclusion and exclusion criteria
Inclusion criteria:
- 1. Participants, who, in the opinion of the investigator, can and will comply with the requirements of the Protocol. 2. Written informed consent obtained from the participant prior to performance of any study-specific procedure. 3. Women of non-childbearing potential can be enrolled in the study. 4. 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. 5. 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. 6. 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. 7. Only for PART I: Man or woman aged 18 to 40 years, included, at the time of the first study intervention administration. 8. Only for PART I: Seronegative for HSV-2 as determined by Western blot performed at the Screening visit. 9. 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. 10. Only for PART II: Man or woman aged 18 to 60 years, included, at the time of the first study intervention administration. 11. 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. 12. 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. 13. 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. This criterion can only be checked at Visit 1 (Day 1).
Exclusion criteria:
- Medical Conditions 14. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, endocrine, or renal functional abnormality, as determined by physical examination or laboratory screening tests. 15. 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. 16. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention. 17. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. 18. Hypersensitivity to latex. 19. Recurrent history or uncontrolled neurological disorders or seizures. 20. 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. 21. Body mass index < 18 kg/m^2 or > 35 kg/m^2. 22. Past or current Guillain-Barré syndrome. 23. History of any form of ocular HSV infection, HSV-related erythema multiforme, or HSV-related neurological complications. Prior/Concomitant Therapy 24. 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. 25. 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. 26. Administration or planned administration of long-acting immune-modifying drugs at any time during the study period. 27. 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. 28. 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. 29. Prior receipt of another vaccine containing HSV antigens. 30. Only for PART II: Planned use of suppressive anti-HSV therapy from the Screening visit until the end of the study. 31. 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. 32. Only for PART II: Planned use of topical antiviral medication in the anogenital region from the Screening visit until the end of the study. 33. 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 34. 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 35. Pregnant or lactating women. 36. 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.
Trial location(s)
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2025-12-06
Actual study completion date
2025-12-06
Plain language summaries
Summary of results in plain language
Available language(s): English, Dutch (Belgium), Estonian, French (Belgium), French (Canadian), German, Spanish, Spanish (United States)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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