Evaluation of Reactogenicity, Safety, Immunogenicity, and Efficacy of HSV-Targeted Immunotherapy GSKVX000000030810 in Adults with Recurrent Genital Herpes

Trial ID: 2024-510571-37-00
Protocol: 215336
Sponsor: GlaxoSmithKline Biologicals

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Diseases & Conditions

Herpes simplex

Objectives

The primary objective of this study is to evaluate the **reactogenicity** and safety of the HSV-targeted immunotherapy (HSVTI) in participants. Additionally, for Part II of the study, the primary objective extends to demonstrating the efficacy of HSVTI in reducing the risk of confirmed HSV-2 recurrent genital herpes (RGH) episodes. This is clinically relevant as it addresses both the safety profile and potential therapeutic benefits of HSVTI in managing Herpes Simplex, a condition with significant morbidity due to recurrent episodes.

Secondary objectives include:

Evaluating the humoral and cellular immune responses induced by HSVTI.
Comparing HSVTI to placebo in terms of incidence rate of RGH episodes, percentage of RGH-free participants at 6 months post-intervention, severity and duration of RGH episode-associated symptoms, and lesion rate post-administration.
Assessing the effect of HSVTI on shedding rate approximately 6 weeks after the last dose, and evaluating HSV shedding in a specific sub-cohort.

Participants

The clinical trial involves a total of **108 participants** diagnosed with **Herpes Simplex**. The study population includes both male and female subjects, with an age range of 18 to 60 years. Participants were selected based on their ability to comply with the study protocol, including completion of an eDiary and attendance at follow-up visits. The trial includes individuals who are seropositive for HSV-2, as determined by serological testing, or have documented laboratory-confirmed HSV-2 genital herpes. Participants are required to be seronegative for HIV and must not belong to a vulnerable population. The study population is composed of individuals who are generally healthy, as established by medical history and physical examination, and who have no significant health problems. Lifestyle considerations such as diet and physical activity are not specified in the trial data. The trial does not include any vulnerable populations, ensuring a focus on individuals who can provide informed consent and adhere to the study requirements.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the reactogenicity, safety, immune response, and efficacy of an HSV-targeted immunotherapy in participants. The trial is divided into two parts, with Part I focusing on healthy participants aged 18-40 years and Part II on participants aged 18-60 years with recurrent **genital herpes**. The trial is expected to run from March 2022 to July 2025, with participant involvement lasting up to 12 months after the last study intervention administration.

Participants will undergo a series of study visits, beginning with a screening visit to assess eligibility based on inclusion criteria such as age, health status, and serological testing for HSV-2. Following successful screening, participants will be randomized to receive either the investigational product or a placebo, administered as a **suspension for injection** via **intramuscular use**. The study includes multiple follow-up visits to monitor safety and efficacy endpoints, including the percentage of participants reporting solicited and unsolicited adverse events, as well as laboratory abnormalities.

The primary endpoints focus on the percentage of participants reporting administration site and systemic events, as well as serious adverse events (SAEs) and medically attended events (MAEs) up to 12 months post-intervention. Secondary endpoints include the number of confirmed HSV-2 recurrent genital herpes (RGH) episodes and the HSV-2 shedding rate reduction. Participants will also be assessed for immunogenicity through antibody and T-cell response measurements at specified intervals.

Participant involvement may be terminated early if they fail to comply with study requirements, experience significant adverse events, or withdraw consent. The study aims to provide comprehensive data on the safety and efficacy of the HSV-targeted immunotherapy, contributing to the understanding and management of **Herpes Simplex** infections.

Treatment

The clinical trial involves the administration of several experimental medications, all formulated as **suspensions for injection**. These medications are developed by GlaxoSmithKline Biologicals S.A. and are administered via the **intramuscular route**. The active substances in these medications are identified by specific codes: GSKVX000000030810, GSKVX000000030918, and GSKVX000000030825. Each of these substances is categorized as either a "Structurally Diverse Substance - Vaccine" or "Specified Substance Group 1". The sponsor product codes for these experimental medications include GSKVx000000030778, GSKVx000000030776, GSKVx000000030767, GSKVx000000030784, GSKVx000000030770, GSKVx000000030782, GSKVx000000030774, GSKVx000000030772, and GSKVx000000030780. These medications are not formulated for pediatric use and are not classified as orphan drugs.

In addition to the experimental medications, a **placebo** is used in the study, identified as a NaCl solution. The NaCl solution does not have a specified pharmaceutical form or route of administration in the trial documentation. It serves as a comparator treatment to evaluate the efficacy and safety of the experimental medications. The placebo is not associated with any active substance or sponsor product code and is not intended for pediatric use.

Participant compliance with the dosing schedule is monitored throughout the trial, although specific details regarding the frequency and dosage of administration are not provided in the available data. The trial aims to assess the reactogenicity, safety, immune response, and efficacy of the HSV-targeted immunotherapy in participants, with a focus on reducing the risk of confirmed HSV-2 recurrent genital herpes episodes.

Efficacy

The efficacy of the HSV-targeted immunotherapy in the clinical trial will be assessed through several primary and secondary endpoints. The primary efficacy endpoint for Part II of the study is the **time-to-first confirmed HSV-2 recurrent genital herpes (RGH) episode**. This will be measured to determine the effectiveness of the immunotherapy in reducing the risk of confirmed HSV-2 RGH episodes. Secondary efficacy endpoints include the number of confirmed HSV-2 RGH episodes divided by the number of days of follow-up, the percentage of participants free from confirmed HSV-2 RGH episodes at six months after the last dose, and the HSV-2 shedding rate reduction from baseline to approximately six weeks post Dose 2 (Day 71).

Additional secondary endpoints involve the assessment of the number and duration of HSV-2 DNA shedding episodes during specified 28-day periods, as well as the geometric mean of gE-gI-specific CD4+/CD8+ T cells frequency expressing at least two activation markers. These markers include IFN-γ, TNF-α, IL-2, IL-13, IL-17, 4-1BB, and/or CD40L, and are assessed by CFC at various timepoints, including pre-study intervention administration (Day 1), post-Dose 1 (Day 29), and one month post-Dose 2 (Day 57). The study will also evaluate the anti-gE-gI antibody geometric mean concentration (GMC) and seropositivity rate, assessed by ELISA, at similar timepoints.

Inclusion and Exclusion 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 eDiary, return for follow-up visits).
"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. ria"
"5. Seronegative for 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 1 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 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 testing performed 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)."
"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)."

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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 or 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 (no laboratory testing required)."
"18. Hypersensitivity to latex."
"19. Recurrent history or uncontrolled neurological disorders or seizures."
"20. Haematological (haemoglobin level, white blood cell, platelet) and/or biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, blood urea nitrogen) 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/m2 or > 35 kg/m2."
"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 (including meningitis, encephalitis, radiculopathy, myelitis)."
"Prior/Concomitant Therapy 24. Use of any investigational or non-registered product (drug, vaccine, or medical device) 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 (e.g., infliximab)."
"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 (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, 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 (e.g., in case of pre-exposure prophylaxis to prevent HIV infection), 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."
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. "
"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."