Clinical trial NCT05298254: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Herpes Simplex
Keywords: First Time in Human
Healthy participants
Recurrent genital herpes
Herpes Simplex Virus
Reactogenicity
Safety
Immune response
Efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-03-28
Enrollment: 505
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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.

Primary outcomes:
measure: Percentage of participants reporting each solicited administration site event
timeFrame: Within 7 days after the first study intervention dose (administered at Day 1)
measure: Percentage of participants reporting each solicited administration site event
timeFrame: Within 7 days after the second study intervention dose (administered at Day 29)
measure: Percentage of participants reporting each solicited systemic event
timeFrame: Within 7 days after the first study intervention dose (administered at Day 1)
measure: Percentage of participants reporting each solicited systemic event
timeFrame: Within 7 days after the second study intervention dose (administered at Day 29)
measure: Percentage of participants reporting unsolicited adverse events (AEs)
timeFrame: Within 28 days after the first study intervention dose (administered at Day 1)
measure: Percentage of participants reporting unsolicited adverse events (AEs)
timeFrame: Within 28 days after the second study intervention dose (administered at Day 29)
measure: Percentage of participants reporting medically attended events (MAEs)
timeFrame: From Dose 1 (Day 1) up 12 months after last study intervention administration (Day 394)
measure: 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)
measure: 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)
measure: 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)
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part I of the study
timeFrame: At Day 8
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in Part I of the study
timeFrame: At Day 29
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part I of the study
timeFrame: At Day 36
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 64 in Part I of the study
timeFrame: At Day 64
measure: 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)
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part II of the study
timeFrame: At Day 8
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in part II of the study
timeFrame: At Day 29
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part II of the study
timeFrame: At Day 36
measure: Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 57 in Part II of the study
timeFrame: At Day 57
measure: 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
Secondary outcomes:
measure: 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
measure: 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)
measure: 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
measure: 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
measure: 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
measure: 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)
measure: Number of HSV-2 DNA shedding episodes in Part II of the study
timeFrame: Day -28 to Day -1
measure: Number of HSV-2 DNA shedding episodes in Part II of the study
timeFrame: Day 43 to Day 70
measure: Number of HSV-2 DNA shedding episodes in Part II of the study
timeFrame: Day 181 to Day 208
measure: Duration of HSV-2 DNA shedding episodes in Part II of the study
timeFrame: Day -28 to Day -1
measure: Duration of HSV-2 DNA shedding episodes in Part II of the study
timeFrame: Day 43 to Day 70
measure: Duration of HSV-2 DNA shedding episodes in Part II of the study
timeFrame: Day 181 to Day 208
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Bochum
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Marbella
country: Spain
facility: GSK Investigational Site
city: Brighton
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: