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
Overview
- Phase
- Phase 1
- Intervention
- Non-adjuvanted HSV formulation 1
- Conditions
- Herpes Simplex
- Sponsor
- GlaxoSmithKline
- Enrollment
- 505
- Locations
- 1
- Primary Endpoint
- Percentage of participants reporting each solicited administration site event
- Status
- Completed
- Last Updated
- 7 months ago
Overview
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.
Investigators
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.
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\^
- •Past or current Guillain-Barré syndrome.
Arms & Interventions
Non-adjuvanted HSV formulation 1 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the non-adjuvanted HSV formulation 1 vaccine, one at Day 1 and one at Day 29.
Intervention: Non-adjuvanted HSV formulation 1
Non-adjuvanted HSV formulation 2 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the non-adjuvanted HSV formulation 2 vaccine, one at Day 1 and one at Day 29.
Intervention: Non-adjuvanted HSV formulation 2
Non-adjuvanted HSV formulation 3 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the non-adjuvanted HSV formulation 3 vaccine, one at Day 1 and one at Day 29.
Intervention: Non-adjuvanted HSV formulation 3
HSV formulation 1 with adjuvant 1 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 1 with adjuvant 1 vaccine, one at Day 1 and one at Day 29.
Intervention: HSV formulation 1 with adjuvant 1
HSV formulation 2 with adjuvant 1 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 2 with adjuvant 1 vaccine, one at Day 1 and one at Day 29.
Intervention: HSV formulation 2 with adjuvant 1
HSV formulation 3 with adjuvant 1 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 3 with adjuvant 1 vaccine, one at Day 1 and one at Day 29.
Intervention: HSV formulation 3 with adjuvant 1
HSV formulation 1 with adjuvant 2 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 1 with adjuvant 2 vaccine, one at Day 1 and one at Day 29.
Intervention: HSV formulation 1 with adjuvant 2
HSV formulation 2 with adjuvant 2 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 2 with adjuvant 2 vaccine, one at Day 1 and one at Day 29.
Intervention: HSV formulation 2 with adjuvant 2
HSV formulation 3 with adjuvant 2 - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of the HSV formulation 3 with adjuvant 2 vaccine, one at Day 1 and one at Day 29.
Intervention: HSV formulation 3 with adjuvant 2
Placebo - Part I Group
Participants enrolled in Part I of the study who receive 2 doses of Placebo, one at Day 1 and one at Day 29.
Intervention: Placebo
HSVTI formulation (F) 1 - Part II Group
Participants enrolled in Part II of the study who receive 2 doses of the formulation of the HSVTI\_F1 selected from Part I of the study, one at Day 1 and one at Day 29.
Intervention: HSVTI_F1
HSVTI_F2 - Part II Group
Participants enrolled in Part II of the study who receive 2 doses of the HSVTI\_F2 selected from Part I of the study, one at Day 1 and one at Day 29.
Intervention: HSVTI_F2
Placebo - Part II Group
Participants enrolled in Part II of the study who receive 2 doses of Placebo, one at Day 1 and one at Day 29.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of participants reporting each solicited administration site event
Time Frame: Within 7 days after the second study intervention dose (administered at Day 29)
The solicited administration site events are pain, redness and swelling.
Percentage of participants reporting each solicited systemic event
Time Frame: 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.
Percentage of participants reporting unsolicited adverse events (AEs)
Time Frame: 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.
Percentage of participants reporting medically attended events (MAEs)
Time Frame: 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.
Percentage of participants reporting any serious adverse events (SAEs)
Time Frame: 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.
Percentage of participants reporting any potential immune-mediated disease (pIMDs) (classified as newly diagnosed or exacerbation of pre-existing events)
Time Frame: 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.
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at pre-study intervention administration (Day 1) in Part I of the study
Time Frame: 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.
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part I of the study
Time Frame: At Day 8
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in Part I of the study
Time Frame: At Day 29
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part I of the study
Time Frame: At Day 36
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 64 in Part I of the study
Time Frame: At Day 64
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at pre-study intervention administration (Day 1) in Part II of the study
Time Frame: At pre-study intervention administration (Day 1)
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 8 in Part II of the study
Time Frame: At Day 8
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 29 in part II of the study
Time Frame: At Day 29
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 36 in Part II of the study
Time Frame: At Day 36
Percentage of participants reporting any haematological and biochemical laboratory abnormalities at Day 57 in Part II of the study
Time Frame: At Day 57
Time-to-first confirmed HSV-2 RGH episode in Part II of the study
Time Frame: 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.
Secondary Outcomes
- Number of confirmed HSV-2 RGH episodes in Part II of the study(14 days post-Dose 2 (Day 43) to end of RGH event reporting period)
- Percentage of participants free from confirmed HSV-2 RGH episode in Part II of the study(At 6 months after the last study intervention administration (Day 29))
- Herpes Symptoms Checklist (HSC) total score during each confirmed HSV-2 RGH episode in Part II of the study(14 days post-Dose 2 (Day 43) to end of RGH event reporting period)
- Number of days with RGH-associated symptoms during each confirmed HSV-2 RGH episode in Part II of the study(14 days post-Dose 2 (Day 43) to end of RGH event reporting period)
- Number of days with confirmed HSV-2 genital herpes lesions in Part II of the study(14 days post-Dose 2 (Day 43) to end of RGH event reporting period)
- HSV-2 shedding rate reduction from baseline to 6 weeks post-Dose 2 (Day 71) in Part II of the study(At 6 weeks post-Dose 2 (Day 71) compared to baseline (Day -28 to Day -1))
- Number of HSV-2 DNA shedding episodes in Part II of the study(Day 181 to Day 208)
- Duration of HSV-2 DNA shedding episodes in Part II of the study(Day 181 to Day 208)
- 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)
- Anti-HSVTI antibody geometric mean concentrations (GMCs) in Part II of the study(At pre-study intervention administration (Day 1), Day 29 and Day 57)
- 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)
- Percentage of seropositive participants for anti-HSVTI antibodies in Part II of the study(At pre-study intervention administration (Day 1), Day 29 and Day 57)
- 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)
- 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 and Day 57)
- 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)
- 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 and Day 57)