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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GlaxoSmithKline Biologicals

Participant type

Healthy volunteers, Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

6 Dec 2023 → 12 Jun 2025

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510571-37-00

EudraCT number

2021-003586-35

ClinicalTrials.gov

NCT05298254

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

"To evaluate the reactogenicity and safety of the HSVTI.
Only for PART II: To demonstrate the efficacy of the HSVTI in reducing the risk of having confirmed HSV-2 RGH episodes."

Secondary objectives 9

1. To evaluate the humoral immune response induced by the HSVTI
2. To evaluate the cellular immune response induced by the HSVTI
3. PART II: To compare the HSVTI to placebo in terms of incidence rate of RGH episodes
4. PART II: To compare the HSVTI to placebo in terms of percentage of RGH-free participants at 6 months after the last dose of study intervention
5. PART II: To compare the HSVTI to placebo in terms of severity of RGH episode associated symptoms during each RGH episode
6. PART II: To compare the HSVTI to placebo in terms of duration of RGH episode-associated symptoms, as assessed by the participant
7. PART II: To evaluate the lesion rate after administration of the last dose of the HSVTI
8. PART II (shedding sub-cohort): To evaluate the effect of the HSVTI, about 6 weeks after the last dose of the HSVTI on shedding rate
9. PART II (shedding sub-cohort): To evaluate the HSV shedding

Conditions and MedDRA coding

Herpes Simplex

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Federal Agency For Medicines And Health Products, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

IPD plan description

IPD plan description: GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents (e.g., Protocol, Statistical Analysis Plan, Clinical Study Report). Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to ‘Sharing Clinical Trial Data’ on the GSK Study Register (www.gsk-studyregister.com)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. 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. "2. Written informed consent obtained from the participant prior to performance of any study-specific procedure."
3. "3. Women of non-childbearing potential can be enrolled in the study. "
4. "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. "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. "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. "7. Only for PART I: Man or woman aged 18 to 40 years, included, at the time of the first study intervention administration."
8. "8. Only for PART I: Seronegative for HSV-2 as determined by Western blot performed at the Screening visit."
9. "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. "10. Only for PART II: Man or woman aged 18 to 60 years, included, at the time of the first study intervention administration."
11. "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)."
12. "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 23

1. "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. "
2. "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."
3. "16. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention."
4. "17. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)."
5. "18. Hypersensitivity to latex."
6. "19. Recurrent history or uncontrolled neurological disorders or seizures."
7. "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."
8. "21. Body mass index < 18 kg/m2 or > 35 kg/m2."
9. "22. Past or current Guillain-Barré syndrome."
10. "23. History of any form of ocular HSV infection, HSV-related erythema multiforme, or HSV-related neurological complications (including meningitis, encephalitis, radiculopathy, myelitis)."
11. "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. "
12. "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."
13. "26. Administration or planned administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab)."
14. "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."
15. "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."
16. "29. Prior receipt of another vaccine containing HSV antigens."
17. "30. Only for PART II: Planned use of suppressive anti-HSV therapy from the Screening visit until the end of the study."
18. "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."
19. "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."
20. 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).
21. "Prior/Concurrent Clinical Study Experience 34. Concurrently participating in another clinical study, at any time during the study period. "
22. "35. Pregnant or lactating women."
23. "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."

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. "• Percentage of participants reporting each solicited administration site event (redness, pain, and swelling) within 7 days (Day 1-Day 7) post-each dose. • Percentage of participants reporting each solicited systemic event (fever, fatigue, headache, myalgia, arthralgia) within 7 days (Day 1-Day 7) post-each dose. • Percentage of participants reporting unsolicited AEs within 28 days (Day 1-Day 28) post-each dose."
2. "• Percentage of participants reporting MAEs from Dose 1 (Day 1) up to 12 months after last study intervention administration (Day 394). • Percentage of participants reporting any SAEs from Dose 1 (Day 1) up to 12 months after last study intervention administration (Day 394). • Percentage of participants reporting any pIMDs (classified as newly diagnosed or exacerbation of pre-existing events) from Dose 1 (Day 1) up to 12 months after last study intervention administration (Day 394)."
3. "• Only for PART I: Percentage of participants reporting any haematological and biochemical laboratory abnormalities post Dose 1 (Day 8 and Day 29), post-Dose 2 (Day 36 and Day 64). • Only for PART II: Percentage of participants reporting any haematological and biochemical laboratory abnormalities post Dose 1 (Day 8 and Day 29), post Dose 2 (Day 36 and Day 57). "
4. "• Time-to-first confirmed HSV-2 RGH episode."

Secondary endpoints 5

1. •Number of confirmed HSV-2 RGH episodes divided by the number of days of follow-up assessed until end of RGH event reporting period •Percentage of participants free from confirmed HSV 2 RGH episode at 6months after the last dose of study intervention •HSC total score during each confirmed HSV-2 RGH episode assessed until end of RGH event reporting period •Number of days with RGH-associated symptoms during each confirmed HSV-2 RGH episode assessed until end of RGH event reporting period
2. • Number of days with confirmed HSV-2 genital herpes lesions divided by the number of days of follow-up assessed until end of RGH event reporting period. • HSV-2 shedding rate reduction (overall, asymptomatic and symptomatic) from baseline to about 6 weeks post Dose 2 (Day 71). • Number and duration of HSV-2 DNA shedding episodes during the 28-day periods starting at baseline (Day -28), Day 43, Day 181 (overall, asymptomatic and symptomatic).
3. • Only for PART I: Anti-gE-gI antibody GMC and seropositivity rate (assessed by ELISA) at pre study intervention administration (Day 1), post-Dose 1 (Day 29), post Dose 2 (Day 64), 6 months post Dose 2 (Day 209) and 12 months post-Dose 2 (Day 394). • Only for PART II: Anti-gE-gI antibody GMC and seropositivity rate (assessed by ELISA) at pre study intervention administration (Day 1), post-Dose 1 (Day 29), and 1 month post Dose 2 (Day 57).
4. • Only for PART I: Geometric mean of gE-gI-specific CD4+/CD8+ Tcells frequency expressing at least 2 activation markers (IFN-γ, TNF-α, IL-2, IL-13, IL17, 4-1BB and/or CD40L) and including at least one cytokine (assessed by CFC) at pre-study intervention administration (Day 1), postDose 1 (Day 29), postDose 2 (Day 64), 6 months postDose 2 (Day 209) and 12 months post-Dose 2 (Day 394).
5. • Only for PART II: Geometric mean of gE gI-specific CD4+/CD8+ T cells frequency expressing at least 2 activation markers (IFN-γ, TNF-α, IL-2, IL-13, IL 17, 4-1BB and/or CD40L) and including at least one cytokine (assessed by CFC) at pre-study intervention administration (Day 1), post Dose 1 (Day 29), and 1 month post-Dose 2 (Day 57).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 9

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GlaxoSmithKline Biologicals

Sponsor organisation

GlaxoSmithKline Biologicals

Address

Rue De L'Institut 89

City

Rixensart

Postcode

1330

Country

Belgium

Scientific contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

EU GSK Clinical Trials Call Center

Third parties 22

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 102 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications