Safety and Efficacy of GSK Neisseria Gonorrhoeae GMMA (NgG) Investigational Vaccine When Administered to Healthy Adults 18 to 50 Years of Age.

• ClinicalTrials.gov Identifier: NCT05630859
• Recruitment Status: Active, not recruiting
• First Posted: November 30, 2022
• Last Update Posted: April 22, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: November 25, 2022
• First Posted Date: November 30, 2022
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: November 28, 2022
• Estimated Primary Completion Date: May 23, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 25, 2022)

• Percentage of participants reporting solicited administration site events in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: During the 7 days follow-up period after the first dose ]
  The solicited administration site events after vaccination include pain, redness, and swelling.
• Percentage of participants reporting solicited administration site events in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: During the 7 days follow-up period after the second dose ]
  The solicited administration site events after vaccination include pain, redness, and swelling.
• Percentage of participants reporting each solicited systemic event in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: During the 7 days follow-up period after the first dose ]
  The solicited systemic events after vaccination include fever, headache, myalgia, arthralgia, fatigue. Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
• Percentage of participants reporting each solicited systemic event in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: During the 7 days follow-up period after the second dose ]
  The solicited systemic events after vaccination include fever, headache, myalgia, arthralgia, fatigue. Fever is defined as temperature ≥ 38.0°C/100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
• Percentage of participants reporting unsolicited adverse events (AEs) in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: During the 30 days follow-up period after the first dose ]
  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 will be reported as an unsolicited adverse event.
• Percentage of participants reporting unsolicited AEs in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: During the 30 days follow-up period after the second dose ]
  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 will be reported as an unsolicited adverse event.
• Percentage of participants reporting serious adverse events (SAEs) in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: From Day 1 after the first dose up to study Phase I end (Day 241) ]
  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 an abnormal pregnancy outcome.
• Percentage of participants reporting AEs leading to withdrawal in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: From Day 1 after the first dose up to study Phase I end (Day 241) ]
  An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. The AE may or may not be considered related to the study intervention.
• Percentage of participants with haematological and biochemical laboratory abnormalities in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: 7 days after the first dose ]
  Clinically significant 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 with haematological and biochemical laboratory abnormalities in study Phase 1 (Dose-escalation safety lead-in) [ Time Frame: 7 days after the second dose ]
  Clinically significant 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.
• Incidence rates of confirmed gonorrhea cases in study Phase 2 [Efficacy Proof of Concept (PoC)] [ Time Frame: From 1 month to 13 months post-Dose 2 ]
• Percentage of participants reporting solicited administration site events in study Phase 2 (Efficacy PoC) [ Time Frame: During the 7 days follow-up period after the first dose ]
  The solicited administration site events after vaccination include pain, redness, and swelling.
• Percentage of participants reporting solicited administration site events in study Phase 2 (Efficacy PoC) [ Time Frame: During the 7 days follow-up period after the second dose ]
  The solicited administration site events after vaccination include pain, redness, and swelling.
• Percentage of participants reporting each solicited systemic event in study Phase 2 (Efficacy PoC) [ Time Frame: During the 7 days follow-up period after the first dose ]
  The solicited systemic events after vaccination include fever, headache, myalgia, arthralgia, fatigue. Fever is defined as temperature ≥ 38.0°C/100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
• Percentage of participants reporting each solicited systemic event in study Phase 2 (Efficacy PoC) [ Time Frame: During the 7 days follow-up period after the second dose ]
  The solicited systemic events after vaccination include fever, headache, myalgia, arthralgia, fatigue. Fever is defined as temperature ≥ 38.0°C/100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
• Percentage of participants reporting unsolicited AEs in study Phase 2 (Efficacy PoC) [ Time Frame: During the 30 days follow-up period after the first dose ]
  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 will be reported as an unsolicited adverse event.
• Percentage of participants reporting unsolicited AEs in study Phase 2 (Efficacy PoC) [ Time Frame: During the 30 days follow-up period after the second dose ]
  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 will be reported as an unsolicited adverse event.
• Percentage of participants reporting SAEs in study Phase 2 (Efficacy PoC) [ Time Frame: From Day 1 after the first dose up to study end (Day 451) ]
  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 an abnormal pregnancy outcome.
• Percentage of participants reporting AEs leading to withdrawal in study Phase 2 (Efficacy PoC) [ Time Frame: From Day 1 after the first dose up to study end (Day 451) ]
  An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. The AE may or may not be considered related to the study intervention.
• Percentage of participants with haematological and biochemical laboratory abnormalities in study Phase 2 (Efficacy PoC) [ Time Frame: 7 days after the first dose ]
  Clinically significant 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 participants condition. The evaluation of the endpoint will be assessed in the subsets for intensive safety monitoring.
• Percentage of participants with haematological and biochemical laboratory abnormalities in study Phase 2 (Efficacy PoC) [ Time Frame: 7 days after the second dose ]
  Clinically significant 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 4, 2023)

• Incidence rates of confirmed gonorrhea cases with and without co-infection with a different sexually-transmitted disease causing bacterium in study Phase 2 (Efficacy PoC) [ Time Frame: From 1 month to 13 months post-Dose 2 ]
• Incidence rates of gonorrhea in study Phase 2 (Efficacy PoC) [ Time Frame: From 1 month to 13 months post-Dose 2 ]
• Incidence rates of other gonococcal infection with positive Ng in study Phase 2 (Efficacy PoC) [ Time Frame: From 1 month to 13 months post-Dose 2 ]

Original Secondary Outcome Measures (submitted: November 25, 2022)

• Incidence rates of confirmed gonorrhea cases with and without co-infection with a different sexually-transmitted disease causing bacterium in study Phase 2 (Efficacy PoC) [ Time Frame: From 1 month to 13 months post-Dose 2 ]
• Incidence rates of gonorrhea in study Phase 2 (Efficacy PoC) [ Time Frame: From 1 month to 13 months post-Dose 2 ]
• Incidence rates of other gonococcal infection with positive NG in study Phase 2 (Efficacy PoC) [ Time Frame: From 1 month to 13 months post-Dose 2 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of GSK Neisseria Gonorrhoeae GMMA (NgG) Investigational Vaccine When Administered to Healthy Adults 18 to 50 Years of Age.
• Official Title: A Phase 1/2, Observer-blind, Randomized, Placebo-controlled Multi-country Study to Assess Safety and Efficacy of GSK Neisseria Gonorrhoeae GMMA (NgG) Investigational Vaccine When Administered to Healthy Adults 18 to 50 Years of Age
• Brief Summary: The aim of this first time in human proof of concept (FTiH-PoC) study is to evaluate safety and reactogenicity, to demonstrate efficacy and to explore immunogenicity of GlaxoSmithKline's (GSK) Neisseria gonorrhoeae generalized modules for membrane antigens (GMMA) (NgG) investigational vaccine compared to placebo (saline).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Data will be collected in an observer-blind manner.

Primary Purpose: Prevention

• Condition: Sexually Transmitted Diseases

Intervention

• Biological: NgG low dose investigational vaccine
  Two doses of NgG low dose investigational vaccine, administered intramuscularly.
• Biological: NgG medium dose investigational vaccine
  Two doses of NgG medium dose investigational vaccine, administered intramuscularly.
• Biological: NgG high dose investigational vaccine
  Two doses of NgG high dose investigational vaccine, administered intramuscularly.
• Biological: Placebo
  Two doses of placebo, administered intramuscularly.
  Other Name: Sodium chloride (NaCl)
• Biological: NgG HTD investigational vaccine
  Two doses of NgG HTD investigational vaccine, administered intramuscularly.
• Biological: NgG below HTD investigational vaccine
  Two doses of NgG below HTD investigational vaccine, administered intramuscularly.

Study Arms

• Experimental: Phase 1:1a Low dose Group
  Participants randomized to the 1a Low dose Group receive 2 doses of NgG low dose investigational vaccine.
  Intervention: Biological: NgG low dose investigational vaccine
• Placebo Comparator: Phase 1:1b Placebo Group
  Participants randomized to the 1b Placebo Group receive 2 doses of placebo.
  Intervention: Biological: Placebo
• Experimental: Phase 1: 2a Medium dose Group
  Participants randomized to the 2a Medium dose Group receive 2 doses of NgG medium dose investigational vaccine.
  Intervention: Biological: NgG medium dose investigational vaccine
• Placebo Comparator: Phase 1: 2b Placebo Group
  Participants randomized to the 2b Placebo Group receive 2 doses of placebo.
  Intervention: Biological: Placebo
• Experimental: Phase 1: 3a High dose Group
  Participants randomized to the 3a High dose Group receive 2 doses of NgG high dose investigational vaccine.
  Intervention: Biological: NgG high dose investigational vaccine
• Placebo Comparator: Phase 1: 3b Placebo Group
  Participants randomized to the 3b Placebo Group receive 2 doses of placebo.
  Intervention: Biological: Placebo
• Experimental: Phase 2: 4a HTD Group
  Participants randomized to the 4a highest tolerated dose (HTD) Group receive 2 doses of NgG highest tolerated dose selected from Phase 1.
  Intervention: Biological: NgG HTD investigational vaccine
• Experimental: Phase 2: 4b dose below HTD Group
  Participants randomized to the 4b dose below HTD Group receive 2 doses of NgG dose below the highest tolerated dose selected from Phase 1.
  Intervention: Biological: NgG below HTD investigational vaccine
• Placebo Comparator: Phase 2: 4c Placebo Group
  Participants randomized to the 4c Placebo Group receive 2 doses of placebo.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 19, 2024): 1004
• Original Estimated Enrollment (submitted: November 25, 2022): 774
• Estimated Study Completion Date: May 23, 2025
• Estimated Primary Completion Date: May 23, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Inclusion criteria for the dose-escalation safety lead-in part

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
• Healthy participants as established by medical history, clinical examination, and laboratory assessment.
• A participant between and including 18 and 50 years of age at the time of informed consent.
• Female participants of non-childbearing potential may be enrolled in the study.

• Female participants of childbearing potential may be enrolled in the study if the participant:

  • has practiced adequate contraception for 1 month prior to study intervention administration, and
  • has a negative pregnancy test on the day of study intervention administration, and
  • has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.

Inclusion criteria for the efficacy PoC part

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.

• Healthy participants as established by:

  • For the 2 intensive safety monitoring subsets (i.e., first 30 HIV negative subjects per group followed by first 8 HIV positive subjects per group): medical history, clinical examination, and laboratory assessment.
  • For all the remaining participants: medical history, clinical examination.
• At risk for gonococcus infections based on sexual behavioral characteristics: this may include men having sex with men, pre-exposure prophylaxis for HIV users, individuals who engage in transactional sex participants with current or past STI diagnosis, participants at time of STI screening or seeking other STI services.
• A participant between and including 18 and 50 years of age at the time of informed consent. Transgender men and women, and other gender non-conforming people who identify themselves as neither men nor women may be enrolled into the study, based on their risk factors. For the purpose of this study, they will be followed up according to their biological sex (sex at birth), sexual orientation, and genital/sexual anatomy
• Participants of non-childbearing potential may be enrolled in the study. This includes transmen that have not undergone gender affirming surgery of their genitals.

• Participants of childbearing potential may be enrolled in the study if the participant:

  • has practiced adequate contraception for 1 month prior to study intervention administration, and
  • has a negative pregnancy test on the day of study intervention administration, and
  • has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.

Exclusion criteria:

1. Medical conditions Dose-escalation safety lead-in part

   • Any clinically significant biochemical laboratory abnormality.
   • Any other clinical condition as determined by the investigator, that may increase participant's risk due to study participation.
   • History of any reaction/hypersensitivity likely to be exacerbated by any component of the study intervention.
   • Confirmed or suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination.
   • Hypersensitivity to latex.
   • Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality, as determined by physical examination/laboratory tests.
   • Uncontrolled neurological disorders or seizures.
   • History of invasive meningococcal disease. Efficacy PoC part: HIV negative intensive safety monitoring, HIV negative full enrollment and for all remaining participants
   • Persons under guardianship or trusteeship.
   • Persons deprived of liberty.
   • Gonococcal infection identified within 14 days prior to randomization.
   • Any other clinical condition as determined by the investigator, that may increase participant's risk due to study participation.
   • History of severe allergic reactions and/anaphylaxis, or any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
   • Bleeding diathesis / any other condition that would contraindicate intramuscular administration.
   • Confirmed or suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination.
   • Known seropositivity for HIV infection, regardless of viremia and CD4 cell count
   • Hypersensitivity to latex.
   • Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality, as determined by physical examination/laboratory tests.
   • Recurrent history/uncontrolled neurological disorders or seizures.
   • History of invasive meningococcal disease.

   The exclusion criteria depicted above, and the following exclusions criterion applies only for the HIV positive participants (intensive safety monitoring subset and full enrollment of HIV positive participants):

   Seropositivity for HIV infection if:

   • CD4 cell count < 350 cells/mm3 in the last 6 months
   • viral load > 50cp/ml in the last 6 months
   • participant is not on antiretroviral therapy (ART) for > 3 months or has switched from a different ART in the last 3 months.

   For both Intensive safety monitoring subset (first 30 HIV negative subjects per group and first 8 HIV positive subjects per group) these criteria apply:

   Any clinically significant hematological/biochemical laboratory abnormality.

2. Prior/Concomitant therapy Applicable for both the dose-escalation safety lead-in part and the PoC part

   • Use of any investigational/non-registered product other than the study intervention(s) within 30 days before the first dose/planned use during the study period.
   • Previous and planned vaccination with an OMV based Neisseria meningitidis group B vaccine (e.g., Bexsero, MeNZB vaccine or MenBvac at any time prior to first dose and during the entire study period.
   • Planned administration/administration of a vaccine not specified in study protocol within 15 days before the first dose and ending 15 days after the last dose of vaccine administration.
   • Administration of long-acting immune-modifying drugs during the period starting 6 months prior to the first dose of study intervention/planned administration at any time during the study period.
   • Administration of immunoglobulins /any blood products/plasma derivatives during the period starting 3 months before the administration of the first dose of study intervention/planned administration during the study period.
   • Chronic administration (more than 14 days in total) of immunosuppressants/other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day. Inhaled and topical steroids are allowed.

   The following criterion applies only for the PoC part:

   •Chronic/long-term use of systemic antibiotics with an activity against Neisseria gonorrhoeae.

3. Prior/Concurrent clinical study experience applicable for both dose-escalation safety lead-in part and the PoC part Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational/a non-investigational intervention.

4. Other exclusions applicable for both dose-escalation safety leading part and the PoC part

   • Pregnant/lactating female.
   • Female planning to become pregnant/to discontinue contraceptive precautions before 1 month after completion of the study intervention administration series.
   • Any study personnel/their immediate dependents, family/household members.
   • Lifestyle consideration that may interfere with the conduct of the study/pose additional risks to the rights and wellbeing of participants.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, France, Germany, Philippines, South Africa, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05630859
• Other Study ID Numbers: 216156; 2022-500883-37-00 ( Other Identifier: EU CT number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: GlaxoSmithKline
• Verification Date: April 2024