Sexually Transmitted Diseases
Conditions
Keywords
Neisseria gonorrhoeae, Safety, Efficacy, Sexually transmitted infection, Healthy adults 18 to 50 years of age
Brief summary
The aim of this first time in human proof of concept (FTiH-PoC) study was 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
The study included the following parts: * Phase 1 - Dose-escalation safety lead-in in healthy participants. * Phase 2 - Efficacy PoC in healthy participants considered at risk for gonorrhea. The doses to be tested for efficacy would be selected based on the safety evaluation performed during the dose-escalation safety lead-in: in case more than one dose would show tolerability, the highest tolerated dose (HTD) and the dose below the highest tolerated (i.e., 2 doses) would be advanced in the efficacy PoC part of the study and compared versus placebo. In case only the lowest dose shows adequate tolerability, this would be the only dose tested in the PoC versus placebo.
Interventions
BIOLOGICALNgG 12.5 µg investigational vaccine
2 doses of NgG 12.5 µg investigational vaccine administered intramuscularly.
BIOLOGICALNgG 25 µg investigational vaccine
2 doses of NgG 25 µg investigational vaccine administered intramuscularly.
BIOLOGICALNgG 50 µg investigational vaccine
2 doses of NgG 50 µg investigational vaccine administered intramuscularly.
COMBINATION_PRODUCTPlacebo
2 doses of placebo administered intramuscularly.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data was collected in an observer-blind manner.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants Reporting Any Solicited Administration Site Events | From Day 1 to Day 7 | Assessed solicited administration site events included injection site pain, erythema (redness), and swelling. Any = occurrence of the event regardless of intensity grade. |
| Phase 1: Number of Participants Reporting Any Solicited Systemic Events | From Day 1 to Day 7 | Assessed solicited systemic events included headache, fatigue (tiredness), myalgia (muscle pain), arthralgia (joint pain), and fever (pyrexia). Fever is defined as body temperature \>=38ºC; preferred location for measuring the temperature is oral cavity. Any = occurrence of the event regardless of intensity grade. |
| Phase 1: Number of Participants Reporting Any Unsolicited Adverse Events (AEs) | From Day 1 to Day 30 | An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade. |
| Phase 1: Number of Participants Reporting Any Unsolicited AEs | From Day 61 to Day 90 | An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade. |
| Phase 1: Number of Participants Reporting Any Serious Adverse Events (SAEs) and AEs Leading to Withdrawal | From Day 1 after the first dose to Day 241 | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcome or any other situation as determined by the investigator. 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. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for them since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade. |
| Phase 1: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values | At Day 8 compared to baseline (Day 1) | The safety laboratory data included haematological parameters \[hemoglobin, lymphocytes, platelets, neutrophils, and white blood cells (WBC)\] and biochemical parameters (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\], Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 1 (baseline) and Day 8 haematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. |
| Phase 2: Incidence Rate of Confirmed Gonorrhea Cases | From 1 month post-Dose 2 (Day 91) to 13 months post-Dose 2 (Day 451) | Incidence of first confirmed gonorrhea cases by positive Nucleic Acid Amplification Test (NAAT) at the anorectal and/or urogenital location were evaluated. The incidence rate (y/PT) of confirmed gonorrhea cases, expressed in terms of 100 person-years, was calculated as the number of confirmed gonorrhea cases (y) in a group, over the sum of individual person-times at risk (PT) in the same group, and multiplied by 100. |
| Phase 2: Number of Participants Reporting Any Solicited Administration Site Events | From Day 1 to Day 7 | Assessed solicited administration site events included injection site pain, erythema (redness), and swelling. Any = occurrence of the event regardless of intensity grade. |
| Phase 2: Number of Participants Reporting Any Solicited Systemic Events | From Day 1 to Day 7 | Assessed solicited systemic events included headache, fatigue (tiredness), myalgia (muscle pain), arthralgia (joint pain), and fever (pyrexia). Fever is defined as body temperature \>=38ºC; preferred location for measuring the temperature is oral cavity. Any = occurrence of the event regardless of intensity grade. |
| Phase 2: Number of Participants Reporting Any Unsolicited AEs | From Day 1 to Day 30 | An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade. |
| Phase 2: Number of Participants Reporting Any SAEs and AEs Leading to Withdrawal | From Day 1 after the first dose to Day 451 | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcome or any other situation as determined by the investigator. 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. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for them since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade. |
| Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values in HIV Negative (HIV-) Subset | At Day 8 compared to baseline (Day 1) | The safety laboratory data included haematological parameters (hemoglobin, lymphocytes, platelets, neutrophils, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 1 (baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. |
| Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values for HIV Positive (HIV+) Subset | At Day 8 compared to baseline (Day 1) | The safety laboratory data included haematological parameters (hemoglobin, absolute lymphocyte count, platelets, absolute neutrophil count, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 1 (baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint. |
| Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values for HIV- Subset | At Day 68 compared to baseline (Day 61) | The safety laboratory data included haematological parameters (hemoglobin, lymphocytes, platelets, neutrophils, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 61 (baseline) and Day 68 haematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint. |
| Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values HIV+ Subset | At Day 68 compared to baseline (Day 61) | The safety laboratory data included haematological parameters (hemoglobin, absolute lymphocyte count, platelets, absolute neutrophil count, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 61 (baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Incidence Rates of Confirmed Gonorrhea Cases With and Without Chlamydia Trachomatis Co-infection | From 1 month post-Dose 2 (Day 91) to 13 months post-Dose 2 (Day 451) | Confirmed gonorrhea cases by positive NAAT with and without chlamydia trachomatis co-infection at the pharyngeal and/or anorectal and/or urogenital location are reported. The incidence rate (y/PT) of confirmed gonorrhea cases with and without Chlamydia Trachomatis co-infection, expressed in terms of 100 person-years, was calculated as the number of confirmed gonorrhea cases with and without Chlamydia Trachomatis co-infection (y) in a group, over the sum of individual person-times at risk (PT) in the same group, and multiplied by 100. |
| Phase 2: Incidence Rates of Symptomatic and Confirmed Gonorrhea Cases | From 1 month post-Dose 2 (Day 91) to 13 months post-Dose 2 (Day 451) | Symptomatic gonorrhea cases which were later confirmed gonorrhea cases are reported. Symptomatic gonorrhea cases are defined as participants with symptoms suggestive of gonorrhea at the infected anatomical site which were later confirmed by a positive NAAT at the anorectal and/or urogenital location. The incidence rate (y/PT) of confirmed gonorrhea cases, expressed in terms of 100 person-years, was calculated as the number of confirmed gonorrhea cases (y) in a group, over the sum of individual person-times at risk (PT) in the same group, and multiplied by 100. |
Countries
Brazil, France, Germany, Philippines, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 1009 participants were included in the enrolled set, out of which only 1004 were included in the exposed set and started the study. The study was conducted in 2 phases: Phase 1 was the Dose-escalation safety lead-in (SLI) phase and Phase 2 was the Efficacy Proof of Concept (PoC) phase.
Pre-assignment details
Phase 1 Placebo group: Enrollment in the Phase 1 portion of the study proceeded stepwise to allow three increasing dosages of the candidate vaccine to be tested against placebo. In this record we present the pooled Phase 1 placebo analysis group, which includes all participants who received placebo during Phase 1.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.9 YEARS STANDARD_DEVIATION 7.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 222 Participants |
| Race/Ethnicity, Customized Multiple | 4 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 329 | 0 / 327 | 0 / 324 |
| other Total, other adverse events | 5 / 6 | 4 / 6 | 6 / 6 | 5 / 6 | 303 / 329 | 305 / 327 | 232 / 324 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 3 / 329 | 11 / 327 | 3 / 324 |
Outcome results
None listed