Vaginitis Gardnerella
Conditions
Keywords
Amoxicillin, Gardnerella vaginalis, Vaginal Colonization
Brief summary
This is a randomized, double-blind, placebo-controlled Phase 2 study designed to determine if amoxicillin will eradicate vaginal colonization/infection with Gardnerella vaginalis (GV) when administered to women who are colonized/infected with GV but have no clinical evidence of Bacterial Vaginosis (BV). The study will be conducted at 2 clinics in the United States: University of Alabama at Birmingham and Wake Forest University Health Sciences. Entire study duration is approximately 24 months and subject participation duration is approximately 22 days. Approximately 245 healthy adult females, 18 to 45 years of age will be screened to enroll approximately 98 participants to achieve 82 evaluable participants at the test of cure (ToC) visit. Participants will be enrolled and randomized to one of two groups, either amoxicillin (2 x 250 mg capsules by mouth twice daily for 7 days) or placebo. Women who are enrolled will be asked to return for one further visit, Visit 2 (Day 15 - 21), where a ToC will be completed. For those not enrolled, participation will end at their post screening follow up phone call. Women will be asked to use condoms during their participation. The primary objective is to determine if treatment with amoxicillin eradicates GV in women who are colonized/infected with GV but have no clinical evidence of BV.
Detailed description
This is a randomized, double-blind, placebo-controlled Phase 2 study designed to determine if amoxicillin will eradicate vaginal colonization/infection with Gardnerella vaginalis (GV) when administered to women who are colonized/infected with GV but have no clinical evidence of Bacterial Vaginosis (BV). The study will be conducted at 2 clinics in the United States: University of Alabama at Birmingham and Wake Forest University Health Sciences. Entire study duration is approximately 24 months and subject participation duration is approximately 22 days. Approximately 245 healthy adult females, 18 to 45 years of age will be screened to enroll approximately 98 participants to achieve 82 evaluable participants at the test of cure (ToC) visit. Women who consent to screening participation will undergo pelvic examination on entry and vaginal specimens collected for pH, whiff test and wet prep microscopy (Amsel criteria with the exception of evaluation of vaginal discharge), Nugent score, nucleic acid amplification test (NAAT) for trichomonas, quantitative NAAT for GV, and microbiome analysis. At Visit 1 (Enrollment - Day 1), women who tested positive for GV by NAAT, negative for BV by Nugent, and negative for trichomonas by NAAT will be enrolled and randomized to one of two groups, either amoxicillin (2 x 250 mg capsules by mouth twice daily for 7 days) or placebo. Women who are enrolled will be asked to return for one further visit, Visit 2 (Day 15 - 21), where a ToC will be completed (a pelvic exam completed with the same specimens taken as those at baseline with the exception of the trichomonas NAAT). For those not enrolled, participation will end at their post screening follow up phone call. Women will be asked to use condoms during their participation. The primary objective is to determine if treatment with amoxicillin eradicates GV in women who are colonized/infected with GV but have no clinical evidence of BV. The secondary objective is to evaluate the safety and tolerability of amoxicillin compared to placebo.
Interventions
DRUGAmoxicillin
Amoxicillin is an aminopenicillin antibiotic
OTHERPlacebo
Placebo
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Women ages 18-45, inclusive. 2. No evidence of vaginitis (yeast, trichomonas, and BV/abnormal vaginal flora) or other vaginal conditions which in the opinion of the investigator could be confounders\*. \*These causes will initially be detected by wet mount microscopy with trichomonas during the screening procedures and later confirmed by NAAT and BV/abnormal vaginal flora confirmed by Nugent scoring (Nugent score of 4-10). 3. Presence of GV detected by NAAT\*. \*Results of NAAT testing will be available prior to return for Enrollment visit. 4. Willing to use condoms during vaginal intercourse while participating in the study. 5. Not currently menstruating at screening visit. 6. Willing and able to provide written informed consent. 7. Negative urine pregnancy test on all participants of childbearing potential at study screening. 8. Participant must be of non-childbearing potential\* or must be using highly effective birth control\*\* to avoid becoming pregnant. \*Non-childbearing potential is defined as being post-menopausal for at least 1 year, status after bilateral tubal ligation, or status after bilateral oophorectomy or status after hysterectomy. \*\*In addition to the required use of condoms by the male partner during study participation, participants must agree to avoid becoming pregnant by using one of the following acceptable method of birth control for 30 days prior to screening and for the duration of the study: * Intrauterine contraceptive device; OR * Oral contraceptives; OR * Hormonal injections; OR * Hormonal implants; OR * Contraceptive patches; OR * Monogamous relationship with vasectomized partner; OR * Exclusively same-sex relationships; OR * Abstinence 9. Participant is not planning on taking antibiotics or using any intravaginal microbicides from the Screening visit through the Visit 2 Follow-up (TOC). 10. Participant is willing and able to cooperate to the extent and degree required by this protocol at the discretion of the investigator.
Exclusion criteria
1. Pregnant or nursing. 2. Allergic to penicillin, amoxicillin, cephalosporins, or other ß-lactam antibiotic. 3. Use of antibiotics in the past 14 days prior to screening visit. 4. HIV infected. 5. Women taking immunosuppressive agents. 7\. History of renal impairment. 8. Use of any investigational drug within the past 30 days prior to screening. 9. Any other condition that, in the opinion of the investigator, would interfere with participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants With Eradication of Gardnerella Vaginalis (GV) in Each Study Arm at Visit 2 (Day 15-21) as Assessed by Nucleic Acid Amplification Test (NAAT). | Day 15 to 21 | Eradication of GV is defined by a negative NAAT result for GV at Visit 2. Participants who have a missing GV NAAT result at the test of cure (TOC) visit were classified as treatment failures. The denominator for proportions is based on the number of subjects who were randomized to the specified treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants Reporting Related Adverse Events (AEs and SAEs) in Each Study Arm Following the First Dose of Study Product Through Visit 2. | Day 1 through Day 15 to 21 | AEs were defined as any untoward medical occurrence in a participant administered a pharmaceutical product. SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. AEs and SAEs were collected from participants following the first dose of treatment through Visit 2 (Day 15-21). Events are included if deemed by the investigator to be related to the study product. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from women who were colonized/infected with Gardnerella vaginalis but have no clinical evidence of Bacterial Vaginosis. Enrollment occurred between 21SEP2017 and 08AUG2019.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received Amoxicillin placebo 2 capsules orally twice a day for 7 days, n=49
Placebo: Placebo | 49 |
| Amoxicillin Participants received Amoxicillin 2 x 250 mg capsules orally twice a day for 7 days, n=48
Amoxicillin: Amoxicillin is an aminopenicillin antibiotic | 48 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Amoxicillin |
|---|---|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 7.8 | 29.8 years STANDARD_DEVIATION 7.5 | 29.0 years STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 90 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 62 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 28 Participants | 13 Participants |
| Region of Enrollment United States | 49 participants | 97 participants | 48 participants |
| Sex: Female, Male Female | 49 Participants | 97 Participants | 48 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 45 |
| other Total, other adverse events | 3 / 47 | 10 / 45 |
| serious Total, serious adverse events | 0 / 47 | 0 / 45 |
Outcome results
Primary
The Proportion of Participants With Eradication of Gardnerella Vaginalis (GV) in Each Study Arm at Visit 2 (Day 15-21) as Assessed by Nucleic Acid Amplification Test (NAAT).
Eradication of GV is defined by a negative NAAT result for GV at Visit 2. Participants who have a missing GV NAAT result at the test of cure (TOC) visit were classified as treatment failures. The denominator for proportions is based on the number of subjects who were randomized to the specified treatment group.
Time frame: Day 15 to 21
Population: Participants included in the ITT population are those who randomized, regardless of whether they received study treatment or were compliant with the administration procedures or schedule.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Proportion of Participants With Eradication of Gardnerella Vaginalis (GV) in Each Study Arm at Visit 2 (Day 15-21) as Assessed by Nucleic Acid Amplification Test (NAAT). | 0.16 proportion of participants |
| Amoxicillin | The Proportion of Participants With Eradication of Gardnerella Vaginalis (GV) in Each Study Arm at Visit 2 (Day 15-21) as Assessed by Nucleic Acid Amplification Test (NAAT). | 0.21 proportion of participants |
p-value: 0.757Chi-squared, Corrected
Secondary
The Proportion of Participants Reporting Related Adverse Events (AEs and SAEs) in Each Study Arm Following the First Dose of Study Product Through Visit 2.
AEs were defined as any untoward medical occurrence in a participant administered a pharmaceutical product. SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. AEs and SAEs were collected from participants following the first dose of treatment through Visit 2 (Day 15-21). Events are included if deemed by the investigator to be related to the study product.
Time frame: Day 1 through Day 15 to 21
Population: Participants included in the safety population are those who randomized and received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Proportion of Participants Reporting Related Adverse Events (AEs and SAEs) in Each Study Arm Following the First Dose of Study Product Through Visit 2. | 0.04 proportion of participants |
| Amoxicillin | The Proportion of Participants Reporting Related Adverse Events (AEs and SAEs) in Each Study Arm Following the First Dose of Study Product Through Visit 2. | 0.18 proportion of participants |
p-value: 0.048Fisher Exact