Bacterial Vaginosis
Conditions
Brief summary
A double-blind, phase 3 study to determine the efficacy of SPL7013 Gel when administered on alternate days for 16 weeks, compared to placebo gel in preventing the recurrence of BV in women with a history of recurrent BV.
Detailed description
Eligible participants, with both a history of recurrent BV and a current episode of BV, will receive a seven-day course of oral metronidazole. Participants who are successfully treated for their BV, and continue to be eligible, will be randomly assigned to receive either 1% SPL7013 Gel or placebo gel on alternate days at bed-time for 16 consecutive weeks. The primary endpoint will be determined at the conclusion of this 16 week treatment phase. Participants who experience a BV recurrence will be considered to have completed the study. Such participants will receive BV treatment in line with local practice and will not attend any further study visits. Participants who successfully reach Week 16 without a BV recurrence will enter a 12-week follow-up phase to Week 28. Participants will attend a study visit at 4-weekly intervals throughout the duration of the study to Week 28 (or up to the point of BV recurrence) to assess recurrence of BV and adverse events.
Interventions
One tablet taken orally twice daily for seven consecutive days
DRUG1% SPL7013 Gel
5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.
DRUGPlacebo gel
5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Sponsors
Starpharma Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Current active episode of BV (diagnosis defined as: At least 3 of the 4 Amsel criteria; Nugent score of at least 4; presence of BV-related symptoms) * History of recurrent BV (at least 3 episodes in previous year including current episode) * Using an effective method of contraception
Exclusion criteria
* Test positive for a sexually transmitted infection * Presence of genital Herpes Simplex Virus (HSV) lesions or Human Papilloma Virus (HPV) lesions requiring treatment * Abnormal pelvic exam, including presence of other vaginal or urinary tract infections * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | At or by the Week 16 visit | Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of Patient-reported BV Symptoms | At or by the Week 16 visit | Number of participants with self-reported BV symptoms (vaginal discharge and/or odor) |
| Recurrence of Individual Amsel Criteria | At or by the Week 16 visit | Number of participants with positive individual Amsel criterion \- Clue cells representing at least 20% of total epithelial cells |
| Recurrence of BV as Determined by Presence of a Nugent Score of 7-10 | At or by the Week 16 visit | Number of participants with a recurrence of BV as determined by presence of a Nugent score of 7-10 (BV), where 0-3 is normal, and 4-6 is intermediate. |
| Time to Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | At or by the Week 16 visit | Time to recurrence of BV (days), where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria) |
| Recurrence of BV According to the Composite Definition of at Least 3 Clinical Findings (Amsel Criteria) and a Nugent Score of 4-10. | At or by the Week 16 visit | Number of participants with a recurrence of BV according to the composite definition of at least 3 clinical findings (Amsel criteria) and a Nugent score of 4-10 (intermediate to BV), where 0-3 is normal. |
| Change From Baseline in Brief Index of Sexual Functioning for Women Questionnaire Composite Score | Baseline to Week 16 | Change from baseline in brief index of sexual functioning for women (BISF-W) questionnaire composite score. The composite score includes scores from dimensions (D) of thoughts/desire (D1, 0-12), arousal (D2, 0-12), frequency of sexual activity (D3, 0-12), receptivity/initiation (D4, 0-12), pleasure (D5, 0-12), relationship satisfaction (D6, 0-12), and any problems affecting sexual functioning (D7, 0-16). The composite score is calculated as D1+D2+D3+D4+D5+D6-D7 with a range of -16 to +75. A positive change in composite score from baseline to Week 16 reflects an improvement in sexual functioning, with a greater change in score indicating a greater improvement in sexual functioning. |
| Adverse Events (AEs) | From Baseline to end of Week 28 | Number of participants with genitourinary AEs considered potentially related to study treatment |
| Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | At or by the Week 24 visit | Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria) |
Countries
Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1% SPL7013 Gel Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks
Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days
1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks. | 294 |
| Placebo Gel Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks
Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days
Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks | 291 |
| Total | 585 |
Baseline characteristics
| Characteristic | 1% SPL7013 Gel | Placebo Gel | Total |
|---|---|---|---|
| Age, Continuous | 31.6 years STANDARD_DEVIATION 7.23 | 31.6 years STANDARD_DEVIATION 6.99 | 31.6 years STANDARD_DEVIATION 7.11 |
| Sex: Female, Male Female | 294 Participants | 291 Participants | 585 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 | — / — | — / — |
| other Total, other adverse events | 92 / 294 | 80 / 291 |
| serious Total, serious adverse events | 4 / 294 | 3 / 291 |
Outcome results
Primary
Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings
Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)
Time frame: At or by the Week 16 visit
Population: Analysis population is the modified intent-to-treat analysis population. One patient was excluded compared with the intent-to-treat population because they were dispensed medication but returned all unused.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | 130 Participants |
| Placebo Gel | Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | 158 Participants |
p-value: 0.015Regression, Logistic
Secondary
Adverse Events (AEs)
Number of participants with genitourinary AEs considered potentially related to study treatment
Time frame: From Baseline to end of Week 28
Population: Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Adverse Events (AEs) | 37 Participants |
| Placebo Gel | Adverse Events (AEs) | 33 Participants |
Secondary
Change From Baseline in Brief Index of Sexual Functioning for Women Questionnaire Composite Score
Change from baseline in brief index of sexual functioning for women (BISF-W) questionnaire composite score. The composite score includes scores from dimensions (D) of thoughts/desire (D1, 0-12), arousal (D2, 0-12), frequency of sexual activity (D3, 0-12), receptivity/initiation (D4, 0-12), pleasure (D5, 0-12), relationship satisfaction (D6, 0-12), and any problems affecting sexual functioning (D7, 0-16). The composite score is calculated as D1+D2+D3+D4+D5+D6-D7 with a range of -16 to +75. A positive change in composite score from baseline to Week 16 reflects an improvement in sexual functioning, with a greater change in score indicating a greater improvement in sexual functioning.
Time frame: Baseline to Week 16
Population: Analysis population includes only those participants who completed the survey, which was optional.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1% SPL7013 Gel | Change From Baseline in Brief Index of Sexual Functioning for Women Questionnaire Composite Score | 1.6 change in score on a scale |
| Placebo Gel | Change From Baseline in Brief Index of Sexual Functioning for Women Questionnaire Composite Score | 0.1 change in score on a scale |
Secondary
Recurrence of BV According to the Composite Definition of at Least 3 Clinical Findings (Amsel Criteria) and a Nugent Score of 4-10.
Number of participants with a recurrence of BV according to the composite definition of at least 3 clinical findings (Amsel criteria) and a Nugent score of 4-10 (intermediate to BV), where 0-3 is normal.
Time frame: At or by the Week 16 visit
Population: Modified Intent-to-Treat, excluding patients with missing values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Recurrence of BV According to the Composite Definition of at Least 3 Clinical Findings (Amsel Criteria) and a Nugent Score of 4-10. | 81 Participants |
| Placebo Gel | Recurrence of BV According to the Composite Definition of at Least 3 Clinical Findings (Amsel Criteria) and a Nugent Score of 4-10. | 111 Participants |
p-value: 0.008Regression, Logistic
Secondary
Recurrence of BV as Determined by Presence of a Nugent Score of 7-10
Number of participants with a recurrence of BV as determined by presence of a Nugent score of 7-10 (BV), where 0-3 is normal, and 4-6 is intermediate.
Time frame: At or by the Week 16 visit
Population: Modified Intent-to-Treat, excluding patients with missing values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Recurrence of BV as Determined by Presence of a Nugent Score of 7-10 | 95 Participants |
| Placebo Gel | Recurrence of BV as Determined by Presence of a Nugent Score of 7-10 | 135 Participants |
p-value: 0.012Regression, Logistic
Secondary
Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings
Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)
Time frame: At or by the Week 24 visit
Population: Analysis population is the modified intent-to-treat analysis population. One patient was excluded compared with the intent-to-treat population because they were dispensed medication but returned all unused.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | 194 Participants |
| Placebo Gel | Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | 213 Participants |
p-value: 0.059Regression, Logistic
Secondary
Recurrence of Individual Amsel Criteria
Number of participants with positive individual Amsel criterion \- Clue cells representing at least 20% of total epithelial cells
Time frame: At or by the Week 16 visit
Population: Modified Intent-to-Treat, excluding patients with missing values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Recurrence of Individual Amsel Criteria | 104 Participants |
| Placebo Gel | Recurrence of Individual Amsel Criteria | 132 Participants |
p-value: 0.014Regression, Logistic
Secondary
Recurrence of Patient-reported BV Symptoms
Number of participants with self-reported BV symptoms (vaginal discharge and/or odor)
Time frame: At or by the Week 16 visit
Population: Modified Intent-to-Treat, excluding patients with missing values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1% SPL7013 Gel | Recurrence of Patient-reported BV Symptoms | 75 Participants |
| Placebo Gel | Recurrence of Patient-reported BV Symptoms | 108 Participants |
p-value: 0.002Regression, Logistic
Secondary
Time to Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings
Time to recurrence of BV (days), where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)
Time frame: At or by the Week 16 visit
Population: Analysis population is the modified intent-to-treat analysis population. One patient was excluded compared with the intent-to-treat population because they were dispensed medication but returned all unused.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1% SPL7013 Gel | Time to Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | 105 days |
| Placebo Gel | Time to Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings | 99 days |
p-value: 0.007Log Rank