Efficacy and Safety Study of SPL7013 Gel to Prevent the Recurrence of Bacterial Vaginosis (BV)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 3, Double-blind, Multicentre, Randomised, Placebo-controlled Study to Determine the Efficacy and Safety of SPL7013 Gel to Prevent the Recurrence of Bacterial Vaginosis

Conditions
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Bacterial Vaginosis

Intervention / Treatment
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* Drug: Metronidazole oral tablets 500mg
* Drug: 1% SPL7013 Gel
* Drug: Placebo gel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1% SPL7013 Gel<br>Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks | Drug: Metronidazole oral tablets 500mg<br>* One tablet taken orally twice daily for seven consecutive days<br>Drug: 1% SPL7013 Gel<br>* 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.<br>* Other names: astodimer sodium;|
| Placebo Comparator: Placebo Gel<br>Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks | Drug: Metronidazole oral tablets 500mg<br>* One tablet taken orally twice daily for seven consecutive days<br>Drug: Placebo gel<br>* 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | At or by the Week 16 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | At or by the Week 16 visit | 
| Recurrence of Patient-reported BV Symptoms | Number of participants with self-reported BV symptoms (vaginal discharge and/or odor) | At or by the Week 16 visit | 
| Recurrence of Individual Amsel Criteria | Number of participants with positive individual Amsel criterion - Clue cells representing at least 20% of total epithelial cells | At or by the Week 16 visit | 
| 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. | At or by the Week 16 visit | 
| 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) | At or by the Week 24 visit | 
| 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. | At or by the Week 16 visit | 
| 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. | Baseline to Week 16 | 
| Adverse Events (AEs) | Number of participants with genitourinary AEs considered potentially related to study treatment | From Baseline to end of Week 28 |