Clinical Trial Results:
A phase 3, double-blind, multicentre, randomised, placebo-controlled study to determine the efficacy and safety of SPL7013 Gel (VivaGel®) to prevent the recurrence of bacterial vaginosis
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Summary
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EudraCT number |
2014-000694-39 |
Trial protocol |
CZ GB HU BG |
Global end of trial date |
04 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Aug 2021
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First version publication date |
07 Aug 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SPL7013-018
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02236156 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Starpharma Pty Ltd
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Sponsor organisation address |
4-6 Southampton Crescent, Abbotsford, Australia, 3067
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Public contact |
VP Development and Regulatory Affairs, Starpharma Pty Ltd, jeremy.paull@starpharma.com
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Scientific contact |
VP Development and Regulatory Affairs, Starpharma Pty Ltd, jeremy.paull@starpharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Aug 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jul 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Oct 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine the efficacy of 1% SPL7013 Gel in reducing recurrent bacterial vaginosis (BV) in women with a history of recurrent BV.
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Protection of trial subjects |
The study was conducted in accordance with Good Clinical Practice (GCP) as required by the International Council for Harmonisation guidelines and in accordance with country-specific laws and regulations governing clinical studies of investigational products (IPs). Compliance with these requirements also constitutes conformity with the ethical principles of the Declaration of Helsinki. An informed consent document approved by each study centre’s IRB/IEC was signed by the subject or legal representative and the investigator before any study-related procedures were performed. The investigator provided copies of the signed informed consent to the subject or legal representative, and the original was retained by the investigator.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Romania: 119
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Country: Number of subjects enrolled |
United Kingdom: 22
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Country: Number of subjects enrolled |
Bulgaria: 145
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Country: Number of subjects enrolled |
Czechia: 60
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Country: Number of subjects enrolled |
Hungary: 130
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Country: Number of subjects enrolled |
Ukraine: 113
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Country: Number of subjects enrolled |
Thailand: 6
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Country: Number of subjects enrolled |
United States: 42
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Worldwide total number of subjects |
637
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EEA total number of subjects |
454
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
637
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects aged 18-45 years with current BV (3/4 Amsel criteria, Nugent score 4-10 and symptoms of vaginal discharge and/or unpleasant vaginal odour), and history of recurrent BV (3 episodes in last 12 months, including current), and after metronidazole therapy, BV had to be resolved (no symptoms and negative for discharge, whiff test, clue cells) | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Double-blind treatment phase (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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SPL7013 Gel | ||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
1% SPL7013 Gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Vaginal use
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Dosage and administration details |
5 g every second day for 16 weeks
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Arm title
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Placebo Gel | ||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo Gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Vaginal use
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Dosage and administration details |
5 g every second day for 16 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Double-blind treatment phase
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SPL7013 Gel
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Reporting group description |
- | ||
Reporting group title |
Placebo Gel
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Reporting group description |
- | ||
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End point title |
Recurrence of BV | |||||||||
End point description |
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)
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End point type |
Primary
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End point timeframe |
At or by the Week 16 visit
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Statistical analysis title |
Recurrence of BV at or by Week 16 | |||||||||
Comparison groups |
SPL7013 Gel v Placebo Gel
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Number of subjects included in analysis |
636
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.027 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.64
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.43 | |||||||||
upper limit |
0.95 | |||||||||
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End point title |
Time to recurrence of BV | ||||||||||||
End point description |
Time to recurrence of BV (days), where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)
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End point type |
Secondary
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End point timeframe |
At or by the Week 16 visit
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Statistical analysis title |
Time to recurrence | ||||||||||||
Comparison groups |
Placebo Gel v SPL7013 Gel
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Number of subjects included in analysis |
636
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.009 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.56
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.4 | ||||||||||||
upper limit |
0.9 | ||||||||||||
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End point title |
Recurrence of patient-reported BV symptoms | |||||||||
End point description |
Number of participants with self-reported BV symptoms (vaginal discharge and/or odor)
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End point type |
Secondary
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End point timeframe |
At or by the Week 16 visit
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Statistical analysis title |
Recurrence of BV Symptoms | |||||||||
Comparison groups |
SPL7013 Gel v Placebo Gel
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Number of subjects included in analysis |
621
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.012 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.59
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.39 | |||||||||
upper limit |
0.89 | |||||||||
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End point title |
Recurrence of individual Amsel criteria | |||||||||
End point description |
Number of participants with positive individual Amsel criterion
- Clue cells representing at least 20% of total epithelial cells
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End point type |
Secondary
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End point timeframe |
At or by the Week 16 visit
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Statistical analysis title |
Amsel criterion - Clue cells | |||||||||
Comparison groups |
SPL7013 Gel v Placebo Gel
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Number of subjects included in analysis |
617
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.001 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.47
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.3 | |||||||||
upper limit |
0.75 | |||||||||
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End point title |
Recurrence of BV as determined by Nugent score 7-10 | |||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
At or by the Week 16 visit
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Statistical analysis title |
Recurrence of Nugent score 7-10 | |||||||||
Comparison groups |
SPL7013 Gel v Placebo Gel
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Number of subjects included in analysis |
604
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.002 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.52
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.34 | |||||||||
upper limit |
0.78 | |||||||||
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End point title |
Recurrence of BV | |||||||||
End point description |
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)
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End point type |
Secondary
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End point timeframe |
At or by the Week 24 visit
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Statistical analysis title |
Recurrence of BV at or by Week 24 | |||||||||
Comparison groups |
SPL7013 Gel v Placebo Gel
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Number of subjects included in analysis |
636
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.068 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.74
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.53 | |||||||||
upper limit |
1.02 | |||||||||
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End point title |
Recurrence of BV according to composite of Amsel criteria and Nugent score | |||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
At or by the Week 16 visit
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Statistical analysis title |
Recurrence of BV according to composite definition | |||||||||
Comparison groups |
SPL7013 Gel v Placebo Gel
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Number of subjects included in analysis |
618
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.014 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.54
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.34 | |||||||||
upper limit |
0.88 | |||||||||
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End point title |
Adverse events (AEs) | |||||||||
End point description |
Number of participants with genitourinary AEs considered potentially related to study treatment
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End point type |
Secondary
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End point timeframe |
From Baseline to end of Week 28
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to end of study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
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Reporting groups
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Reporting group title |
SPL7013 Gel
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Gel
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
