A Phase 3 Study of SYM-1219 Treatment of Women and Post-Menarchal Adolescent Girls With Bacterial Vaginosis

• Sponsor: Symbiomix Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02418845
• Collaborator: (none)
• Enrollment: 189
• Locations: 21
• Arms: 2
• Actual Duration (Months): 6.3
• Patients Per Site: 9
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this clinical trial is to test the safety and efficacy of the oral investigational new drug, SYM-1219 for the treatment of bacterial vaginosis.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Vaginosis	Drug: SYM-1219; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multi-center, Prospective, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effectiveness and Safety of SYM-1219 2 Grams for the Treatment of Women and Post-Menarchal Adolescent Girls With Bacterial Vaginosis
• Actual Study Start Date: May 28, 2015
• Actual Primary Completion Date: Oct 5, 2015
• Actual Study Completion Date: Dec 5, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SYM-1219 Administered orally	Drug: SYM-1219
Placebo Comparator: Placebo Administered orally	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Clinical Outcome Responder Rate [Study Days 21-30 (End of Study (EOS))]

   Determined by Normal vaginal discharge, negative 10% KOH Whiff test, & Clue cells less than 20%

Secondary Outcome Measures

1. Clinical Outcome Responder Rate (Interim Visit Only) [Study Days 7-14 (interim)]

   Determined by Normal vaginal discharge, negative 10% KOH Whiff test, & Clue cells less than 20%

2. Gram Stain Slide Nugent Score [Study Days 7-14 (interim) & Study Days 21-30 End of Study (EOS)]

   A score of 0-3 will be considered normal; a score of 4 and above will be considered abnormal

3. Therapeutic Outcome Responder Rate [Study days 7-14 (interim) & study days 21-30 (EOS)]

   A Therapeutic Outcome Responder is defined as a Clinical Outcome Responder with a normal Nugent Score (between 0-3)

4. Investigator's Clinical Assessment [Study days 21-30 End of Study (EOS)]

   Investigator's opinion of the need for additional Bacterial Vaginosis (BV) treatment (Yes or No)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are premenopausal adult females or post menarchal adolescent girls ≥12 years of age in good general health

• Have a clinical diagnosis of bacterial vaginosis, defined as having all of the following criteria:

• Off-white (milky or gray), thin, homogeneous vaginal discharge

• Vaginal pH ≥ 4.7

• Presence of Clue cells of ≥ 20% of the total epithelial cells on microscopic examination of the vaginal saline wet mount

• A positive 10% KOH Whiff test

• Have a Gram stain slide Nugent Score ≥ 4 at the Baseline Visit (Day 1)

Exclusion Criteria:

• Are pregnant, lactating, or planning to become pregnant during the study

• Are menstruating or have vaginal bleeding at the Baseline Visit (Day 1)

• Are suspected clinically (or confirmed diagnostically) of having alternative causes of vaginal symptoms including candidiasis, Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae or Herpes simplex

• Have received antifungal or antimicrobial therapy (systemic or intravaginal) within 14 days prior to the Baseline Visit (Day 1)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35294
2		Jonesboro	Arkansas	United States	72401
3		San Diego	California	United States	92108
4		Colorado Springs	Colorado	United States	80910
5		Denver	Colorado	United States	80209
6		Leesburg	Florida	United States	34748
7		Miami	Florida	United States	33161
8		Wellington	Florida	United States	33414
9		Atlanta	Georgia	United States	30312
10		Baltimore	Maryland	United States	21224
11		Grand Rapids	Michigan	United States	49503
12		Plainsboro	New Jersey	United States	08536
13		New Bern	North Carolina	United States	28562
14		Columbus	Ohio	United States	73212
15		Philadelphia	Pennsylvania	United States	19107
16		Philadelphia	Pennsylvania	United States	19114
17		Myrtle Beach	South Carolina	United States	29572
18		Corpus Christi	Texas	United States	78414
19		Houston	Texas	United States	77054
20		Virginia Beach	Virginia	United States	23456
21		Seattle	Washington	United States	98105

Sponsors and Collaborators

• Symbiomix Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Symbiomix Therapeutics
• ClinicalTrials.gov Identifier: NCT02418845
• Other Study ID Numbers: SYM-1219-301
• First Posted: Apr 16, 2015
• Last Update Posted: Oct 15, 2021
• Last Verified: Sep 1, 2021

• Additional relevant MeSH terms: Vaginosis, Bacterial; Vaginal Diseases

Study Results

Participant Flow

Recruitment Details	Female post-menarchal participants age 12 and older, inclusive, with a clinical diagnosis of bacterial vaginosis were recruited and enrolled in 21 investigative medical sites throughout the US. Recruitment/enrollment took place between May 4, 2015 and Sep 24, 2015.

Arm/Group Title	SYM-1219	Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo
Period Title: Overall Study
STARTED	125	64
COMPLETED	109	52
NOT COMPLETED	16	12

Baseline Characteristics

Arm/Group Title	SYM-1219	Placebo	Total
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo	Total of all reporting groups
Overall Participants	125	64	189
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	125 100%	64 100%	189 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	125 100%	64 100%	189 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 16.8%	12 18.8%	33 17.5%
Not Hispanic or Latino	104 83.2%	52 81.3%	156 82.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.8%	1 1.6%	2 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	67 53.6%	33 51.6%	100 52.9%
White	55 44%	29 45.3%	84 44.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.6%	1 1.6%	3 1.6%
Region of Enrollment (participants) [Number]
United States	125 100%	64 100%	189 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Outcome Responder Rate
Description	Determined by Normal vaginal discharge, negative 10% KOH Whiff test, & Clue cells less than 20%
Time Frame	Study Days 21-30 (End of Study (EOS))

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population includes all randomized participants who met all inclusion/exclusion criteria.

Arm/Group Title	SYM-1219	Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo
Measure Participants	107	57
Clinical Outcome Responder	57 45.6%	11 17.2%
Non-Responder	50 40%	46 71.9%

2. Secondary Outcome

Title	Clinical Outcome Responder Rate (Interim Visit Only)
Description	Determined by Normal vaginal discharge, negative 10% KOH Whiff test, & Clue cells less than 20%
Time Frame	Study Days 7-14 (interim)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population includes all randomized participants who met all inclusion/exclusion criteria

Arm/Group Title	SYM-1219	Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo
Measure Participants	107	57
Clinical Outcome Responder	62 49.6%	14 21.9%
Non-Responder	45 36%	43 67.2%

3. Secondary Outcome

Title	Gram Stain Slide Nugent Score
Description	A score of 0-3 will be considered normal; a score of 4 and above will be considered abnormal
Time Frame	Study Days 7-14 (interim) & Study Days 21-30 End of Study (EOS)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population includes all randomized participants who met all inclusion/exclusion criteria.

Arm/Group Title	SYM-1219	Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo
Measure Participants	107	57
Nugent Score 0-3	49 39.2%	2 3.1%
Nugent Score 4 or greater	58 46.4%	55 85.9%
Nugent Score 0-3	47 37.6%	3 4.7%
Nugent Score 4 or greater	60 48%	54 84.4%

4. Secondary Outcome

Title	Therapeutic Outcome Responder Rate
Description	A Therapeutic Outcome Responder is defined as a Clinical Outcome Responder with a normal Nugent Score (between 0-3)
Time Frame	Study days 7-14 (interim) & study days 21-30 (EOS)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population includes all randomized participants who met all inclusion/exclusion criteria.

Arm/Group Title	SYM-1219	Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo
Measure Participants	107	57
Therapeutic Outcome Responder	37 29.6%	2 3.1%
Non-Responder	70 56%	55 85.9%
Therapeutic Outcome Responder	37 29.6%	2 3.1%
Non-Responder	70 56%	55 85.9%

5. Secondary Outcome

Title	Investigator's Clinical Assessment
Description	Investigator's opinion of the need for additional Bacterial Vaginosis (BV) treatment (Yes or No)
Time Frame	Study days 21-30 End of Study (EOS)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population includes all randomized participants who met all inclusion/exclusion criteria.

Arm/Group Title	SYM-1219	Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219	Administered orally as a single dose Placebo
Measure Participants	107	57
Additional BV treatment needed	32 25.6%	38 59.4%
No additional treatment needed	68 54.4%	16 25%
Missing	7 5.6%	3 4.7%

Adverse Events

Arm/Group Title	SYM-1219		Placebo
Arm/Group Description	2 grams administered orally as a single dose SYM-1219		Administered orally as a single dose Placebo
All Cause Mortality
	SYM-1219		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		0/64 (0%)
Serious Adverse Events
	SYM-1219		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/125 (1.6%)		0/64 (0%)
Nervous system disorders
Syncope	1/125 (0.8%)	1	0/64 (0%)	0
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	1/125 (0.8%)	1	0/64 (0%)	0
Other (Not Including Serious) Adverse Events
	SYM-1219		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/125 (34.4%)		14/64 (21.9%)
Gastrointestinal disorders
Nausea	6/125 (4.8%)		1/64 (1.6%)
Diarrhoea	5/125 (4%)		1/64 (1.6%)
Abdominal pain	4/125 (3.2%)		2/64 (3.1%)
Vomiting	3/125 (2.4%)		0/64 (0%)
Constipation	2/125 (1.6%)		0/64 (0%)
Dry mouth	1/125 (0.8%)		0/64 (0%)
Dyspepsia	1/125 (0.8%)		0/64 (0%)
Gastroesophageal reflux disease	1/125 (0.8%)		0/64 (0%)
Toothache	1/125 (0.8%)		0/64 (0%)
General disorders
Fatigue	1/125 (0.8%)		0/64 (0%)
Pyrexia	1/125 (0.8%)		0/64 (0%)
Infections and infestations
Vulvovaginal mycotic infection	9/125 (7.2%)		2/64 (3.1%)
Vulvovaginal candidiasis	8/125 (6.4%)		1/64 (1.6%)
Bronchitis	1/125 (0.8%)		0/64 (0%)
Folliculitis	1/125 (0.8%)		0/64 (0%)
Oral candidiasis	1/125 (0.8%)		0/64 (0%)
Subcutaneous abcess	1/125 (0.8%)		0/64 (0%)
Urinary tract infection	1/125 (0.8%)		2/64 (3.1%)
Investigations
Alanine aminotransferase increased	0/125 (0%)		1/64 (1.6%)
Metabolism and nutrition disorders
Dehydration	2/125 (1.6%)		0/64 (0%)
Decreased appetite	1/125 (0.8%)		0/64 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/125 (0.8%)		0/64 (0%)
Nervous system disorders
Headache	6/125 (4.8%)		2/64 (3.1%)
Dizziness	2/125 (1.6%)		0/64 (0%)
Syncope	1/125 (0.8%)		0/64 (0%)
Dysgeusia	1/125 (0.8%)		0/64 (0%)
Somnolence	1/125 (0.8%)		0/64 (0%)
Psychiatric disorders
Anxiety	1/125 (0.8%)		0/64 (0%)
Renal and urinary disorders
Chromaturia	1/125 (0.8%)		0/64 (0%)
Reproductive system and breast disorders
Vulvovaginal pruritis	3/125 (2.4%)		2/64 (3.1%)
Vaginal haemorrhage	2/125 (1.6%)		0/64 (0%)
Menstruation irregular	1/125 (0.8%)		0/64 (0%)
Pelvic pain	1/125 (0.8%)		0/64 (0%)
Vulvovaginal erythema	1/125 (0.8%)		0/64 (0%)
Metrorrhagia	0/125 (0%)		1/64 (1.6%)
Vulvovaginal discomfort	0/125 (0%)		2/64 (3.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/125 (0.8%)		0/64 (0%)
Oropharyngeal pain	1/125 (0.8%)		0/64 (0%)
Sinus congestion	0/125 (0%)		1/64 (1.6%)
Skin and subcutaneous tissue disorders
Acne	1/125 (0.8%)		0/64 (0%)
Blister	1/125 (0.8%)		0/64 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI submits complete copy of publication material to sponsor at least 60 days prior to submission implementing all reasonable sponsor comments. If sponsor determines that proposed publication contains disclosure of intellectual property for which sponsor is seeking patent protection, PI shall delay submission 60 days from sponsor notice so sponsor may file patent application covering intellectual property. PI shall have no further rights to publish sponsor confidential information.