Safety and Efficacy of Oral Encochleated Amphotericin B (CAMB/MAT2203) in the Treatment of Vulvovaginal Candidiasis (VVC)

• Sponsor: Matinas BioPharma Nanotechnologies, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02971007
• Collaborator: (none)
• Enrollment: 137
• Locations: 23
• Arms: 3
• Actual Duration (Months): 5.9
• Patients Per Site: 6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This is a multi-center, randomized study to evaluate the safety, tolerability, and efficacy of 200 mg CAMB and 400 mg CAMB compared with a single 150 mg dose of fluconazole in the treatment of moderate to severe VVC.

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginitis; Yeast Infection; Yeast Infection Vaginal; Candidiasis, Vulvovaginal	Drug: Oral Encochleated Amphotericin B (CAMB); Drug: Fluconazole	Phase 2

Detailed Description

This is a multi-center, randomized study to evaluate the safety, tolerability, and efficacy of 200 mg CAMB and 400 mg CAMB compared with a single 150 mg dose of fluconazole in the treatment of moderate to severe VVC.

Approximately 75 women with moderate to severe VVC will be randomized to 1 of 3 treatment groups (200 mg CAMB, 400 mg CAMB, or fluconazole) to achieve approximately 25 subjects in each group. The primary objective of this study is to evaluate the safety of 200 mg and 400 mg doses of oral CAMB for 5 days compared with a single 150 mg dose of oral fluconazole in subjects with moderate to severe VVC. The secondary efficacy objectives of this study included the clinical cure rate, mycology eradication and responder outcome. Tertiary objectives include pharmacokinetics.

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Randomized Study to Evaluate the Safety, Tolerability, and Efficacy of Oral Encochleated Amphotericin B (CAMB/MAT2203) Compared With Oral Fluconazole in the Treatment of Moderate to Severe Vulvovaginal Candidiasis (VVC)
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAMB 200 mg 200 mg CAMB (MAT2203) Oral Amphotericin B	Drug: Oral Encochleated Amphotericin B (CAMB); lipid-crystal nano-particle formulation amphotericin B; Other Names: MAT2203
Experimental: CAMB 400 mg 400 mg CAMB (MAT2203) Oral Amphotericin B	Drug: Oral Encochleated Amphotericin B (CAMB); lipid-crystal nano-particle formulation amphotericin B; Other Names: MAT2203
Active Comparator: Fluconazole 150 mg Fluconazole Diflucan	Drug: Fluconazole

Outcome Measures

Primary Outcome Measures

1. Clinical Outcome Assessed at Test of Cure Visit [12 days]

   Number of patients determined to be a Clinical Cure (resolution of the VVC signs and symptoms that were present at baseline without further antifungal treatment); Clinical Failure (incomplete resolution of signs and symptoms of VVC that were present at baseline or new signs and symptoms have developed and require the initiation of non-study antifungal drugs); or Clinical indeterminate (insufficient data are available to determine if the subject is a cure or failure)

Secondary Outcome Measures

1. Mycological Outcome Assessed at Test of Cure [12 days]

   Number of patients with mycological eradication (vaginal swab culture negative for growth of baseline Candida species); mycological persistence (vaginal swab culture positive for growth of baseline Candida species); or mycological indeterminate (vaginal swab culture not available or the culture cannot be interpreted or is considered contaminated)

2. Overall Response [12 Days]

   Number of patients with overall response at Day 12 (Test of cure visit) of composite signs and symptoms defined as overall success (achievement of both a clinical cure and microbiological eradication); overall failure (clinical failure or microbiological persistence) or overall indeterminate (insufficient data are available to determine if the patient is an overall success or failure).

3. Change in Composite Clinical Cure Score [Between randomization visit (Baseline) and Day 12 visit (Test of Cure)]

   The percent change from baseline to Day 12 (Test of Cure Visit) of the composite clinical cure score of signs (erythema, edema or excoriation) and symptoms (itching, burning or irritation) on a scale of 0 to 3 for each sign and symptom where 0 = none (complete absence of any sign or symptom); 1 = mild (slight); 2 = moderate (definitely present) or 3 = severe (marked/intense). The maximum score at baseline = 18 (score of 3 for each sign and symptom). The minimum score at baseline = 4 (score of 2 for at least 2 signs or symptoms). A lower score at Day 12 represents a better outcome. The mean percent change from baseline score to Day 12 score is presented for each arm as a negative number and represents a decrease in severity of signs and symptoms. A bigger decrease represents a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

Informed consent

Clinical diagnosis of moderate to severe VVC

Negative pregnancy test

Vaginal pH less than 4.5

Key Exclusion Criteria:

Has an intolerance or hypersensitivity to any amphotericin B (AMB) product, or to azole antifungal drugs

Receiving antifungal therapy unrelated to VVC or has evidence of systemic fungal infections requiring antifungal therapy

Has received treatment for VVC within the past 30 days or has experienced 4 or more episodes of VVC in the past 12 months

Has another cause of vulvovaginitis

Has other urogenital infection(s) that would potentially alter their response to disease

Has another vaginal or vulvar condition that would confound the interpretation of clinical response

Has significant laboratory abnormality at screening

Has any known azole-resistant Candida infection;

Has any other condition the Investigator believes would interfere with the subject's ability to provide informed consent, comply with study instructions, or puts the subject at undue risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Therapeutics	Birmingham	Alabama	United States	35205
2	Precision Trials, LLC	Phoenix	Arizona	United States	85032
3	National Research Institute - Wilshire	Los Angeles	California	United States	90057
4	South Florida Medical Research	Aventura	Florida	United States	33180
5	Neostart Corporation dba AGA Clinical Trials	Hialeah	Florida	United States	33012
6	Altus Research	Lake Worth	Florida	United States	33461
7	Advanced Research Institute Inc	New Port Richey	Florida	United States	34653
8	Healthcare Clinical Data, Inc.	North Miami	Florida	United States	33161
9	Clinical Research of West Florida - Tampa	Tampa	Florida	United States	33603
10	Visions Clinical Research	Wellington	Florida	United States	33414
11	Mt. Vernon Clinical Research - Wake Research	Atlanta	Georgia	United States	30328
12	Brighton Clinical Research Associates	Norcross	Georgia	United States	30092
13	Medpharmics	Metairie	Louisiana	United States	70006
14	New England Center for Clinical Research, Inc.	Fall River	Massachusetts	United States	02720
15	Lawrence OB/GYN	Lawrenceville	New Jersey	United States	08648
16	ProHEALTH Care Associates, LLC - Suffolk OB-GYN	Port Jefferson	New York	United States	11777
17	PMG Research of Salisbury, LLC.	Salisbury	North Carolina	United States	28144
18	PMG Research of Wilmington, LLC	Wilmington	North Carolina	United States	28401
19	Complete Health Care for Women	Columbus	Ohio	United States	43231
20	Study Center	Columbus	Ohio	United States	43231
21	Jackson Clinic	Jackson	Tennessee	United States	38305
22	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
23	Tidewater Clinical Research, Inc.	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Matinas BioPharma Nanotechnologies, Inc.

Investigators

• Study Director: Douglas Kling, Matinas BioPharma Nanotechnologies, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 30, 2017

More Information

Publications

None provided.

• Responsible Party: Matinas BioPharma Nanotechnologies, Inc.
• ClinicalTrials.gov Identifier: NCT02971007
• Other Study ID Numbers: MB-70005
• First Posted: Nov 22, 2016
• Last Update Posted: Nov 2, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Candidiasis; Candidiasis, Vulvovaginal; Mycoses; Vulvovaginitis; Fluconazole; Amphotericin B; Liposomal amphotericin B

Study Results

Participant Flow

Recruitment Details	Recruitment period November 2016 to May 2017 at 22 medical clinics in USA
Pre-assignment Detail	Enrolled patients were excluded from the study before assignment to groups due to abnormal laboratory test results, negative potassium hydroxide test (KOH) for vaginal yeast or vaginal pH greater than 4.5 during the screening process.

Arm/Group Title	CAMB 200 mg	CAMB 400 mg	Fluconazole 150 mg
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	Fluconazole Diflucan Fluconazole
Period Title: Overall Study
STARTED	46	45	46
COMPLETED	44	42	45
NOT COMPLETED	2	3	1

Baseline Characteristics

Arm/Group Title	CAMB 200 mg	CAMB 400 mg	Fluconazole 150 mg	Total
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	Fluconazole Diflucan Fluconazole	Total of all reporting groups
Overall Participants	46	45	46	137
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.7 (12.63)	36.2 (9.77)	34.3 (11.25)	35.4 (11.24)
Sex: Female, Male (Count of Participants)
Female	46 100%	45 100%	46 100%	137 100%
Male	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 43.5%	14 31.1%	9 19.6%	43 31.4%
Not Hispanic or Latino	26 56.5%	31 68.9%	37 80.4%	94 68.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 26.1%	22 48.9%	24 52.2%	58 42.3%
White	34 73.9%	23 51.1%	22 47.8%	79 57.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	46 100%	45 100%	46 100%	137 100%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	30.49 (8.136)	30.64 (8.411)	29.50 (6.973)	30.21 (7.819)

Outcome Measures

1. Primary Outcome

Title	Clinical Outcome Assessed at Test of Cure Visit
Description	Number of patients determined to be a Clinical Cure (resolution of the VVC signs and symptoms that were present at baseline without further antifungal treatment); Clinical Failure (incomplete resolution of signs and symptoms of VVC that were present at baseline or new signs and symptoms have developed and require the initiation of non-study antifungal drugs); or Clinical indeterminate (insufficient data are available to determine if the subject is a cure or failure)
Time Frame	12 days

Outcome Measure Data

Analysis Population Description

All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline

Arm/Group Title	CAMB 200 mg	CAMB 400 mg	Fluconazole 150 mg
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	Fluconazole Diflucan Fluconazole
Measure Participants	25	22	32
Clinical Cure	13 28.3%	12 26.7%	24 52.2%
Clinical Failure	12 26.1%	8 17.8%	7 15.2%
Clinical Indeterminate	0 0%	2 4.4%	1 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAMB 200 mg, CAMB 400 mg, Fluconazole 150 mg
	Comments	No formal sample size calculations were made. The sample size was determined empirically rather than with a specific statistical rationale and is considered sufficient to achieve the study objectives of this proof of concept study. Women with moderate to severe Vulvovaginal candidiasis were randomized in a 1:1:1 ratio to 1 of 3 treatment groups, stratified by signs and symptoms composite score of up to 12 (moderate) and greater than 13 (severe).
	Type of Statistical Test	Other
	Comments	Statistical analyses primarily descriptive with no formal statistical hypothesis testing. Summary statistics are presented by treatment group. For continuous variables, the number of observations, mean, standard deviation, median, minimum and maximum are provided as summary statistics.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Statistical analyses primarily descriptive with no formal statistical hypothesis testing. Summary statistics are presented by treatment group. For continuous variables, the number of observations, mean, standard deviation, median, minimum and maximum are provided as summary statistics.

2. Secondary Outcome

Title	Mycological Outcome Assessed at Test of Cure
Description	Number of patients with mycological eradication (vaginal swab culture negative for growth of baseline Candida species); mycological persistence (vaginal swab culture positive for growth of baseline Candida species); or mycological indeterminate (vaginal swab culture not available or the culture cannot be interpreted or is considered contaminated)
Time Frame	12 days

Outcome Measure Data

Analysis Population Description

All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline

Arm/Group Title	CAMB 200 mg	CAMB 400 mg	Fluconazole 150 mg
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	Fluconazole Diflucan Fluconazole
Measure Participants	25	22	32
Mycological Eradication	9 19.6%	7 15.6%	27 58.7%
Mycological Persistence	16 34.8%	13 28.9%	4 8.7%
Mycological Indeterminate	0 0%	2 4.4%	1 2.2%

3. Secondary Outcome

Title	Overall Response
Description	Number of patients with overall response at Day 12 (Test of cure visit) of composite signs and symptoms defined as overall success (achievement of both a clinical cure and microbiological eradication); overall failure (clinical failure or microbiological persistence) or overall indeterminate (insufficient data are available to determine if the patient is an overall success or failure).
Time Frame	12 Days

Outcome Measure Data

Analysis Population Description

All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline

Arm/Group Title	CAMB 200 mg	CAMB 400 mg	Fluconazole 150 mg
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	Fluconazole Diflucan Fluconazole
Measure Participants	25	22	32
Overall Success	4 8.7%	3 6.7%	22 47.8%
Overall Failure	21 45.7%	17 37.8%	9 19.6%
Overall Indeterminate	0 0%	2 4.4%	1 2.2%

4. Secondary Outcome

Title	Change in Composite Clinical Cure Score
Description	The percent change from baseline to Day 12 (Test of Cure Visit) of the composite clinical cure score of signs (erythema, edema or excoriation) and symptoms (itching, burning or irritation) on a scale of 0 to 3 for each sign and symptom where 0 = none (complete absence of any sign or symptom); 1 = mild (slight); 2 = moderate (definitely present) or 3 = severe (marked/intense). The maximum score at baseline = 18 (score of 3 for each sign and symptom). The minimum score at baseline = 4 (score of 2 for at least 2 signs or symptoms). A lower score at Day 12 represents a better outcome. The mean percent change from baseline score to Day 12 score is presented for each arm as a negative number and represents a decrease in severity of signs and symptoms. A bigger decrease represents a better outcome.
Time Frame	Between randomization visit (Baseline) and Day 12 visit (Test of Cure)

Outcome Measure Data

Analysis Population Description

All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline

Arm/Group Title	CAMB 200 mg	CAMB 400 mg	Fluconazole 150 mg
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B	Fluconazole Diflucan Fluconazole
Measure Participants	25	22	32
Mean (Standard Deviation) [percent change]	-80.9 (24.63)	-80.1 (44.66)	-94.0 (13.71)

Adverse Events

Time Frame	Adverse event data collected from randomization through follow-up phone call between Day 21 to Day 30.
Arm/Group Title	CAMB 200 mg		CAMB 400 mg		Fluconazole 150 mg
Arm/Group Description	200 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B		400 mg CAMB (MAT2203) Oral Amphotericin B Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B		Fluconazole Diflucan Fluconazole
All Cause Mortality
	CAMB 200 mg		CAMB 400 mg		Fluconazole 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/45 (0%)		0/46 (0%)
Serious Adverse Events
	CAMB 200 mg		CAMB 400 mg		Fluconazole 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/45 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	CAMB 200 mg		CAMB 400 mg		Fluconazole 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/46 (21.7%)		12/45 (26.7%)		4/46 (8.7%)
Gastrointestinal disorders
Diarrhoea	2/46 (4.3%)	2	3/45 (6.7%)	3	0/46 (0%)	0
Nausea	3/46 (6.5%)	3	2/45 (4.4%)	2	1/46 (2.2%)	1
Infections and infestations
Bacterial Vaginosis	3/46 (6.5%)	3	5/45 (11.1%)	5	2/46 (4.3%)	2
Urinary Tract Infection	2/46 (4.3%)	2	2/45 (4.4%)	2	1/46 (2.2%)	1

Limitations/Caveats

This is a proof of concept study not designed or powered to support an indication for the treatment of VVC but to establish safety, tolerability and efficacy in a non-life threatening fungal infection.

More Information

Certain Agreements

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

Data may be considered for publication in a scientific journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data pertaining to the study confidential and must consult with the Sponsor before any study data are submitted for publication. Sponsor reserves the right to deny publication rights until mutual agreement on the content, format, interpretation of data in the manuscript, and journal selected for publication are achieved.