Chlamydia Trachomatis Infection
Conditions
Brief summary
Phase 2B double-blind placebo-controlled efficacy trial of EVO100 (previously known as Amphora ® Gel) for the prevention of acquisition of urogenital Chlamydia trachomatis infection
Detailed description
Primary: To determine if intravaginal EVO100 reduces the risk of urogenital Chlamydia trachomatis (CT) infection. Secondary: To determine if intravaginal EVO100 reduces the risk of urogenital Neisseria gonorrhoeae (GC) infection. Exploratory:To determine if EVO100 use rate (subject adherence to instructed use) has an effect on proportion of subjects who experience CT or GC infection during the study intervention period. Primary Outcome Measures: Proportion of subjects who experience urogenital CT infection during the study intervention period (incident infection of CT). Secondary Outcome Measures: Proportion of subjects who experience urogenital GC infection during the study intervention period (incident infection of GC). Exploratory Outcome Measures: * Compliance with EVO100 usage during study (rate of product use adherence). * Sensitivity analyses of the primary parameter (proportion of subjects who experience at least one CT or GC infection during the study intervention period) will be performed for the following: * Subjects with ≥20%, ≥40%, ≥60% and ≥80% product use adherence * Subject Satisfaction * Sexual satisfaction
Interventions
DRUGEVO100
5 g dose applied up to 1 hour prior to coitus
DRUGPlacebo
5 g dose applied up to 1 hour prior to coitus
Sponsors
Clinical Research Management, Inc.
Evofem Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind placebo-controlled efficacy trial of EVO100
Intervention model description
Phase 2B double-blind placebo-controlled efficacy trial of EVO100 for the prevention of acquisition of urogenital Chlamydia trachomatis infection
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy female subjects between 18 and 45 years, inclusive 2. Ability to understand the consent process and procedures 3. Subjects agree to be available for all study visits 4. Written informed consent in accordance with institutional guidelines 5. Negative pregnancy test 6. Negative CT and GC NAAT tests OR positive CT or GC NAAT and receives standard of care (SOC) treatment 7. Agree to use a woman-controlled method of contraception, such as oral contraceptives, vaginal ring, birth control implants, IUDs, or tubal ligation (with the exception of spermicides, diaphragms, or any vaginally applied or inserted products containing nonoxynol-9). Condom use only is not an acceptable form of contraception for this study. 8. Able and willing to comply with all study procedures 9. Documented (as part of a retrievable medical record) CT or GC infection within 16 weeks prior to enrollment 10. Reports vaginal sexual intercourse with a male partner at least 3 times per month in the previous month and anticipates vaginal sexual intercourse regularly for the duration of the study 11. Agree to abstain from douching or any form of vaginal suppository use (other than study product) during course of study \-
Exclusion criteria
1. Participation in any study with an investigational compound or device within 30 days prior to signing informed consent 2. In the opinion of the Investigator, have a history of substance abuse in the last 12 months 3. In the opinion of the Investigator, have issues, conditions, or concerns that may compromise the safety of the subject, impact the subject's compliance with the protocol requirements, or confound the reliability of the data acquired 4. Be an Evofem, ClinicalRM, or clinical site employee regardless of direct involvement in research activities, or their close relative 5. Pregnant (or actively trying to become pregnant), or breast-feeding 6. Women who have undergone a total hysterectomy (had uterus and cervix removed) 7. Inability to provide informed consent 8. A subject with a history or expectation of noncompliance with medications or intervention protocol 9. Have engaged in sexual intercourse, douching or used of any form of vaginal suppository or intravaginal device for 24 hours prior to enrollment (may be enrolled at a later date if all other criteria are met) 10. Menstruating at enrollment (may be enrolled at a later date if all other criteria are met) 11. Women who are currently being treated, or have been treated, for a period of 14 days prior to enrollment, with specific antibiotics known to be used for the treatment of CT or GC: 1. Azithromycin 2. Erythromycin 3. Tetracycline 4. Minocycline 5. Doxycycline 6. Levofloxacin 7. Ofloxacin 8. Ceftriaxone 9. Cefixime 12. In the opinion of the Investigator, has signs/symptoms that indicate persistence of chlamydia or gonorrhea infection diagnosed at screening, new interval infection and/or a failure to comply with or complete the prescribed treatment regimen following a positive screening NAAT. 13. Women who regularly use douches, vaginal medications, products, or suppositories 14. Women who are currently using contraceptive products that are directly delivered to the vaginal mucosa, such as diaphragms, vaginal rings (e.g. NuvaRing®), spermicides, or any vaginally applied or inserted products containing nonoxynol-9. 15. Children, pregnant women, prisoners, and other vulnerable populations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urogenital CT Infection | 16 weeks | Proportion of subjects who experience urogenital CT infection during the study intervention period (incident infection of CT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urogenital GC Infection | 16 weeks | Proportion of subjects who experience urogenital GC infection during the study intervention period (incident infection of GC). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sexual Satisfaction | 16 weeks | The proportion of subjects who experienced at least one GC infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates. |
| Compliance With EVO100 and Sensitivity Analyses | 16 weeks | The proportion of subjects who experienced at least one CT infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates. |
| Compliance With EVO100 and Sensitivity Analyses (Part I) | 16 weeks | Summary of Coital Events during treatment |
| Compliance With EVO100 and Sensitivity Analyses (Part III) | 16 weeks | Study product adherence |
| Compliance With EVO100 and Sensitivity Analyses (Part II) | 16 weeks | Summary of number of applicators used via eDiary |
| Subject Satisfaction With Product | 16 weeks | The proportion of subjects who experienced at least one CT infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EVO100 A pH-buffering, acidity-maintaining gel (pH 3.5), containing three active compounds: lactic acid, citric acid, potassium bitartrate. 5 g intravaginally applied at least one hour prior to vaginal intercourse.
EVO100l: 5 g dose applied up to 1 hour prior to coitus | 426 |
| Placebo An isotonic, non-buffering gel, pH adjusted to 4.5, containing 2.7% hydroxyethylcellulose, sorbic acid, sodium hydroxide, sodium chloride and purified water. 5 g intravaginally applied at least one hour prior to vaginal intercourse.
Placebo: 5 g dose applied up to 1 hour prior to coitus | 434 |
| Total | 860 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lost to Follow-up | 37 | 34 |
| Overall Study | Other reason not specified | 16 | 15 |
| Overall Study | Physician Decision | 3 | 6 |
| Overall Study | Pregnancy | 7 | 7 |
| Overall Study | Protocol Violation | 9 | 12 |
| Overall Study | Withdrawal by Subject | 16 | 22 |
Baseline characteristics
| Characteristic | EVO100 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 426 Participants | 434 Participants | 860 Participants |
| Age, Continuous | 27.82 years STANDARD_DEVIATION 7.112 | 27.53 years STANDARD_DEVIATION 6.722 | 27.68 years STANDARD_DEVIATION 6.916 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 135 Participants | 148 Participants | 283 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 291 Participants | 286 Participants | 577 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 185 Participants | 173 Participants | 358 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 228 Participants | 239 Participants | 467 Participants |
| Region of Enrollment United States | 426 participants | 434 participants | 860 participants |
| Sex: Female, Male Female | 426 Participants | 434 Participants | 860 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 | 0 / 376 | 0 / 388 |
| other Total, other adverse events | 62 / 376 | 46 / 388 |
| serious Total, serious adverse events | 2 / 376 | 3 / 388 |
Outcome results
Primary
Urogenital CT Infection
Proportion of subjects who experience urogenital CT infection during the study intervention period (incident infection of CT).
Time frame: 16 weeks
Population: mITT Population - All CT Analysis Eligible Subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EVO100 | Urogenital CT Infection | 14 Participants |
| Placebo | Urogenital CT Infection | 28 Participants |
p-value: 0.025695% CI: [-9.02, -0.61]Chi-squared
Secondary
Urogenital GC Infection
Proportion of subjects who experience urogenital GC infection during the study intervention period (incident infection of GC).
Time frame: 16 weeks
Population: mITT Population - All GC Analysis Eligible Subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EVO100 | Urogenital GC Infection | 2 Participants |
| Placebo | Urogenital GC Infection | 9 Participants |
p-value: 0.031695% CI: [-4.84, -0.23]Chi-squared
Other Pre-specified
Compliance With EVO100 and Sensitivity Analyses
The proportion of subjects who experienced at least one GC infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates.
Time frame: 16 weeks
Population: mITT Population - All GC Analysis Eligible Subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=20% adherence | 15 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=60% adh | 40 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects w/ GC infection & >0% <20% adherence | 9 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=80% adherence | 106 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=40% adherence | 17 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & =100% adherence | 87 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & 0% adherence | 5 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & =100% adherence | 70 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & 0% adherence | 6 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects w/ GC infection & >0% <20% adherence | 7 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=20% adherence | 12 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=40% adherence | 23 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=60% adh | 36 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects with GC infection & >=80% adherence | 123 Participants |
Comparison: A comparison of infection rates between the treatment arms amongst subjects with =0% adherencep-value: 1Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>0% adherencep-value: 0.4375Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=20% adherencep-value: 0.4444Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=60% adherencep-value: 0.1836Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=80% adherencep-value: 0.5006Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with =100% adherencep-value: 1Fisher Exact
Other Pre-specified
Compliance With EVO100 and Sensitivity Analyses
The proportion of subjects who experienced at least one CT infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates.
Time frame: 16 weeks
Population: mITT Population - All CT Analysis Eligible Subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=20% adherence | 17 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=60% adhere | 41 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >0% <20% adherence | 10 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=80% adhere | 108 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=40% adherence | 19 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & =100% adhere | 86 Participants |
| EVO100 | Compliance With EVO100 and Sensitivity Analyses | # of subjects w/ CT infection & 0% adherence | 6 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & =100% adhere | 83 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | # of subjects w/ CT infection & 0% adherence | 6 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >0% <20% adherence | 7 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=20% adherence | 13 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=40% adherence | 24 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=60% adhere | 32 Participants |
| Placebo | Compliance With EVO100 and Sensitivity Analyses | of subjects w/ CT infection & >=80% adhere | 125 Participants |
Comparison: A comparison of infection rates between the treatment arms amongst subjects with =0% adherencep-value: 1Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>0% adherencep-value: 1Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=20% adherencep-value: 0.6278Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=40% adherencep-value: 0.6404Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=60% adherencep-value: 0.5008Fisher Exact
Comparison: A comparison of infection rates between the treatment arms amongst subjects with \>=80% adherencep-value: 0.1818Chi-squared
Comparison: A comparison of infection rates between the treatment arms amongst subjects with =100% adherencep-value: 0.0012Chi-squared
Other Pre-specified
Compliance With EVO100 and Sensitivity Analyses (Part I)
Summary of Coital Events during treatment
Time frame: 16 weeks
Population: mITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EVO100 | Compliance With EVO100 and Sensitivity Analyses (Part I) | 15.7 Coital Events | Standard Deviation 14.38 |
| Placebo | Compliance With EVO100 and Sensitivity Analyses (Part I) | 16.3 Coital Events | Standard Deviation 15.79 |
Other Pre-specified
Compliance With EVO100 and Sensitivity Analyses (Part II)
Summary of number of applicators used via eDiary
Time frame: 16 weeks
Population: mITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EVO100 | Compliance With EVO100 and Sensitivity Analyses (Part II) | 13.0 Number of Applicators | Standard Deviation 12.95 |
| Placebo | Compliance With EVO100 and Sensitivity Analyses (Part II) | 13.5 Number of Applicators | Standard Deviation 15.18 |
Other Pre-specified
Compliance With EVO100 and Sensitivity Analyses (Part III)
Study product adherence
Time frame: 16 weeks
Population: mITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EVO100 | Compliance With EVO100 and Sensitivity Analyses (Part III) | 78.9 % of sex acts where study product used | Standard Deviation 27.14 |
| Placebo | Compliance With EVO100 and Sensitivity Analyses (Part III) | 78.3 % of sex acts where study product used | Standard Deviation 27.78 |
Other Pre-specified
Sexual Satisfaction
The proportion of subjects who experienced at least one GC infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates.
Time frame: 16 weeks
Population: Subjects sexual satisfaction by Visit - mITT population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EVO100 | Sexual Satisfaction | My sex life is a little better than before | 75 Participants |
| EVO100 | Sexual Satisfaction | My sex life is a little worse than before | 8 Participants |
| EVO100 | Sexual Satisfaction | My sex life is no different than before | 124 Participants |
| EVO100 | Sexual Satisfaction | My sex life is a lot worse than before | 1 Participants |
| EVO100 | Sexual Satisfaction | My sex life is a lot better than before | 65 Participants |
| Placebo | Sexual Satisfaction | My sex life is a lot worse than before | 0 Participants |
| Placebo | Sexual Satisfaction | My sex life is a lot better than before | 53 Participants |
| Placebo | Sexual Satisfaction | My sex life is a little better than before | 73 Participants |
| Placebo | Sexual Satisfaction | My sex life is no different than before | 137 Participants |
| Placebo | Sexual Satisfaction | My sex life is a little worse than before | 4 Participants |
Other Pre-specified
Subject Satisfaction With Product
The proportion of subjects who experienced at least one CT infection during the study Intervention Period was summarized by treatment group using the mITT population and subject adherence rates.
Time frame: 16 weeks
Population: Subject Satisfaction by Visit (mITT population)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EVO100 | Subject Satisfaction With Product | Satisfied | 128 Participants |
| EVO100 | Subject Satisfaction With Product | Somewhat dissatisfied | 5 Participants |
| EVO100 | Subject Satisfaction With Product | Somewhat Satisfied | 26 Participants |
| EVO100 | Subject Satisfaction With Product | Dissatisfied | 1 Participants |
| EVO100 | Subject Satisfaction With Product | Very satisfied | 113 Participants |
| Placebo | Subject Satisfaction With Product | Dissatisfied | 0 Participants |
| Placebo | Subject Satisfaction With Product | Very satisfied | 119 Participants |
| Placebo | Subject Satisfaction With Product | Satisfied | 121 Participants |
| Placebo | Subject Satisfaction With Product | Somewhat Satisfied | 24 Participants |
| Placebo | Subject Satisfaction With Product | Somewhat dissatisfied | 3 Participants |