HIV-1 Infections
Conditions
Keywords
HIV-1 infections
Brief summary
A double-blind, randomized, placebo-controlled Phase I/II trial to evaluate the safety of dapivirine Gel 4759, 0.05% 2.5 g and dapivirine Gel 4789, 0.05% 2.5 g formulations as compared to the vaginal HEC-based Universal placebo gel, 2.5 g in healthy HIV-negative women
Detailed description
This was a double-blind, randomized, placebo-controlled trial, to be conducted over 10 months at five research centers in the USA among 180 healthy, sexually active women, to assess the safety and acceptability of dapivirine Gel 4759, 0.05% 2.5 g, and dapivirine Gel 4789, 0.05% 2.5 g, both vaginal microbicides containing dapivirine, compared to the vaginal HEC-based Universal placebo gel, 2.5 g, containing no active ingredient, used once daily for a period of 12 weeks.
Interventions
DRUGdapivirine 4789
dapivirine gel 4789, 0.05%, 2.5g applied once daily
DRUGdapivirine gel 4759
dapivirine gel 4759, 0.05%, 2.5g applied once daily
DRUGDrug placebo
HEC-based universal placebo gel, 2.5g applied once daily
Sponsors
International Partnership for Microbicides, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Potential participants who provide inform consent will be invited to screen for the trial. All participants who consent to participate in the trial and meet specified inclusion/exclusion criteria will be invited to enrol. At enrolment women will be randomly assigned in a 1:1:1 ratio to one of three groups.
Intervention model description
All enrolled participants will apply gel on a daily basis for 12 weeks, with clinical follow-up visits at weeks 2,4,8 and 12 to monitor safety and acceptability, and a final visit 4 weeks post gel discontinuation (Visit 6, week 16) Dapivirine concentration will be measured in blood and vaginal fluid and cervical tissue.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Women 18 to 40 years of age inclusive who can give written informed consent 2. Available for all visits and consent to follow all procedures scheduled for the trial 3. Healthy and self-reported sexually active 4. HIV-negative as determined by an HIV test at time of enrollment 5. Willing to be on a stable form of contraception 6. In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle 7. Upon pelvic/speculum examination and colposcopy at the enrollment visit, the cervix and vagina appear normal as determined by qualified research center staff 8. Asymptomatic for genital infections at the time of enrollment 9. Willing to refrain from use of vaginal products or objects for 14 days prior to enrollment and for the duration of the trial. 10. Documentation of no abnormality on Pap smear within 90 days prior to randomization; 11. Willing to answer acceptability and adherence questionnaires throughout the trial 12. Willing to refrain from participation in any other research trial for the duration of this trial 13. Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures 14. Willing to abstain from all the following criteria beginning 48 hours prior to each trial visit: * Vaginal intercourse * Oral contact with her genitalia * Internal vaginal washing * Penetration of the vagina by fingers, sex toys, or any other objects, including medications 15. Willing to abstain from all of the following for 3 days after biopsy procedures: * Vaginal intercourse * Oral contact with her genitalia * Internal vaginal washing * Penetration of the vagina by fingers, sex toys, or any other objects, including medications
Exclusion criteria
1. Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening 2. Currently breast-feeding, or having breastfed within 3 months prior to screening 3. Receipt of any investigational agent within 60 days prior to screening 4. Previously participated in any HIV vaccine trial 5. Untreated urogenital infections within 2 weeks prior to enrollment 6. Presence of any abnormal physical finding on the vulva, vaginal walls or cervix during pelvic/speculum examination and/or colposcopy 7. History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, or urethral obstruction 8. Pap smear result at screening that requires cryotherapy, biopsy or treatment (other than for infection) 9. History of symptomatic or asymptomatic HSV-2 10. Any Grade 2, 3 or 4 hematology, chemistry or urinalysis laboratory abnormality at baseline 11. Unexplained, undiagnosed abnormal bleeding per vagina during or following vaginal intercourse; or urogenital surgery within 90 days prior to enrollment 12. Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex 13. Any serious acute, chronic or progressive disease 14. Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings. | 12 weeks | A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | 12 weeks | Dapivirine levels observed in plasma will be summarized using simple descriptive statistics. |
| The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 12 weeks | Adherence is defined as the percentage of participants who used the gel each day of the preceding 14 days, based on participant self reports. |
| Changes in the Vaginal pH | 12 weeks | Cervicovaginal fluid specimens will be obtained to determine vaginal pH before first gel application and at screening, enrolment and visit 5 (week 12). Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal pH in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. |
| Changes in the Vaginal Flora | 16 weeks | Cervicovaginal fluid specimens will be obtained to determine vaginal flora before first gel application and at Visits 3, 5, and 6. Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal flora in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. Nugent scores were used to assess changes in vaginal flora, and were categorized into three levels: (1) negative for BV (score: 0-3); (2) altered vaginal flora (score: 4-6); and (3) BV (score: 7-10). |
| The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c). | The distribution of dapivirine levels observed in vaginal tissue sample will be summarized using simple descriptive statistics. |
| Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 12 weeks | Acceptability was assessed as the percentage of participants at week 12 who were willing to use the gel every day if proven to prevent HIV. |
| The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c). | The distribution of dapivirine levels observed in each type of sample will be summarized using simple descriptive statistics. In addition, the proportion of women with detectable dapivirine concentrations will be calculated for each type of sample at each collection time point. Exploratory analyses of dapivirine concentration data will also be performed to take into account information reported in a diary regarding menses and tampon use throughout the trial. |
Countries
United States
Participant flow
Recruitment details
Approximately 180 women (35-50 per RC) were scheduled to be enrolled at 5 research centers in the USA. However, following IPM's decision to give priority to development of the dapivirine vaginal ring above that of dapivirine vaginal gel, the Sponsor decided to stop enrollment into IPM 020 trial after 128 participants were randomized. It was determined that the number of participants already enrolled were sufficient to allow for meaningful analysis of the data. Total trial duration was 18 months.
Participants by arm
| Arm | Count |
|---|---|
| Dapivirine Gel 4759 Will be applied by participants once daily for12-weeks treatment period
dapivirine gel 4759: dapivirine gel 4759, 0.05%, 2.5g applied once daily | 43 |
| Dapivirine Gel 4789 will be applied by participants once daily for 12-weeks treatment period
dapivirine 4789: dapivirine gel 4789, 0.05%, 2.5g applied once daily | 43 |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine Will be applied once daily for 12-weeks treatment period
Drug placebo: HEC-based universal placebo gel, 2.5g applied once daily | 42 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | discontinued use of IP due to AE, but completed visits | 0 | 0 | 1 |
| Overall Study | IP discontinued too long during BV treatment | 1 | 0 | 0 |
| Overall Study | IP dispensing error | 1 | 0 | 0 |
| Overall Study | lost 2 IP kits and did not have enough remaining to complete trial | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Not adherent | 3 | 2 | 1 |
| Overall Study | not enough IP to complete trial due to IP dispending error | 0 | 1 | 0 |
| Overall Study | participant did not attend clinic visit 6 (final visit) | 1 | 0 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Dapivirine Gel 4759 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total | Dapivirine Gel 4789 |
|---|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 5.9 | 27.5 years STANDARD_DEVIATION 5.5 | 27.6 years STANDARD_DEVIATION 5.9 | 27.5 years STANDARD_DEVIATION 5.5 |
| BMI | 28.7 kg/(m^2) STANDARD_DEVIATION 6.3 | 26.5 kg/(m^2) STANDARD_DEVIATION 6.1 | 27.6 kg/(m^2) STANDARD_DEVIATION 6.1 | 27.5 kg/(m^2) STANDARD_DEVIATION 5.9 |
| Cohabitating with main partner | 9 Participants | 12 Participants | 37 Participants | 16 Participants |
| Height | 163.7 cm STANDARD_DEVIATION 6.8 | 161.4 cm STANDARD_DEVIATION 8.9 | 162.9 cm STANDARD_DEVIATION 7.8 | 163.5 cm STANDARD_DEVIATION 7.4 |
| In a relationship with multiple partners | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| In a relationship with one partner, not married | 35 Participants | 29 Participants | 102 Participants | 38 Participants |
| Married | 9 Participants | 12 Participants | 28 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 15 Participants | 47 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 10 Participants | 4 Participants | 23 Participants | 9 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) White | 17 Participants | 18 Participants | 49 Participants | 14 Participants |
| Region of Enrollment United States | 43 participants | 42 participants | 128 participants | 43 participants |
| Sex: Female, Male Female | 43 Participants | 42 Participants | 128 Participants | 43 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 77.0 kg STANDARD_DEVIATION 17.5 | 69.2 kg STANDARD_DEVIATION 18.8 | 73.2 kg STANDARD_DEVIATION 17.3 | 73.3 kg STANDARD_DEVIATION 14.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 43 | 0 / 42 |
| other Total, other adverse events | 30 / 43 | 34 / 43 | 35 / 42 |
| serious Total, serious adverse events | 1 / 43 | 0 / 43 | 2 / 42 |
Outcome results
Primary
The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death
Time frame: 12 weeks
Population: The ITT population included all trial participants who were randomized to one of the three treatment groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dapivirine Gel 4759 | The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings. | 23 Participants |
| Dapivirine Gel 4789 | The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings. | 28 Participants |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings. | 28 Participants |
Secondary
Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
Acceptability was assessed as the percentage of participants at week 12 who were willing to use the gel every day if proven to prevent HIV.
Time frame: 12 weeks
Population: The ITT population included all trial participants who were randomized to one of the three treatment groups.~Results are reported for participants who provided questionnaire responses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dapivirine Gel 4759 | Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 24 Participants |
| Dapivirine Gel 4789 | Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 25 Participants |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 29 Participants |
Secondary
Changes in the Vaginal Flora
Cervicovaginal fluid specimens will be obtained to determine vaginal flora before first gel application and at Visits 3, 5, and 6. Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal flora in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. Nugent scores were used to assess changes in vaginal flora, and were categorized into three levels: (1) negative for BV (score: 0-3); (2) altered vaginal flora (score: 4-6); and (3) BV (score: 7-10).
Time frame: 16 weeks
Population: All participants who were assigned to a treatment group were analyzed as members of the group to which they were randomized, regardless of adherence to the planned course of treatment.~Results are reported for participants who provided vaginal samples.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 0 : Normal Flora (0-3) | 66.7 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 0 : Altered Flora (4-6) | 14.3 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 0 : Abnormal Flora (7 or more) | 19.0 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 4 : Normal Flora (0-3) | 67.6 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 4 : Altered Flora (4-6) | 8.1 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 4 : Abnormal Flora (7 or more) | 24.3 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 12: Normal Flora (0-3) | 61.8 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 12: Altered Flora (4-6) | 23.5 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 12: Abnormal Flora (7 or more) | 14.7 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Normal Flora (0-3) | 70.6 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Altered Flora (4-6) | 2.9 percentage of participants with data |
| Dapivirine Gel 4759 | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Abnormal Flora (7 or more) | 26.5 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Abnormal Flora (7 or more) | 15.2 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 0 : Normal Flora (0-3) | 60.5 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 12: Normal Flora (0-3) | 65.7 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 12: Abnormal Flora (7 or more) | 14.3 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 0 : Altered Flora (4-6) | 11.6 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 4 : Abnormal Flora (7 or more) | 32.5 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Altered Flora (4-6) | 18.2 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 0 : Abnormal Flora (7 or more) | 27.9 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 12: Altered Flora (4-6) | 20.0 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 4 : Altered Flora (4-6) | 12.5 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 4 : Normal Flora (0-3) | 55.0 percentage of participants with data |
| Dapivirine Gel 4789 | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Normal Flora (0-3) | 66.7 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 4 : Normal Flora (0-3) | 65.9 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 4 : Altered Flora (4-6) | 19.5 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Normal Flora (0-3) | 64.9 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 4 : Abnormal Flora (7 or more) | 14.6 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 12: Normal Flora (0-3) | 59.5 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 12: Altered Flora (4-6) | 24.3 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Altered Flora (4-6) | 18.9 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 0 : Normal Flora (0-3) | 54.8 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 0 : Altered Flora (4-6) | 23.8 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 12: Abnormal Flora (7 or more) | 16.2 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 0 : Abnormal Flora (7 or more) | 21.4 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal Flora | Week 16 (Follow-up after IP discontinuation): Abnormal Flora (7 or more) | 16.2 percentage of participants with data |
Secondary
Changes in the Vaginal pH
Cervicovaginal fluid specimens will be obtained to determine vaginal pH before first gel application and at screening, enrolment and visit 5 (week 12). Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal pH in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g.
Time frame: 12 weeks
Population: All participants who were assigned to a treatment group were analyzed as members of the group to which they were randomized, regardless of adherence to the planned course of treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapivirine Gel 4759 | Changes in the Vaginal pH | Visit 5 (Week 12) | 4.4 Vaginal pH | Standard Deviation 0.46 |
| Dapivirine Gel 4759 | Changes in the Vaginal pH | Visit 1 (Enrollment) | 4.45 Vaginal pH | Standard Deviation 0.52 |
| Dapivirine Gel 4759 | Changes in the Vaginal pH | Screening (Week 0) | 4.46 Vaginal pH | Standard Deviation 0.53 |
| Dapivirine Gel 4789 | Changes in the Vaginal pH | Visit 1 (Enrollment) | 4.48 Vaginal pH | Standard Deviation 0.5 |
| Dapivirine Gel 4789 | Changes in the Vaginal pH | Screening (Week 0) | 4.55 Vaginal pH | Standard Deviation 0.63 |
| Dapivirine Gel 4789 | Changes in the Vaginal pH | Visit 5 (Week 12) | 4.44 Vaginal pH | Standard Deviation 0.61 |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal pH | Screening (Week 0) | 4.55 Vaginal pH | Standard Deviation 0.95 |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal pH | Visit 5 (Week 12) | 4.38 Vaginal pH | Standard Deviation 0.47 |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Changes in the Vaginal pH | Visit 1 (Enrollment) | 4.3 Vaginal pH | Standard Deviation 0.43 |
Secondary
The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
Adherence is defined as the percentage of participants who used the gel each day of the preceding 14 days, based on participant self reports.
Time frame: 12 weeks
Population: The ITT population included all trial participants who were randomized to one of the three treatment groups.~Results are provided for participants who reported adherence information.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapivirine Gel 4759 | The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 74 percentage of participants with data |
| Dapivirine Gel 4789 | The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 73 percentage of participants with data |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 71 percentage of participants with data |
Secondary
The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point
Dapivirine levels observed in plasma will be summarized using simple descriptive statistics.
Time frame: 12 weeks
Population: The PK analysis population included all participants who received at least one dose of the active IP and for whom at least one plasma, vaginal fluid or cervical tissue sample was taken.~Results are provided for participants for whom samples were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 2 | 536.8 picograms/mililiter | Standard Deviation 297.2 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 4 | 599.5 picograms/mililiter | Standard Deviation 423.1 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 8 | 572.6 picograms/mililiter | Standard Deviation 377.5 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 12 | 519.1 picograms/mililiter | Standard Deviation 351.3 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 12 | 366.1 picograms/mililiter | Standard Deviation 329.6 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 2 | 475.8 picograms/mililiter | Standard Deviation 272.2 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 8 | 432.6 picograms/mililiter | Standard Deviation 276.8 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point | Week 4 | 446.1 picograms/mililiter | Standard Deviation 272.2 |
Secondary
The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.
The distribution of dapivirine levels observed in each type of sample will be summarized using simple descriptive statistics. In addition, the proportion of women with detectable dapivirine concentrations will be calculated for each type of sample at each collection time point. Exploratory analyses of dapivirine concentration data will also be performed to take into account information reported in a diary regarding menses and tampon use throughout the trial.
Time frame: 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
Population: The PK analysis population included all participants who received at least one dose of the active IP and for whom at least one plasma, vaginal fluid or cervical tissue sample was taken.~Results are provided for participants for whom samples were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 2 (2 weeks post-enrollment) | 467.1 nanogram/milliliter | Standard Deviation 579.8 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 3 (4 weeks post-enrolment) | 347.8 nanogram/milliliter | Standard Deviation 351.9 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 4 (8 weeks post-enrolment) | 526.9 nanogram/milliliter | Standard Deviation 580.1 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 5a (24 hours after gel discontinuation) | 192.0 nanogram/milliliter | Standard Deviation 186.7 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 5b (48 hours after gel discontinuation) | 98.63 nanogram/milliliter | Standard Deviation 180.3 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 5c (72 hours after gel discontinuation) | 177.0 nanogram/milliliter | Standard Deviation 304.9 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 5b (48 hours after gel discontinuation) | 164.0 nanogram/milliliter | Standard Deviation 233.1 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 2 (2 weeks post-enrollment) | 880.7 nanogram/milliliter | Standard Deviation 1924 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 5a (24 hours after gel discontinuation) | 680.0 nanogram/milliliter | Standard Deviation 1775 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 3 (4 weeks post-enrolment) | 462.6 nanogram/milliliter | Standard Deviation 590 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 5c (72 hours after gel discontinuation) | 245.6 nanogram/milliliter | Standard Deviation 230.7 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point. | Visit 4 (8 weeks post-enrolment) | 298.1 nanogram/milliliter | Standard Deviation 151 |
Secondary
The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point.
The distribution of dapivirine levels observed in vaginal tissue sample will be summarized using simple descriptive statistics.
Time frame: 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
Population: The PK analysis population included all participants who received at least one dose of the active IP and for whom at least one plasma, vaginal fluid or cervical tissue sample was taken.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | Visit 5a (24 hours after gel discontinuation) | 3518 nanogram/gram | Standard Deviation 3579 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | Visit 5b (48 hours after gel discontinuation) | 841.0 nanogram/gram | Standard Deviation 1582 |
| Dapivirine Gel 4759 | The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | Visit 5c (72 hours after gel discontinuation) | 4781 nanogram/gram | Standard Deviation 9161 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | Visit 5a (24 hours after gel discontinuation) | 9343 nanogram/gram | Standard Deviation 18980 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | Visit 5b (48 hours after gel discontinuation) | 1150 nanogram/gram | Standard Deviation 1184 |
| Dapivirine Gel 4789 | The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point. | Visit 5c (72 hours after gel discontinuation) | 1142 nanogram/gram | Standard Deviation 1337 |