HIV Infections
Conditions
Brief summary
The purpose of this study is to evaluate the pharmacokinetics (PK) and safety of a 90-day intravaginal ring (IVR) containing tenofovir (TFV).
Detailed description
This study will evaluate the pharmacokinetics (PK) and safety of a 90-day intravaginal ring (IVR) containing tenofovir (TFV) in healthy, HIV-uninfected individuals assigned female sex at birth. Participants will be randomly assigned to receive an IVR containing either 1.4 g TFV or placebo. The IVR will be inserted at the enrollment visit (Day 0) and used continuously for approximately 91 days. Additional study visits will occur at Days 1, 7, 14, 28, 42, 56, 91, and 92. Study visits may include behavioral assessments, physical examinations, blood and urine collection, and pelvic and rectal specimen collection.
Interventions
DRUGTenofovir (TFV) IVR
Contains 1.4 g TFV
DRUGPlacebo IVR
Contains placebo
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Assigned female sex at birth * Note: Participants who are female at birth, who now identify as male, will not be excluded so long as they are not on female-to-male transition therapy. * Age 18 through 45 years (inclusive) at Screening, verified per site standard operating procedures (SOPs) * Able and willing to provide written informed consent to be screened for and enrolled in MTN-038 * Able and willing to provide adequate locator information, as defined in site SOPs * Able to communicate in spoken and written English * Available for all visits and able and willing to comply with all study procedural requirements * Willing to abstain from receptive vaginal or anal sexual activities for 72 hours prior to each clinical visit and for 72 hours after biopsy collection * Willing to use male condoms for penile-vaginal and penile-rectal sexual intercourse for the duration of study participation * Per participant report, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment, and intending to continue use of an effective method for the duration of study participation; effective methods include: * hormonal methods (except contraceptive vaginal ring) * intrauterine device (IUD) * sterilization (of participant or partner, as defined in site SOPs) * having sex exclusively with individuals assigned female sex at birth * sexually abstinent as defined by abstaining from penile-vaginal intercourse for 90 days prior to Enrollment, and intending to remain abstinent for the duration of study participation * In general good health as determined by the Investigator of Record (IoR)/designee at Screening and Enrollment * HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithm in the study protocol) * Per participant report at Screening, regular menstrual cycles with at least 21 days between menses * Note: This criterion is not applicable to participants who report using a progestin-only method of contraception at Screening (e.g., Depo-Provera or levonorgestrel-releasing IUD) nor to participants using continuous combination oral contraceptive pills, as the absence of regular menstrual cycles is an expected, normal consequence in this context. * Per participant report at Screening and Enrollment, states a willingness to refrain from inserting any non-study vaginal and rectal products or objects into the vagina or rectum including, but not limited to spermicides, female condoms, diaphragms, intravaginal rings, vaginal or rectal medications, menstrual cups, cervical caps, douches, lubricants, and sex toys (vibrators, dildos, etc.) for the 24 hours preceding the Enrollment Visit and for the duration of study participation. * Note: Use of tampons is permitted except for 24 hours prior to clinic visits in which CVF samples are scheduled to be collected. * Participants over the age of 21 (inclusive) must have documentation of a satisfactory Pap within the past 3 years prior to Enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result * At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal or rectal products, or vaccines after the Screening Visit and for the duration of study participation
Exclusion criteria
* Pregnant at Screening or Enrollment or plans to become pregnant during the study period * Note: A documented negative pregnancy test performed by study staff is required for inclusion; however, a self-reported pregnancy is adequate for exclusion from the study. * Diagnosed with symptomatic urinary tract infection (UTI) or reproductive tract infection (RTI) at Screening or Enrollment * Otherwise eligible participants diagnosed with UTI/RTI during screening will be offered treatment. If treatment is complete and symptoms have resolved within the 45 day screening window, eligible participants may be enrolled. * Note: Asymptomatic BV and candidiasis are not exclusionary. * Diagnosed with an acute sexually transmitted infection (STI) requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines (http://www.cdc.gov/std/treatment/) at Screening or Enrollment such as gonorrhea, chlamydia, trichomonas, pelvic inflammatory disease, and/or syphilis * Note: Genital warts requiring treatment and frequent recurrence of HSV are considered exclusionary; however, infrequent HSV outbreaks are not. Genital warts requiring treatment are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort. See MTN-038 Study-Specific Procedures (SSP) Manual for additional information. * Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff) at Screening or Enrollment. \* * Note: Cervical bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the IoR/designee is considered expected non-menstrual bleeding and is not exclusionary. * Note: Otherwise eligible participants with exclusionary pelvic exam findings may be enrolled/randomized after the findings have improved to a non-exclusionary severity grading or resolved within 45 days of providing informed consent for screening. * Participant report and/or clinical evidence of any of the following: * Known adverse reaction to any of the study products (ever), including polyurethane * Chronic and/or recurrent vaginal candidiasis * Non-therapeutic injection drug use in the 12 months prior to Enrollment * Last pregnancy outcome less than 90 days prior to Enrollment * Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage, piercing) 45 days or less prior to Enrollment * Note: Colposcopy and cervical biopsies for evaluation of an abnormal Pap test as well as IUD insertion/removal are not exclusionary. * Currently breastfeeding or planning to breastfeed during the study * Participation in any other research study involving drugs, medical devices, vaginal or rectal products, or vaccines, in the 60 days prior to Enrollment * Use of pre-exposure prophylaxis (PrEP) for HIV prevention and/or post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment, and/or anticipated use and/or unwillingness to abstain from PrEP during trial participation * Has any of the following laboratory abnormalities at Screening Visit: * Grade 1 or higher Aspartate aminotransferase (AST) or alanine transaminase (ALT)\* * Grade 1 or higher Hemoglobin\* * Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula * Positive Hepatitis B surface antigen result * Note: Otherwise eligible participants with an exclusionary laboratory result may be re-tested during the screening process. If a participant is re-tested and a non-exclusionary result is documented within 45 days of providing informed consent for screening, the participant may be enrolled. * Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate the interpretation of study outcome data, or otherwise interfere with achieving the study objectives including any significant uncontrolled active or chronic medical condition. (\*) Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies \[Dated November 2007\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Grade 3 or Higher Adverse Event | Measured through Day 92 | As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 |
| Measurement of TFV Levels in Cervical Tissue | Measured through Day 92 | TFV concentrations as assessed by drug detection testing in cervical tissue samples collected at multiple timepoints during the study. |
| Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue | Measured through Day 92 | TFV-DP concentrations as assessed by drug detection testing in cervical tissue samples collected at multiple timepoints during the study. |
| Proportion of Participants With Grade 2 or Higher Genitourinary Adverse Event | Measured through Day 92 | As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, and/or Addendum 1 (Female Genital \[Dated November 2007\] Grading Table for Use in Microbicide Studies) |
| Measurement of TFV Levels in Plasma | Measured through Day 92 | TFV concentrations as assessed by drug detection testing in plasma samples collected at multiple timepoints during the study. |
| Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Measured through Day 92 | TFV concentrations as assessed by drug detection testing in CVF samples collected at multiple timepoints during the study. |
| Measurement of TFV Levels in Rectal Fluid | Measured through Day 92 | TFV concentrations as assessed by drug detection testing in rectal fluid samples collected at multiple timepoints during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration Without IVR in Vagina for Participants Not Fully Adherent | Measured through Day 92 | This includes only participants considered non-adherent. Participants were classified as fully adherent if they kept the study ring inserted at all times during the 91 days of study product use, without any product hold (according to the Product Hold Log eCRF) or ever having the ring out (by self-report in the Ring Adherence eCRF). |
| Degree to Which Participants Like or Dislike Using the IVR | Measured on the end of study, Day 92, visit. | This outcome uses question J2 Overall, how much do you like the ring? from the final product use end visit (PUEV) behavioral questionnaire. This question and one timepoint were prespecified in the Statistical Analysis Plan (SAP) section 9.2 to represent the participants' overall acceptability of the study product. The question response is on a 10-point Likert scale from 1 to 10 with 1 being extremely dislike to 10 being extremely like. A Likert scale score of 5 is neutral. |
| Number of Participants Fully Adherent to the Study IVR | Measured through Day 92 | Participants were classified as fully adherent if they kept the study ring inserted at all times during the 91 days of study product use, without any product hold (according to the Product Hold Log eCRF) or ever having the ring out (by self-report in the Ring Adherence eCRF). Ring outages could be ring removals or expulsions (voluntary or involuntary). |
Countries
United States
Participant flow
Recruitment details
49 participants were enrolled and randomized in 3 U.S. medical clinic sites from January 2, 2019 until June 25, 2019.
Pre-assignment details
49 participants were enrolled in the study and randomized to study product simultaneously.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) The TFV IVR will be inserted during the enrollment visit (Day 0) and used continuously for approximately 91 days.
Tenofovir (TFV) IVR: Contains 1.4 g TFV | 33 |
| Placebo IVR The placebo IVR will be inserted during the enrollment visit (Day 0) and used continuously for approximately 91 days.
Placebo IVR: Contains placebo | 16 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Participant refused | 0 | 1 |
| Overall Study | Unable to comply with study procedures | 0 | 1 |
Baseline characteristics
| Characteristic | Tenofovir (TFV) Intravaginal Ring (IVR) | Placebo IVR | Total |
|---|---|---|---|
| Age, Continuous | 29.0 years | 27.5 years | 29.0 years |
| Age, Customized 18-19 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Customized 20-24 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Customized 25-29 years | 8 Participants | 5 Participants | 13 Participants |
| Age, Customized 30-34 years | 7 Participants | 2 Participants | 9 Participants |
| Age, Customized 35-39 years | 7 Participants | 2 Participants | 9 Participants |
| Age, Customized 40-45 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Customized Missing | 0 Participants | 0 Participants | 0 Participants |
| Biological Gender of sex partners Both Male and Female | 4 Participants | 3 Participants | 7 Participants |
| Biological Gender of sex partners Exclusively Female Partners | 3 Participants | 2 Participants | 5 Participants |
| Biological Gender of sex partners Exclusively Male Partners | 19 Participants | 9 Participants | 28 Participants |
| Biological Gender of sex partners No Sex Partners | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 15 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Female | 33 Participants | 16 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Female | 32 Participants | 14 Participants | 46 Participants |
| Sex/Gender, Customized Gender Nonconforming/Gender Variant | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 16 |
| other Total, other adverse events | 25 / 33 | 13 / 16 |
| serious Total, serious adverse events | 0 / 33 | 0 / 16 |
Outcome results
Primary
Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue
TFV-DP concentrations as assessed by drug detection testing in cervical tissue samples collected at multiple timepoints during the study.
Time frame: Measured through Day 92
Population: This endpoint includes results from samples collected only from participants randomized to the TFV IVR arm. The samples from participants randomized to placebo will not have any TFV-DP concentrations (outcome measure) in their cervical tissue. In addition, one participant on the TFV IVR arm refused cervical tissue sample collection.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue | Day 14 postdosing | 2679.5 fmol/mg | Geometric Coefficient of Variation 82.6 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue | Day 28 postdosing | 3217.8 fmol/mg | Geometric Coefficient of Variation 85.6 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue | Day 56 postdosing | 1892.6 fmol/mg | Geometric Coefficient of Variation 178.3 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue | Day 91 postdosing | 456.2 fmol/mg | Geometric Coefficient of Variation 16735.9 |
Primary
Measurement of TFV Levels in Cervical Tissue
TFV concentrations as assessed by drug detection testing in cervical tissue samples collected at multiple timepoints during the study.
Time frame: Measured through Day 92
Population: This endpoint includes results from samples collected only from participants randomized to the TFV IVR arm. The samples from participants randomized to placebo will not have any TFV concentrations (outcome measure) in their cervical tissue. In addition, one participant on the TFV IVR arm declined collection of cervical tissue samples and is not included in the number analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervical Tissue | Day 14 postdosing | 45.9 ng/mg | Geometric Coefficient of Variation 11800.2 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervical Tissue | Day 28 postdosing | 39.1 ng/mg | Geometric Coefficient of Variation 322.8 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervical Tissue | Day 56 postdosing | 37.1 ng/mg | Geometric Coefficient of Variation 177.1 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervical Tissue | Day 91 postdosing | 6.5 ng/mg | Geometric Coefficient of Variation 254895.9 |
Primary
Measurement of TFV Levels in Cervicovaginal Fluid (CVF)
TFV concentrations as assessed by drug detection testing in CVF samples collected at multiple timepoints during the study.
Time frame: Measured through Day 92
Population: This endpoint includes results from samples collected only from participants randomized to the TFV IVR arm. The samples from participants randomized to placebo will not have any TFV concentrations (outcome measure) in their CVF.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 0, Hour 1 postdosing | 3 ng/mg | Geometric Coefficient of Variation 95.3 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 0, Hour 4 postdosing | 6.2 ng/mg | Geometric Coefficient of Variation 92.6 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 1 postdosing | 437.8 ng/mg | Geometric Coefficient of Variation 75.1 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 7 postdosing | 1468.2 ng/mg | Geometric Coefficient of Variation 129.9 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 14 postdosing | 2006.4 ng/mg | Geometric Coefficient of Variation 57.2 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 28 postdosing | 2011.8 ng/mg | Geometric Coefficient of Variation 288.6 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 56 postdosing | 2817.1 ng/mg | Geometric Coefficient of Variation 70.8 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 91 postdosing | 270.5 ng/mg | Geometric Coefficient of Variation 24859.2 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 91, 4 hours post-removal | 41.3 ng/mg | Geometric Coefficient of Variation 406784.3 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Cervicovaginal Fluid (CVF) | Day 92, 24 hours post-removal | 7.2 ng/mg | Geometric Coefficient of Variation 85571.4 |
Primary
Measurement of TFV Levels in Plasma
TFV concentrations as assessed by drug detection testing in plasma samples collected at multiple timepoints during the study.
Time frame: Measured through Day 92
Population: This endpoint includes results from samples collected only from participants randomized to the TFV IVR arm. The samples from participants randomized to placebo will not have any TFV concentrations (outcome measure) in their plasma.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 1 postdosing | 636.8 pg/mL | Geometric Coefficient of Variation 131.2 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 7 postdosing | 1915.9 pg/mL | Geometric Coefficient of Variation 102.3 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 14 postdosing | 3581.5 pg/mL | Geometric Coefficient of Variation 114.7 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 28 postdosing | 5040.7 pg/mL | Geometric Coefficient of Variation 235 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 56 postdosing | 7862.3 pg/mL | Geometric Coefficient of Variation 139.6 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 91 postdosing | 1814.6 pg/mL | Geometric Coefficient of Variation 612.2 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 91, 4 hours post-removal | 1081.2 pg/mL | Geometric Coefficient of Variation 426.9 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Plasma | Day 92, 24 hours post-removal | 236.2 pg/mL | Geometric Coefficient of Variation 127.4 |
Primary
Measurement of TFV Levels in Rectal Fluid
TFV concentrations as assessed by drug detection testing in rectal fluid samples collected at multiple timepoints during the study.
Time frame: Measured through Day 92
Population: This endpoint includes results from samples collected only from participants randomized to the TFV IVR arm. The samples from participants randomized to placebo will not have any TFV concentrations (outcome measure) in their rectal fluid.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Rectal Fluid | Day 1 postdosing | 293.6 pg/mg | Geometric Coefficient of Variation 1111 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Rectal Fluid | Day 14 postdosing | 701.8 pg/mg | Geometric Coefficient of Variation 583.2 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Rectal Fluid | Day 28 postdosing | 898.3 pg/mg | Geometric Coefficient of Variation 1355.9 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Rectal Fluid | Day 56 postdosing | 1377.3 pg/mg | Geometric Coefficient of Variation 475.9 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Rectal Fluid | Day 91 postdosing | 460.3 pg/mg | Geometric Coefficient of Variation 1093.3 |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Measurement of TFV Levels in Rectal Fluid | Day 91, 4 hours post-removal | 416.7 pg/mg | Geometric Coefficient of Variation 4315.6 |
Primary
Proportion of Participants With Grade 2 or Higher Genitourinary Adverse Event
As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, and/or Addendum 1 (Female Genital \[Dated November 2007\] Grading Table for Use in Microbicide Studies)
Time frame: Measured through Day 92
Population: Includes all participants enrolled and randomized to this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Proportion of Participants With Grade 2 or Higher Genitourinary Adverse Event | 4 Participants |
| Placebo IVR | Proportion of Participants With Grade 2 or Higher Genitourinary Adverse Event | 4 Participants |
Primary
Proportion of Participants With Grade 3 or Higher Adverse Event
As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Time frame: Measured through Day 92
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Proportion of Participants With Grade 3 or Higher Adverse Event | 0 Participants |
| Placebo IVR | Proportion of Participants With Grade 3 or Higher Adverse Event | 0 Participants |
Secondary
Degree to Which Participants Like or Dislike Using the IVR
This outcome uses question J2 Overall, how much do you like the ring? from the final product use end visit (PUEV) behavioral questionnaire. This question and one timepoint were prespecified in the Statistical Analysis Plan (SAP) section 9.2 to represent the participants' overall acceptability of the study product. The question response is on a 10-point Likert scale from 1 to 10 with 1 being extremely dislike to 10 being extremely like. A Likert scale score of 5 is neutral.
Time frame: Measured on the end of study, Day 92, visit.
Population: This outcome includes all participants who completed the final product use end visit (PUEV) behavioral questionnaire with non-missing response to question J2 Overall, how much do you like the ring?
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Degree to Which Participants Like or Dislike Using the IVR | 8 Score on a scale |
| Placebo IVR | Degree to Which Participants Like or Dislike Using the IVR | 8 Score on a scale |
Secondary
Duration Without IVR in Vagina for Participants Not Fully Adherent
This includes only participants considered non-adherent. Participants were classified as fully adherent if they kept the study ring inserted at all times during the 91 days of study product use, without any product hold (according to the Product Hold Log eCRF) or ever having the ring out (by self-report in the Ring Adherence eCRF).
Time frame: Measured through Day 92
Population: This analysis includes only participants where were not fully adherent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Duration Without IVR in Vagina for Participants Not Fully Adherent | 15.2 hours | Standard Deviation 23.1 |
| Placebo IVR | Duration Without IVR in Vagina for Participants Not Fully Adherent | 10.0 hours | Standard Deviation 14.1 |
Secondary
Number of Participants Fully Adherent to the Study IVR
Participants were classified as fully adherent if they kept the study ring inserted at all times during the 91 days of study product use, without any product hold (according to the Product Hold Log eCRF) or ever having the ring out (by self-report in the Ring Adherence eCRF). Ring outages could be ring removals or expulsions (voluntary or involuntary).
Time frame: Measured through Day 92
Population: The analysis includes all enrolled and randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tenofovir (TFV) Intravaginal Ring (IVR) | Number of Participants Fully Adherent to the Study IVR | Adherent | 28 Participants |
| Tenofovir (TFV) Intravaginal Ring (IVR) | Number of Participants Fully Adherent to the Study IVR | Non-Adherent | 5 Participants |
| Placebo IVR | Number of Participants Fully Adherent to the Study IVR | Adherent | 13 Participants |
| Placebo IVR | Number of Participants Fully Adherent to the Study IVR | Non-Adherent | 3 Participants |