HIV Prevention
Conditions
Keywords
Acceptability, Rectal microbicide
Brief summary
MTN-035 is a multi-site, randomized-sequence, three-period, open label crossover study that will enroll approximately 210 participants randomized (1:1:1:1:1:1) to one of six sequences of rectal microbicide placebo product application.
Detailed description
MTN-035 is a multi-site, randomized-sequence, three-period, open label crossover study that will enroll approximately 210 participants randomized (1:1:1:1:1:1) to one of six sequences of rectal microbicide placebo product application. At the start of each 4-week product use period, participants will receive either rectal inserts, rectal douches, or rectal suppositories and be instructed to use their assigned study product prior to each receptive anal intercourse (RAI) encounter during that period. Participants who do not have RAI in a given week will be asked to use the product without sex. There will be a 1-week washout period between each of the three product use periods. Participant follow-up will take approximately 3.5 months.
Interventions
BEHAVIORALPlacebo rectal insert
Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.
BEHAVIORALPlacebo rectal suppository
Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.
BEHAVIORALPlacebo rectal douche
Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
Microbicide Trials Network
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
1. Men (cis or transgender) and TGW who are 18-35 years old at Screening, verified per site SOP. 2. Able and willing to provide written informed consent. 3. HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results. 4. Able and willing to provide adequate locator information, as defined in site SOP. 5. Available to return for all study visits and willing to comply with study participation requirements. 6. In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee. 7. At Screening, history of consensual RAI at least three times in the past three months and expecting to maintain at least this frequency of RAI during study participation per participant report. 8. Willing to not take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation (including the time between Screening and Enrollment). 9. For individuals who can get pregnant (i.e., TGM with a female reproductive system): a negative pregnancy test at Screening and Enrollment. 10. For individuals who can get pregnant: Per participant report at Enrollment, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment and intending to use an effective method for the duration of study participation; effective methods include: 1. Hormonal methods; 2. Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions); 3. Sterilization (of participant or, if in a monogamous relationship, of partner, as defined in site SOPs); 4. Abstinence from RVI for 90 days prior to Enrollment, and intention to abstain from RVI for the duration of study participation.
Exclusion criteria
1. At Screening: 1. History of inflammatory bowel disease; 2. Current anorectal condition that would impede product placement or assessment of tolerability by participant report or exam. 2. Anticipated use and/or unwillingness to abstain from using non-study rectally-administered medications and products during study participation, including personal lubricants containing nonoxynol-9 (N-9). Note: The use of non-study personal lubricants and usual pre-RAI douches that do not contain N-9 is permitted during study participation. 3. Known adverse reaction to any of the components of the study products. 4. Participation in research studies involving drugs, medical devices, genital products, or vaccines within 30 days of the Enrollment Visit. 5. Participation in research studies involving rectal products (ever). 6. Per participant report, use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment. 7. In the 3 months prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is HIVpositive and either not on ART or of unknown ART use status (by self report). 8. In the month prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is of unknown HIV status and unknown PrEP/ART use status (by self-report). 9. Non-therapeutic injection drug use in the 12 months prior to Enrollment. 10. At either Screening or Enrollment, participant-reported symptoms and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection (RTI) requiring treatment per current WHO guidelines (http://www.who.int/hiv/ pub/sti/pub6/en/), or symptomatic urinary tract infection (UTI). Infections requiring treatment include: Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts, chancroid, pelvic inflammatory disease (PID), symptomatic bacterial vaginosis (BV), symptomatic vaginal candidiasis, and trichomoniasis. Note: Otherwise eligible participants with a symptomatic UTI or an STI/RTI requiring treatment per current WHO guidelines may be retested during the screening process and if treatment is completed and symptoms have resolved within the screening window the participant may be enrolled. Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is permitted since treatment is not required. 11. For individuals who can get pregnant: Pregnant or breastfeeding at either Screening or Enrollment or planning to become pregnant during study participation. 12. For individuals who can get pregnant: Last pregnancy outcome 90 days or less prior to Screening. 13. Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acceptability of Future Product Use | 14 weeks (three 4-week product use periods with 1-week washout periods between them) | Using a 10-point scale (1=Very Unlikely; 10=Very Likely), participants were asked to answer the following question about their most recently used product: Think about the positive and negative experiences you have had using the \[study product\] during the past 4-week period. If this \[study product\] was available and it provided some protection against HIV, how likely would you be to use it before receptive anal sex?. The endpoint was operationalized as binary, with scores 1 to 6 grouped as low acceptability and scores 7 to 10 as high acceptability. |
| Adherence to Placebo Products | 14 weeks (three 4-week product use periods with 1-week washout periods between them) | Percentage of participants who used each study product as instructed |
| Number of Grade 2+ Related Adverse Events | 14 weeks (three 4-week product use periods with 1-week washout periods between them) | Number of all Grade 2 or higher related adverse events (AE) reported in the study as defined by the DAIDS AE Grading Table |
Countries
Malawi, Peru, South Africa, Thailand, United States
Participant flow
Recruitment details
Recruitment took place at seven clinical research sites in four countries from April 2019 to March 2020
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants used rectal inserts, rectal douches, or rectal suppositories, each for a 4-week period, in six different sequencies (A-F) and were instructed to use their assigned study product prior to each RAI encounter during that period. | 217 |
| Total | 217 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 24.9 years STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 16 Participants |
| Race/Ethnicity, Customized Multiple Races | 33 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 6 Participants |
| Race/Ethnicity, Customized Other African Tribe | 38 Participants |
| Race/Ethnicity, Customized Thai | 30 Participants |
| Race/Ethnicity, Customized White | 66 Participants |
| Race/Ethnicity, Customized Xhosa | 5 Participants |
| Race/Ethnicity, Customized Zulu | 14 Participants |
| Region of Enrollment Malawi | 31 Participants |
| Region of Enrollment Peru | 30 Participants |
| Region of Enrollment South Africa | 30 Participants |
| Region of Enrollment Thailand | 30 Participants |
| Region of Enrollment United States | 96 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 214 Participants |
| Sex/Gender, Customized Female | 2 Participants |
| Sex/Gender, Customized Gender nonconforming/Variant | 5 Participants |
| Sex/Gender, Customized Male | 173 Participants |
| Sex/Gender, Customized Multiple Genders | 6 Participants |
| Sex/Gender, Customized Other Gender | 10 Participants |
| Sex/Gender, Customized Transgender Female | 19 Participants |
| Sex/Gender, Customized Transgender Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 210 | 0 / 209 | 0 / 210 |
| other Total, other adverse events | 48 / 210 | 45 / 209 | 48 / 210 |
| serious Total, serious adverse events | 0 / 210 | 0 / 209 | 0 / 210 |
Outcome results
Primary
Acceptability of Future Product Use
Using a 10-point scale (1=Very Unlikely; 10=Very Likely), participants were asked to answer the following question about their most recently used product: Think about the positive and negative experiences you have had using the \[study product\] during the past 4-week period. If this \[study product\] was available and it provided some protection against HIV, how likely would you be to use it before receptive anal sex?. The endpoint was operationalized as binary, with scores 1 to 6 grouped as low acceptability and scores 7 to 10 as high acceptability.
Time frame: 14 weeks (three 4-week product use periods with 1-week washout periods between them)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rectal Insert | Acceptability of Future Product Use | No | 56 Participants |
| Rectal Insert | Acceptability of Future Product Use | Yes | 143 Participants |
| Rectal Insert | Acceptability of Future Product Use | Missing | 2 Participants |
| Rectal Suppository | Acceptability of Future Product Use | No | 68 Participants |
| Rectal Suppository | Acceptability of Future Product Use | Yes | 132 Participants |
| Rectal Suppository | Acceptability of Future Product Use | Missing | 1 Participants |
| Rectal Douche | Acceptability of Future Product Use | Yes | 143 Participants |
| Rectal Douche | Acceptability of Future Product Use | Missing | 4 Participants |
| Rectal Douche | Acceptability of Future Product Use | No | 54 Participants |
Primary
Adherence to Placebo Products
Percentage of participants who used each study product as instructed
Time frame: 14 weeks (three 4-week product use periods with 1-week washout periods between them)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rectal Insert | Adherence to Placebo Products | No | 49 Participants |
| Rectal Insert | Adherence to Placebo Products | Yes | 150 Participants |
| Rectal Insert | Adherence to Placebo Products | Missing | 2 Participants |
| Rectal Suppository | Adherence to Placebo Products | No | 51 Participants |
| Rectal Suppository | Adherence to Placebo Products | Yes | 148 Participants |
| Rectal Suppository | Adherence to Placebo Products | Missing | 2 Participants |
| Rectal Douche | Adherence to Placebo Products | Yes | 165 Participants |
| Rectal Douche | Adherence to Placebo Products | Missing | 1 Participants |
| Rectal Douche | Adherence to Placebo Products | No | 35 Participants |
Primary
Number of Grade 2+ Related Adverse Events
Number of all Grade 2 or higher related adverse events (AE) reported in the study as defined by the DAIDS AE Grading Table
Time frame: 14 weeks (three 4-week product use periods with 1-week washout periods between them)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rectal Insert | Number of Grade 2+ Related Adverse Events | 2 Adverse events |
| Rectal Suppository | Number of Grade 2+ Related Adverse Events | 0 Adverse events |
| Rectal Douche | Number of Grade 2+ Related Adverse Events | 0 Adverse events |