Rectal Microbicide Acceptability, Tolerability and Adherence

NCT ID: NCT03671239

Last Updated: 2023-01-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

217 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-26

Study Completion Date

2020-07-27

Brief Summary

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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

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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.

Conditions

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HIV Prevention

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Product Sequence A

Participants will use placebo rectal inserts during the first 4-week product use period, placebo rectal douches during the second 4-week product use period, and placebo rectal suppositories during the third and final 4-week product use period.

Group Type OTHER

Placebo rectal insert

Intervention Type BEHAVIORAL

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.

Placebo rectal suppository

Intervention Type BEHAVIORAL

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.

Placebo rectal douche

Intervention Type BEHAVIORAL

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.

Product Sequence B

Participants will use placebo rectal douches during the first 4-week product use period, placebo rectal suppositories during the second 4-week product use period, and placebo rectal inserts during the third and final 4-week product use period.

Group Type OTHER

Placebo rectal insert

Intervention Type BEHAVIORAL

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.

Placebo rectal suppository

Intervention Type BEHAVIORAL

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.

Placebo rectal douche

Intervention Type BEHAVIORAL

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.

Product Sequence C

Participants will use rectal suppositories during the first 4-week product use period, rectal inserts during the second 4-week product use period, and rectal douches during the third and final 4-week product use period.

Group Type OTHER

Placebo rectal insert

Intervention Type BEHAVIORAL

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.

Placebo rectal suppository

Intervention Type BEHAVIORAL

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.

Placebo rectal douche

Intervention Type BEHAVIORAL

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.

Product Sequence D

Participants will use placebo rectal inserts during the first 4-week product use period, placebo rectal suppositories during the second 4-week product use period, and placebo rectal douches during the third and final 4-week product use period.

Group Type OTHER

Placebo rectal insert

Intervention Type BEHAVIORAL

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.

Placebo rectal suppository

Intervention Type BEHAVIORAL

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.

Placebo rectal douche

Intervention Type BEHAVIORAL

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.

Product Sequence E

Participants will use placebo rectal douches during the first 4-week product use period, placebo rectal inserts during the second 4-week product use period, and placebo rectal suppositories during the third and final 4-week product use period.

Group Type OTHER

Placebo rectal insert

Intervention Type BEHAVIORAL

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.

Placebo rectal suppository

Intervention Type BEHAVIORAL

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.

Placebo rectal douche

Intervention Type BEHAVIORAL

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.

Product Sequence F

Participants will use placebo rectal suppositories during the first 4-week product use period, placebo rectal douches during the second 4-week product use period, and placebo rectal inserts during the third and final 4-week product use period.

Group Type OTHER

Placebo rectal insert

Intervention Type BEHAVIORAL

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.

Placebo rectal suppository

Intervention Type BEHAVIORAL

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.

Placebo rectal douche

Intervention Type BEHAVIORAL

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.

Interventions

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Placebo 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.

Intervention Type BEHAVIORAL

Placebo 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.

Intervention Type BEHAVIORAL

Placebo 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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Microbicide Trials Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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José A Bauermeister, PhD, MPH

Role: STUDY_CHAIR

University of Pennsylvania

Locations

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Alabama Clinical Research Site

Birmingham, Alabama, United States

Site Status

Bridge HIV Clinical Research Site

San Francisco, California, United States

Site Status

University of Pittsburgh Clinical Research Site

Pittsburgh, Pennsylvania, United States

Site Status

Blantyre Clinical Research Site

Blantyre, , Malawi

Site Status

San Miguel Clinical Research Site

San Miguel, , Peru

Site Status

Wits Reproductive Health and HIV Institute Clinical Research Site

Johannesburg, , South Africa

Site Status

Chiang Mai University HIV Prevention Clinical Research Site

Chiang Mai, , Thailand

Site Status

Countries

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United States Malawi Peru South Africa Thailand

References

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Bauermeister J, Tingler R, Liu A, Chariyalertsak S, Hoesley C, Gonzales P, et al. Acceptability and choice for three placebo products used with receptive anal sex. Conference on Retroviruses and Opportunistic Infections (CROI), Mar 6-10, 2021; Abstract # 716

Reference Type BACKGROUND

Bauermeister J, Lin W, Tingler R, Liu A, Chariyalertsak S, Hoesley C, Gonzales P, Ho K, Kayange N, Phillips TP, Johnson S, Brown E, Zemanek J, Jacobson CE, Doncel GF, Piper J; MTN-035 Protocol Team for the Microbicide Trials Network. A conjoint experiment of three placebo rectal products used with receptive anal sex: results from MTN-035. J Int AIDS Soc. 2024 Mar;27(3):e26219. doi: 10.1002/jia2.26219.

Reference Type DERIVED
PMID: 38494656 (View on PubMed)

Choi SK, Bauermeister J, Tingler RC, Johnson S, Macagna N, Ho K, Hoesley C, Liu A, Kayange N, Palanee-Phillips T, Chariyalertsak S, Gonzales P, Piper JM; MTN-035 Protocol Team. A latent trajectory analysis of young sexual and gender minorities' adherence to three rectal microbicide placebo formulations (MTN-035; a randomized crossover trial). BMC Public Health. 2023 Dec 8;23(1):2464. doi: 10.1186/s12889-023-17368-y.

Reference Type DERIVED
PMID: 38066471 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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Other Identifiers

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UM1AI068633

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1AI068615

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1AI106707

Identifier Type: NIH

Identifier Source: secondary_id

View Link

38459

Identifier Type: OTHER

Identifier Source: secondary_id

MTN-035

Identifier Type: -

Identifier Source: org_study_id

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