Rectal Microbicide Acceptability, Tolerability and Adherence

NCT03671239 | Completed Results DMC

• 5 other identifiers: MTN-035UM1AI068633UM1AI068615UM1AI10670738459
• Study Type: interventional
• Target: 217
• Locations: 5 countries
• Sites: 7

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.

Conditions

HIV Prevention

Keywords

Acceptability; Rectal microbicide

Outcome Measures

Primary Outcomes (3)

• 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".

  14 weeks (three 4-week product use periods with 1-week washout periods between them)

• Adherence to Placebo Products

  Percentage of participants who used each study product as instructed

  14 weeks (three 4-week product use periods with 1-week washout periods between them)

• 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

  14 weeks (three 4-week product use periods with 1-week washout periods between them)

Study Arms (6)

Product Sequence A

OTHER

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.

Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche

Product Sequence B

OTHER

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.

Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche

Product Sequence C

OTHER

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.

Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche

Product Sequence D

OTHER

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.

Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche

Product Sequence E

OTHER

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.

Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche

Product Sequence F

OTHER

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.

Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche

Interventions

Placebo rectal insert 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.

Product Sequence A; Product Sequence B; Product Sequence C; Product Sequence D; Product Sequence E; Product Sequence F

Placebo rectal suppository 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.

Product Sequence A; Product Sequence B; Product Sequence C; Product Sequence D; Product Sequence E; Product Sequence F

Placebo rectal douche 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 A; Product Sequence B; Product Sequence C; Product Sequence D; Product Sequence E; Product Sequence F

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Cisgender men, transgender men (TGM) and transgender women (TGW)
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men (cis or transgender) and TGW who are 18-35 years old at Screening, verified per site SOP.
• Able and willing to provide written informed consent.
• HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results.
• Able and willing to provide adequate locator information, as defined in site SOP.
• Available to return for all study visits and willing to comply with study participation requirements.
• In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee.
• 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.
• 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).
• For individuals who can get pregnant (i.e., TGM with a female reproductive system): a negative pregnancy test at Screening and Enrollment.
• 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:
• Hormonal methods;
• Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions);
• Sterilization (of participant or, if in a monogamous relationship, of partner, as defined in site SOPs);
• Abstinence from RVI for 90 days prior to Enrollment, and intention to abstain from RVI for the duration of study participation.

You may not qualify if:

• At Screening:
• History of inflammatory bowel disease;
• Current anorectal condition that would impede product placement or assessment of tolerability by participant report or exam.
• 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.
• Known adverse reaction to any of the components of the study products.
• Participation in research studies involving drugs, medical devices, genital products, or vaccines within 30 days of the Enrollment Visit.
• Participation in research studies involving rectal products (ever).
• Per participant report, use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment.
• 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).
• 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).
• Non-therapeutic injection drug use in the 12 months prior to Enrollment.
• 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.

Sponsors & Collaborators

• Microbicide Trials Network: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (7)

Alabama Clinical Research Site

Birmingham, Alabama, 35294, United States

Location

Bridge HIV Clinical Research Site

San Francisco, California, 94102, United States

Location

University of Pittsburgh Clinical Research Site

Pittsburgh, Pennsylvania, 15216, United States

Location

Blantyre Clinical Research Site

Blantyre, Malawi

Location

San Miguel Clinical Research Site

San Miguel, 15088, Peru

Location

Wits Reproductive Health and HIV Institute Clinical Research Site

Johannesburg, 2038, South Africa

Location

Chiang Mai University HIV Prevention Clinical Research Site

Chiang Mai, 50202, Thailand

Location

Related Publications (3)

• 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

  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.

  PMID: 38494656 DERIVED

• 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.

  PMID: 38066471 DERIVED

Related Links

• Primary result abstract published by CROI

Limitations and Caveats

First, self-reported responses tend to be favorable due to social desirability. Second, we recruited a convenience sample of participants willing to use each of the study products at least once per week as required by the protocol. Third, given the placebo nature of the three products used in our trial, we were unable to employ a biological confirmation method regarding participants' product use and adherence. Finally, we were unable to recruit the sexual partners of our study participants.

Results Point of Contact

• Title: Jose A. Bauermeister, PhD
• Organization: University of Pennsylvania

bjose@nursing.upenn.edu

215-898-9993

Study Officials

• José A Bauermeister, PhD, MPH

  University of Pennsylvania

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: September 14, 2018
• Study Start: April 26, 2019
• Primary Completion: July 27, 2020
• Study Completion: July 27, 2020
• Last Updated: January 20, 2023
• Results First Posted: January 20, 2023

Record last verified: 2023-01

Locations

US (3); PE (1); MA (1); ZA (1); TH (1)