Rectal Microbicide Acceptability, Tolerability and Adherence

• Sponsor: Microbicide Trials Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT03671239
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 217
• Locations: 7
• Arms: 6
• Actual Duration (Months): 15
• Patients Per Site: 31
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Prevention	Behavioral: Placebo rectal insert; Behavioral: Placebo rectal suppository; Behavioral: Placebo rectal douche	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Acceptability, Tolerability, and Adherence of Three Rectal Microbicide Placebo Formulations Among HIV Seronegative Cisgender Men, Transgender Men and Transgender Women Who Engage in Receptive Anal Intercourse
• Actual Study Start Date: Apr 26, 2019
• Actual Primary Completion Date: Jul 27, 2020
• Actual Study Completion Date: Jul 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: 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.	Behavioral: 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.; 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.; 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.
Other: 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.	Behavioral: 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.; 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.; 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.
Other: 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.	Behavioral: 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.; 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.; 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.
Other: 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.	Behavioral: 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.; 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.; 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.
Other: 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.	Behavioral: 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.; 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.; 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.
Other: 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.	Behavioral: 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.; 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.; 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.

Outcome Measures

Primary Outcome Measures

1. Likelihood of Future Product Use Scale [14 weeks (three 4-week product use periods with 1-week washout periods between them)]

   On a scale of 1 (low likelihood) to 10 (high likelihood), participant self-report of likelihood of product use if product is shown to be effective

2. Adherence to Placebo Products [14 weeks (three 4-week product use periods with 1-week washout periods between them)]

   Percentage of occasions when each study product was used as instructed

3. Frequency of Grade 2+ Adverse Events [14 weeks (three 4-week product use periods with 1-week washout periods between them)]

   Number of all Grade 2 or higher adverse events (AE) as defined by the DAIDS AE Grading Table

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts 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:

11. Hormonal methods;

12. Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions);

13. Sterilization (of participant or, if in a monogamous relationship, of partner, as defined in site SOPs);

14. 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:

2. History of inflammatory bowel disease;

3. Current anorectal condition that would impede product placement or assessment of tolerability by participant report or exam.

4. 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.

1. Known adverse reaction to any of the components of the study products.

2. Participation in research studies involving drugs, medical devices, genital products, or vaccines within 30 days of the Enrollment Visit.

3. Participation in research studies involving rectal products (ever).

4. Per participant report, use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment.

5. 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).

6. 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).

7. Non-therapeutic injection drug use in the 12 months prior to Enrollment.

8. 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.

1. For individuals who can get pregnant: Pregnant or breastfeeding at either Screening or Enrollment or planning to become pregnant during study participation.

2. For individuals who can get pregnant: Last pregnancy outcome 90 days or less prior to Screening.

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Research Site	Birmingham	Alabama	United States	35294
2	Bridge HIV Clinical Research Site	San Francisco	California	United States	94102
3	University of Pittsburgh Clinical Research Site	Pittsburgh	Pennsylvania	United States	15216
4	Blantyre Clinical Research Site	Blantyre		Malawi
5	San Miguel Clinical Research Site	San Miguel		Peru	15088
6	Wits Reproductive Health and HIV Institute Clinical Research Site	Johannesburg		South Africa	2038
7	Chiang Mai University HIV Prevention Clinical Research Site	Chiang Mai		Thailand	50202

Sponsors and Collaborators

• Microbicide Trials Network
• 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)

Investigators

• Study Chair: José A Bauermeister, PhD, MPH, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol - Jun 15, 2018
• Statistical Analysis Plan - Jan 25, 2021
• Informed Consent Form - Jun 15, 2018

More Information

Publications

None provided.

• Responsible Party: Microbicide Trials Network
• ClinicalTrials.gov Identifier: NCT03671239
• Other Study ID Numbers: MTN-035; UM1AI068633; UM1AI068615; UM1AI106707; 38459
• First Posted: Sep 14, 2018
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Microbicide Trials Network: Acceptability; Rectal microbicide

Study Results

No Results Posted as of Jun 23, 2021