Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel

NCT ID: NCT01687218

Last Updated: 2021-06-24

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

195 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-25

Study Completion Date

2015-05-26

Brief Summary

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MTN-017 is a Phase 2, multi-site, randomized, six-sequence, two three-period, open label crossover study, examining the effects of oral Truvada and reduced glycerin 1% tenofovir gel. The study population will be sexually active, HIV-uninfected males who are 18 years of age or older, who report a history of receptive anal intercourse in the past 3 months. Each of the study product regimens offers different advantages to participants seeking an effective HIV prevention agent. How these relative advantages will compare in terms of safety, acceptability, systemic and local absorption, and adherence will be examined within this study.

Detailed Description

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Conditions

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HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Group 1

Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

Group Type ACTIVE_COMPARATOR

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Group 2

Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

Group Type ACTIVE_COMPARATOR

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Group 3

Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)

Group Type ACTIVE_COMPARATOR

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Group 4

Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

Group Type ACTIVE_COMPARATOR

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Group 5

Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

Group Type ACTIVE_COMPARATOR

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Group 6

Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks);followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)

Group Type ACTIVE_COMPARATOR

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Interventions

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Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)

Intervention Type DRUG

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or transgender female \> age of 18 at Screening
2. Able and willing to provide written informed consent
3. HIV-1 uninfected at Screening and Enrollment
4. Able and willing to provide adequate locator information, as defined in site SOP
5. Available to return for all study visits, barring unforeseen circumstances and willing to comply with study participation requirements
6. In general good health at Screening and Enrollment, as determined by the site IoR or designee
7. Per participant report, a history of consensual RAI at least once in the past 3 months
8. Per participant report at Screening and Enrollment, agrees not to engage in receptive or insertive sexual activity with another study participant for the duration of study participation.
9. Willing to use study-provided condoms for the duration of the study for penetrative intercourse
10. Willing to not take part in other research studies involving drugs, medical devices, vaccines or genital products for the duration of study participation (including the time between Screening and Enrollment)
11. Men and transgender females who agree to take part in the PK, PD and Mucosal Immunology Subset, must also agree to abstain from:

* Inserting anything into the rectum, including abstaining from RAI for 72 hours after the collection of biopsies
* Taking non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and/or other drugs that are associated with increased likelihood of bleeding following mucosal biopsy collection for 72 hours prior to and following the collection of biopsies.

Exclusion Criteria

1. At Screening, participant-reported symptoms, and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection requiring treatment per current World Health Organization (WHO) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic Chlamydia trachomatis (CT) infection, Neisseria gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts.

Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required.

In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after the screening visit will be allowed
2. History of inflammatory bowel disease as reported by participant history
3. At Screening:

* Positive for hepatitis B surface antigen
* Positive for hepatitis C antibody
* Hemoglobin \< 10.0 g/dL
* Platelet count less than 100,000/mm3
* White blood cell count \< 2,000 cells/mm3 or \> 15,000 cells/mm3
* Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL)
* Serum creatinine \> 1.3 x the site laboratory upper limit of normal (ULN)
* Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \> 2.5× the site laboratory ULN
* PK, PD and Immunological Subset only: International normalized ratio (INR) \> 1.5× the site laboratory ULN or partial thromboplastin time (PTT) \> 1.25× the site laboratory ULN
4. Known allergy to methylparaben and/or propylparaben
5. Known allergy to any of the study products.
6. Per participant report, use of the following medications and/or products within 12 weeks prior to screening, and/or anticipated use or unwillingness to abstain from use throughout study participation:

* Any investigational products
* Systemic immunomodulatory medications
* Use of Heparin, including Lovenox®
* Warfarin
* Plavix® (clopidogrel bisulfate)
* Rectally-administered medications or products, containing N-9 or corticosteroids
7. By participant report, use of post-exposure prophylaxis (PEP) for HIV exposure within the 12 weeks prior to screening or anticipated use during study participation.
8. Symptoms suggestive of acute HIV seroconversion at Screening and Enrollment
9. Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives would make the patient unsuitable for the study or unable/unwilling to comply with the study requirements. Such conditions may include, but are not limited to, colorectal abnormalities, substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological or psychiatric disease.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

CONRAD

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ross D. Cranston, MD, FRCP

Role: STUDY_CHAIR

University of Pittsburgh Medical Center (UPMC)

Javier R. Lama, MD, MPH

Role: STUDY_CHAIR

Asociacion Civil Impacta Salud y Educacion (IMPACTA)

Locations

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HIV Research Section, San Francisco - Department of Public Health

San Francisco, California, United States

Site Status

The Fenway Institute/Fenway Community Health

Boston, Massachusetts, United States

Site Status

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, United States

Site Status

Asociacion Civil Impacta Salud y Educacion (IMPACTA)

Lima, , Peru

Site Status

University of Puerto Rico Medical Sciences Campus - Maternal Infant Studies Center (CEMI)

San Juan, , Puerto Rico

Site Status

Desmond Tutu HIV Foundation

Cape Town, , South Africa

Site Status

Research Institute for Health Sciences - Chiang Mai University

Chiang Mai, , Thailand

Site Status

Thailand MOPH - US CDC Collaboration (TUC)

Nonthaburi, , Thailand

Site Status

Countries

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United States Peru Puerto Rico South Africa Thailand

References

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Cranston RD, Lama JR, Richardson BA, Carballo-Dieguez A, Kunjara Na Ayudhya RP, Liu K, Patterson KB, Leu CS, Galaska B, Jacobson CE, Parikh UM, Marzinke MA, Hendrix CW, Johnson S, Piper JM, Grossman C, Ho KS, Lucas J, Pickett J, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu AY, Mayer KH, Zorrilla C, Schwartz JL, Rooney J, McGowan I; MTN-017 Protocol Team. MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel. Clin Infect Dis. 2017 Mar 1;64(5):614-620. doi: 10.1093/cid/ciw832.

Reference Type RESULT
PMID: 27986684 (View on PubMed)

Carballo-Dieguez A, Balan IC, Brown W 3rd, Giguere R, Dolezal C, Leu CS, Marzinke MA, Hendrix CW, Piper JM, Richardson BA, Grossman C, Johnson S, Gomez K, Horn S, Kunjara Na Ayudhya RP, Patterson K, Jacobson C, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu A, Mayer KH, Zorrilla C, Lama J, McGowan I, Cranston RD. High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women. PLoS One. 2017 Jul 27;12(7):e0181607. doi: 10.1371/journal.pone.0181607. eCollection 2017.

Reference Type RESULT
PMID: 28750059 (View on PubMed)

Giguere R, Brown W III, Balan IC, Dolezal C, Ho T, Sheinfil A, Ibitoye M, Lama JR, McGowan I, Cranston RD, Carballo-Dieguez A. Are participants concerned about privacy and security when using short message service to report product adherence in a rectal microbicide trial? J Am Med Inform Assoc. 2018 Apr 1;25(4):393-400. doi: 10.1093/jamia/ocx081.

Reference Type RESULT
PMID: 29025127 (View on PubMed)

Carballo-Dieguez A, Giguere R, Dolezal C, Leu CS, Balan IC, Brown W 3rd, Rael C, Richardson BA, Piper JM, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu A, Mayer KH, Zorrilla CD, Lama JR, McGowan I, Cranston RD; MTN-017 Protocol Team. Preference of Oral Tenofovir Disoproxil Fumarate/Emtricitabine Versus Rectal Tenofovir Reduced-Glycerin 1% Gel Regimens for HIV Prevention Among Cisgender Men and Transgender Women Who Engage in Receptive Anal Intercourse with Men. AIDS Behav. 2017 Dec;21(12):3336-3345. doi: 10.1007/s10461-017-1969-1.

Reference Type RESULT
PMID: 29119473 (View on PubMed)

Giguere R, Rael CT, Sheinfil A, Balan IC, Brown W 3rd, Ho T, Dolezal C, Leu CS, Liu A, Mayer KH, Lama JR, McGowan I, Carballo-Dieguez A, Cranston RD; MTN-017 Protocol Team. Factors Supporting and Hindering Adherence to Rectal Microbicide Gel Use with Receptive Anal Intercourse in a Phase 2 Trial. AIDS Behav. 2018 Feb;22(2):388-401. doi: 10.1007/s10461-017-1890-7.

Reference Type RESULT
PMID: 28825142 (View on PubMed)

Brown W 3rd, Giguere R, Sheinfil A, Ibitoye M, Balan I, Ho T, Brown B, Quispe L, Sukwicha W, Lama JR, Carballo-Dieguez A, Cranston RD. Challenges and solutions implementing an SMS text message-based survey CASI and adherence reminders in an international biomedical HIV PrEP study (MTN 017). J Biomed Inform. 2018 Apr;80:78-86. doi: 10.1016/j.jbi.2018.02.018. Epub 2018 Mar 6.

Reference Type RESULT
PMID: 29501908 (View on PubMed)

Cranston RD, Carballo-Dieguez A, Gundacker H, Richardson BA, Giguere R, Dolezal C, Siegel A, KunjaraNaAyudhya RP, Gomez K, Piper JM, Lama JR, McGowan I; MTN-017 Protocol Team. Prevalence and determinants of anal human papillomavirus infection in men who have sex with men and transgender women. Int J STD AIDS. 2019 Feb;30(2):154-162. doi: 10.1177/0956462418797864. Epub 2018 Oct 18.

Reference Type RESULT
PMID: 30336747 (View on PubMed)

Leu CS, Giguere R, Bauermeister JA, Dolezal C, Brown W 3rd, Balan IC, Richardson BA, Piper JM, Lama JR, Cranston RD, Carballo-Dieguez A. Trajectory of use over time of an oral tablet and a rectal gel for HIV prevention among transgender women and men who have sex with men. AIDS Care. 2019 Mar;31(3):379-387. doi: 10.1080/09540121.2018.1533223. Epub 2018 Oct 14.

Reference Type RESULT
PMID: 30318905 (View on PubMed)

Liu AY, Norwood A, Gundacker H, Carballo-Dieguez A, Johnson S, Patterson K, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Mayer KH, Zorrilla C, Buchbinder S, Piper JM, Lama JR, Cranston RD. Brief Report: Routine Use of Oral PrEP in a Phase 2 Rectal Microbicide Study of Tenofovir Reduced-Glycerin 1% Gel (MTN-017). J Acquir Immune Defic Syndr. 2019 Aug 15;81(5):516-520. doi: 10.1097/QAI.0000000000002066.

Reference Type RESULT
PMID: 31299013 (View on PubMed)

Balan IC, Giguere R, Brown W 3rd, Carballo-Dieguez A, Horn S, Hendrix CW, Marzinke MA, Ayudhya RPKN, Patterson K, Piper JM, McGowan I, Lama JR, Cranston RD; MTN-017 Protocol Team. Brief Participant-Centered Convergence Interviews Integrate Self-Reports, Product Returns, and Pharmacokinetic Results to Improve Adherence Measurement in MTN-017. AIDS Behav. 2018 Mar;22(3):986-995. doi: 10.1007/s10461-017-1955-7.

Reference Type RESULT
PMID: 29076032 (View on PubMed)

McGowan IM, Kunjara Na Ayudhya RP, Brand RM, Marzinke MA, Hendrix CW, Johnson S, Piper J, Holtz TH, Curlin ME, Chitwarakorn A, Raengsakulrach B, Doncel G, Schwartz JL, Rooney JF, Cranston RD. An Open-Label Pharmacokinetic and Pharmacodynamic Assessment of Tenofovir Gel and Oral Emtricitabine/Tenofovir Disoproxil Fumarate. AIDS Res Hum Retroviruses. 2022 Apr;38(4):279-287. doi: 10.1089/AID.2021.0115. Epub 2021 Oct 29.

Reference Type DERIVED
PMID: 34541872 (View on PubMed)

Other Identifiers

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5UM1AI068633

Identifier Type: NIH

Identifier Source: secondary_id

View Link

11857

Identifier Type: OTHER

Identifier Source: secondary_id

MTN-017

Identifier Type: -

Identifier Source: org_study_id

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