BufferGel and PRO 2000/5: Vaginal Gels to Prevent HIV Infection in Women

HIV Infections Clinical Trial

Official title:

Phase II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel (P) for the Prevention of HIV Infection in Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00074425
• Other study ID #: HPTN 035
• Secondary ID: 10065
• Status: Completed
• Phase: Phase 2
• Start date: January 2005
• Est. completion date: September 2008

Study information

• Verified date: July 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The majority of HIV infected people worldwide became infected with the virus through heterosexual contact. BufferGel and PRO 2000 Gel are vaginal gels designed to prevent women from becoming infected with HIV during sexual intercourse with an HIV infected partner. This study will test the safety and effectiveness of these gels.

Description:

Accessible, usable, and effective vaginal microbicides could significantly decrease the spread of HIV. Vaginal microbicides could be used with condoms to prevent HIV infection; they could also be used in situations in which an individual is unable to negotiate condom use. Vaginal microbicides are potentially bidirectional, preventing both male-to-female and female-to-male HIV transmission. This study will evaluate the safety and effectiveness of two vaginal microbicides, BufferGel and PRO 2000/5, in preventing the transmission of HIV. The study will also evaluate the effectiveness of these gels in preventing other common sexually transmitted infections (STIs).

BufferGel is a buffering agent designed to maintain normal vaginal acidity in the presence of ejaculate. Studies have shown that HIV is inactivated below a pH of 4 to 5.8. Carbopol 974, the major nonaqueous component of BufferGel, is commonly used as a gelling or tableting agent and has a well-documented safety record. BufferGel has proven safe and well tolerated in Phase I studies. PRO 2000/5 inhibits viral entry into susceptible cells. PRO 2000/5 has also been evaluated in Phase I studies and was found to be safe and well tolerated.

Participants in this study will be randomly assigned to receive one of four interventions:

BufferGel, PRO 2000/5, placebo gel, or no gel. All participants will receive HIV risk reduction counseling, condoms, and diagnosis and treatment of sexually transmitted diseases. Participants in the three gel arms will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of the product (BufferGel, PRO 2000/5, or placebo gel) intravaginally up to 60 minutes before each vaginal intercourse while in the study.

Participants will be enrolled for approximately 12 to 30 months, depending on when they enter the study. Participants will have two screening study visits and then monthly visits. Monthly study visits may take place at a clinic, the participant's home, or other community site. Monthly visits will include a medical interview; urine testing, including pregnancy testing; HIV and sexually transmitted infection risk reduction counseling; and distribution of study supplies (condoms and gel-filled applicators). Blood collection will occur at selected monthly visits. Four times a year, participants will be seen in the clinic for a more structured medical interview, pelvic exam, and HIV testing. At one of these visits, participants at particular sites who are willing will be asked to complete a behavioral risk assessment. At some visits vaginal fluid swabs will occur. Participants at non-US study sites will be asked for permission for these swabs to be stored for further testing. Assessment interviews will be both face to face and self-reporting.

Other known NCT identifiers

• NCT00197665

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3101
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Note: Per the 12/15/06 amendment, all study participants will now enter the Phase IIb study.

Inclusion Criteria:

• HIV uninfected

• Have had sexual intercourse at least once in the 3 months prior to study entry

• Able to provide adequate contact information to study officials for purposes of follow-up

Exclusion Criteria:

• History of adverse reaction to latex

• Nonmedical injection drug use in the 12 months prior to study entry

• Vaginal intercourse more than an average of two times per day in the 2 weeks prior to study entry

• Plan to become pregnant in the 30 months after study entry

• Plan to travel away from the study site for more than 3 consecutive months in the 30 months after study entry

• Plan to relocate away from the study site in the 30 months after study entry

• Participation in another clinical trial of a vaginal product

• Pregnant within 42 days of study entry

• Have a sexually transmitted disease or other reproductive tract infection diagnosed by study staff

• Abnormal pelvic exam indicating deep epithelial disruption

• Condition that, in the opinion of the investigator, may interfere with the study

• Liver or kidney function abnormality of Grade 3 or higher

• Blood or blood clotting abnormality of Grade 4 or higher

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections

Intervention

Drug:
• BufferGel
Participants will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of BufferGel intravaginally up to 60 minutes before each vaginal intercourse while in the study.
• PRO 2000/5 Gel
Participants will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of PRO 2000/5 Gel intravaginally up to 60 minutes before each vaginal intercourse while in the study.
• Placebo gel
Participants will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of PRO 2000/5 Gel intravaginally up to 60 minutes before each vaginal intercourse while in the study.

Locations

Country	Name	City	State
Malawi	College of Med. JHU CRS	Blantyre	Southern
Malawi	University of North Carolina Lilongwe CRS	Lilongwe	Central
South Africa	Chatsworth CRS	Chatsworth	KwaZulu-Natal
South Africa	Med. Research Council-Hlabisa	Durban	KwaZulu-Natal
United States	3535 Market Street CRS	Philadelphia	Pennsylvania
Zambia	Kamwala Clinic CRS	Lusaka
Zimbabwe	Seke South CRS	Chitungwiza
Zimbabwe	Spilhaus CRS	Harare

Sponsors (5)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), HIV Prevention Trials Network, National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA)

Countries where clinical trial is conducted

United States,  Zambia,  Zimbabwe,  Malawi,  South Africa, 

References & Publications (9)

Abdool Karim SS, Richardson BA, Ramjee G, Hoffman IF, Chirenje ZM, Taha T, Kapina M, Maslankowski L, Coletti A, Profy A, Moench TR, Piwowar-Manning E, Mâsse B, Hillier SL, Soto-Torres L; HIV Prevention Trials Network (HPTN) 035 Study Team. Safety and effe — View Citation

Clarke JG, Peipert JF, Hillier SL, Heber W, Boardman L, Moench TR, Mayer K. Microflora changes with the use of a vaginal microbicide. Sex Transm Dis. 2002 May;29(5):288-93. — View Citation

D'Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des. 2004;10(3):315-36. Review. — View Citation

MacQueen KM, Namey E, Chilongozi DA, Mtweve SP, Mlingo M, Morar N, Reid C, Ristow A, Sahay S; HPTN 035 Standard of Care Assessment Team. Community perspectives on care options for HIV prevention trial participants. AIDS Care. 2007 Apr;19(4):554-60. — View Citation

Mayer KH, Karim SA, Kelly C, Maslankowski L, Rees H, Profy AT, Day J, Welch J, Rosenberg Z; HIV Prevention Trials Network (HPTN) 020 Protocol Team. Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS. 2003 Feb 14;17(3):321-9. — View Citation

Mayer KH, Peipert J, Fleming T, Fullem A, Moench T, Cu-Uvin S, Bentley M, Chesney M, Rosenberg Z. Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. Clin Infect Dis. 2001 Feb 1;32(3):476-82. Epub 2001 Jan 26. — View Citation

Minces LR, McGowan I. Advances in the Development of Microbicides for the Prevention of HIV Infection. Curr Infect Dis Rep. 2010 Jan;12(1):56-62. doi: 10.1007/s11908-009-0076-5. — View Citation

Tabet SR, Callahan MM, Mauck CK, Gai F, Coletti AS, Profy AT, Moench TR, Soto-Torres LE, Poindexter III AN, Frezieres RG, Walsh TL, Kelly CW, Richardson BA, Van Damme L, Celum CL. Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men. J Acquir Immune Defic Syndr. 2003 Aug 1;33(4):476-83. Erratum in: J Acquir Immune Defic Syndr. 2003 Sep 1;34(1):118. — View Citation

van De Wijgert J, Fullem A, Kelly C, Mehendale S, Rugpao S, Kumwenda N, Chirenje Z, Joshi S, Taha T, Padian N, Bollinger R, Nelson K. Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites. J Acquir Immune Defic Syndr. 2001 Jan 1;26(1):21-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of BufferGel and 0.5% PRO 2000/5 Gel (P), as assessed by deep epithelial disruption, other genital symptoms, or other systemic symptoms		Throughout study
Primary	HIV infection as measured by seroconversion		Throughout study
Secondary	Bacterial vaginosis		Throughout study
Secondary	Chlamydia infection		Throughout study
Secondary	Genital ulcer disease		Throughout study
Secondary	Gonorrhea infection		Throughout study
Secondary	Herpes simplex virus-2 infection		Throughout study
Secondary	Pregnancy		Throughout study
Secondary	Syphilis infection		Throughout study
Secondary	Trichomoniasis		Throughout study
Secondary	Acceptability of study product		At Month 3 and study exit
Secondary	Number of behavioral risk assessment questions not answered in self-reported interviews		Throughout study
Secondary	Rates of condom use versus gel use		Throughout study
Secondary	Establishment of a repository of vaginal swab specimens for long-term storage and future research testing on biomarkers of microbicide safety and effectiveness		Throughout study

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