FEM-PrEP (Truvada®): Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women

NCT00625404 | Completed Phase 3 Results DMC

• 1 other identifier: 10015
• Study Type: interventional
• Target: 2,120
• Locations: 3 countries
• Sites: 4

Brief Summary

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse. The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo. After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.

Conditions

HIV Infections

Keywords

Aspartate Aminotransferase (AST); Alanine Aminotransferase (ALT); HIV; HIV Prevention; Oral PrEP; Truvada; women; Tenofovir; TDF; FTC; emtricitabine; hepatitis; Pre-exposure Prophylaxis (PrEP); HIV Seronegativity

Outcome Measures

Primary Outcomes (6)

• HIV Infection

  HIV Seroconversion, with time to infection refined based on PCR results obtained from stored specimens.

  Cumulative HIV infection between enrollment and 52 weeks

• Confirmed Grade 2 or Higher Serum Creatinine Toxicity

  Repeat specimens were collected to confirm chemistry toxicities. Grade 2 or higher serum creatinine toxicity was defined as ≥1.4 times the upper limit of normal

  cumulative toxicity through 52 weeks of product use and 4 weeks post product

• Frequency of Adverse Events (AEs) During and Within 4 Weeks After Study Product Administration

  The total number of adverse events in the placebo and Truvada arms during and within 4 weeks after study product administration.

  10-26 months per site

• Confirmed Grade 3 or Higher Reduction in Phosphorus

  Repeat specimens were collected to confirm chemistry toxicities. Grade 3 phosphorus reduction was defined as ≤2.4mg/dL

  Through 52 weeks on product and 4 weeks post-product

• Confirmed Grade 3 or Higher ALT Elevation

  Grade 3 or higher ALT elevation was defined as ≥ 2.6 times the upper limit of normal

  Through 52 weeks on product and 4 weeks post-product

• Confirmed Grade 3 or Higher AST Elevation

  Grade 3 or higher AST elevation was defined as ≥ 2.6 times the upper limit of normal

  Through 52 weeks on product and 4 weeks post-product

Secondary Outcomes (6)

• Plasma HIV RNA Level (HIV-1 Viral Load)

  up to 16 weeks

• CD4+ T-cell Count

  Up to 16 weeks

• FTC and/or Tenofovir Resistance

  up to 52 weeks

• Pregnancy Complications

  up to 60 weeks

• Pill Counts and Participant Report of Adherence to Once-daily Pill Taking

  Up to 52 weeks

Study Arms (2)

Truvada Arm

EXPERIMENTAL

Daily single oral tablet of Truvada (TDF/FTC), a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).

Drug: Truvada

Placebo Arm

PLACEBO COMPARATOR

Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.

Other: Placebo

Interventions

Truvada DRUG

Daily single oral tablet of Truvada - a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).

Also known as: TDF/FTC - emtricitabine and tenofovir disoproxil fumarate

Truvada Arm

Placebo OTHER

Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
• Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
• Between 18-35 years old, inclusive
• At higher risk of becoming HIV infected
• Have a final negative result according to the site-specific screening HIV testing algorithm and a final negative result at enrollment according to the study HIV testing algorithm
• Willing to participate in all aspects of the study and to comply with study procedures, for up to 60 weeks, including:
• Be randomized
• Use study product as directed
• Adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person)
• Use a study-approved effective non-barrier method of contraception for the duration of the study
• Take study product, as evidenced by swallowing a vitamin tablet that is similar in size to the study product at enrollment
• Provide contact information and agrees to some form of contact method throughout the study
• Not intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area ( \> 1 month at a time)
• In general good health and have no condition (social or medical) which, in the opinion of the Site Investigator, would make study participation unsafe or complicate data interpretation
• Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation

Sponsors & Collaborators

• FHI 360: lead

Study Sites (4)

Bondo Clinic, Bondo District Hospital

Bondo, Nyanza, Kenya

Location

Setshaba Research Centre

Pretoria, Gauteng, South Africa

Location

Josha Research Center

Bloemfontein, South Africa

Location

Arusha Clinic, Levolosi Health Center

Arusha, Tanzania

Location

Related Publications (5)

• Lut Van Damme, M.D., Amy Corneli, Ph.D. and Douglas Taylor, Ph.D. New England Journal of Medicine 367: 411-422, 2012

  RESULT

• Mandala J, Nanda K, Wang M, De Baetselier I, Deese J, Lombaard J, Owino F, Malahleha M, Manongi R, Taylor D, Van Damme L. Liver and renal safety of tenofovir disoproxil fumarate in combination with emtricitabine among African women in a pre-exposure prophylaxis trial. BMC Pharmacol Toxicol. 2014 Dec 24;15:77. doi: 10.1186/2050-6511-15-77.

  PMID: 25539648 DERIVED

• Grant RM, Liegler T, Defechereux P, Kashuba AD, Taylor D, Abdel-Mohsen M, Deese J, Fransen K, De Baetselier I, Crucitti T, Bentley G, Agingu W, Ahmed K, Damme LV. Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. AIDS. 2015 Jan 28;29(3):331-7. doi: 10.1097/QAD.0000000000000556.

  PMID: 25503265 DERIVED

• Todd CS, Deese J, Wang M, Hubacher D, Steiner MJ, Otunga S, Van Damme L; FEM-PrEP Study Group. Sino-implant (II)(R) continuation and effect of concomitant tenofovir disoproxil fumarate-emtricitabine use on plasma levonorgestrel concentrations among women in Bondo, Kenya. Contraception. 2015 Mar;91(3):248-52. doi: 10.1016/j.contraception.2014.10.008. Epub 2014 Oct 22.

  PMID: 25459097 DERIVED

• Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, Malahleha M, Owino F, Manongi R, Onyango J, Temu L, Monedi MC, Mak'Oketch P, Makanda M, Reblin I, Makatu SE, Saylor L, Kiernan H, Kirkendale S, Wong C, Grant R, Kashuba A, Nanda K, Mandala J, Fransen K, Deese J, Crucitti T, Mastro TD, Taylor D; FEM-PrEP Study Group. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012 Aug 2;367(5):411-22. doi: 10.1056/NEJMoa1202614. Epub 2012 Jul 11.

  PMID: 22784040 DERIVED

Related Links

• Genetics Home Reference for complement factor I deficiency
• MedlinePlus: AIDS
• MedlinePlus: Hepatitis
• Drug Information: n-Octadecanoic acid
• Drug Information: Calcium stearate
• Drug Information : Aluminum monostearate
• U.S. FDA Resources

MeSH Terms

Conditions

HIV Infections; Hepatitis

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Jennifer Deese, Principal Investigator
• Organization: FHI 360

jdeese@fhi360.org

919-544-7040

Study Officials

• Lut Van Damme, MD, MS, PhD

  FHI 360

  PRINCIPAL INVESTIGATOR

• Amy Corneli, PhD, MPH

  FHI 360

  PRINCIPAL INVESTIGATOR

• Jennifer Deese, MPH

  FHI 360

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2008
• First Posted: February 28, 2008
• Study Start: May 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: January 1, 2013
• Last Updated: July 26, 2018
• Results First Posted: April 16, 2014

Record last verified: 2018-06

Locations

KE (1); ZA (2); TA (1)