First Study to Evaluate the Capacity of Maraviroc Drug to Protect Against HIV Infection in Samples of Rectal Mucosa From Healthy Volunteers

PILOT STUDY OF PROTECTION AGAINST ex Vivo HIV INFECTION IN RECTAL MUCOSA IN HEALTHY VOLUNTEERS AFTER ADMINISTRATION OF MARAVIROC

Pre-exposure prophylaxis (PrEP) is a method of preventing HIV infection through the use of antiretroviral (ARV) medications before exposure to HIV. This study will assess the potential of MVC as a "on demand" pre-exposure prophylaxis, within a strategy for the prevention of HIV infection in men who have sex with men (MSM).

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Maraviroc; Drug: Maraviroc; Drug: TVD 300/200 QD

Detailed Description

Several clinical trials are currently under way evaluating the safety and effectiveness of ARV-based PrEP for preventing HIV infection. The results of the first efficacy trials of ARV-based PrEP showed fewer HIV infections among study participants receiving the study drugs compared to those receiving placebo. Although the results are promising, concerns about adherence, pharmacokinetics, and toxicity still needs further exploration so new and more effective preventive pharmacological approaches should be evaluated. This trial will evaluate the safety, pharmacokinetics and efficacy of ex vivo HIV infection of rectal mucosa by the CCR5 antagonist drug maraviroc (Selzentry) administered to healthy volunteers. This trial will last approximately one year. Twenty-one volunteers will receive MVC 300 mg orally in a single dose. Study visits will occur at enrollment and at days 0, 7, 9, 14 and 16. All study visits will include a physical examination, blood collection and storage and in the basal visit and a day 7 or 9 the participants will undergo a colonoscopy. Ex vivo HIV infectivity in rectal mucosa biopsies and plasma/mucosa MVC levels will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias i Pujol Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Men who have sex with men (MSM)
2. Age 18 years or above
3. HIV negative at the time of inclusion 4. Signed informed consent

Exclusion Criteria:

1. Existence of sexually transmitted infection (STI) or active systemic infection
2. Submit a contraindication to rectal biopsy
3. Take any drugs concomitantly with interactions with the MVC
4. Subject unable to follow protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MVC 300 mg; MVC 300 mg in unique dose	Drug: Maraviroc; Unique dose of Maraviroc 300mg; Drug: Maraviroc; Unique dose of Maraviroc 600mg
Active Comparator: TVD 300/200 QD; TVD 300/200 QD during 7 days.	Drug: TVD 300/200 QD; TVD 300/200 QD during 7 days
Experimental: Maraviroc 600mg; MVC 600mg in unique dose	Drug: Maraviroc; Unique dose of Maraviroc 300mg; Drug: Maraviroc; Unique dose of Maraviroc 600mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infectivity of HIV: p24 production	HIV replication will be measured by the determination of HIV p24 production in culture supernatant after 12 days of culture. The HIV production in ex vivo cultures from the basal and after drug administration will be compared and the results will be expressed as a measure of Maraviroc efficacy.	Baseline
Infectivity of HIV: p24 production	HIV replication will be measured by the determination of HIV p24 production in culture supernatant after 12 days of culture. The HIV production in ex vivo cultures from the basal and after drug administration will be compared and the results will be expressed as a measure of Maraviroc efficacy.	Visit 1 (Group 1: day 8, Group 2: day 7, Grop 3: day 9)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maraviroc plasmatic levels	Visit 1 (Group 1: day 8, Group 2: day 7, Grop 3: day 9)
Maraviroc levels in rectal mucosa	Visit 1 (Group 1: day 8, Group 2: day 7, Grop 3: day 9)
Truvada plasmatic levels	Visit 1 (day 7)
Truvada levels in rectal mucosa	Visit 1 (day 7)

Collaborators and Investigators

• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: October 10, 2012
• First Submitted That Met QC Criteria: October 30, 2012
• First Posted (Estimate): November 1, 2012

Study Record Updates

• Last Update Posted (Estimate): March 5, 2015
• Last Update Submitted That Met QC Criteria: March 4, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: HIV, Maraviroc, PrEP, Ex vivo infection, rectal mucosa.
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: MARAVIPREX