AVX754 (a New Nucleoside Reverse Transcriptase Inhibitor [NRTI]) to Treat Drug-resistant HIV

Study Overview
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Brief Summary
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The study will measure how safe and effective AVX754 (a new drug for the treatment of HIV) is in treating HIV-1 infected people who have failed treatment with lamivudine.

Detailed Description
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Lamivudine or emtricitabine are commonly used in combination with other drugs for first-line treatment of HIV infection. Although effective initially, many people later on develop resistance to some or all of the drugs (including lamivudine) leading to virological failure. Resistance is associated with characteristic mutations, which for lamivudine is the M184V mutation. A change to new, active drugs must take place when patients fail their current regime, to regain control of the virus. Although there are other types of drugs available for second line treatment, there is currently no fully active, well tolerated cytidine analogue that can replace lamivudine in a second-line regimen when patients fail first line treatment. This study will measure the efficacy and safety of AVX754 (a novel cytidine analogue with activity against HIV resistant to other nucleosides) as part of a new regimen to treat patients who have failed treatment containing lamivudine, compared to the best alternative new regimen which continues to include lamivudine.

Official Title
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A Phase II, Randomised, Double-blind, Dose-ranging Study of AVX754 Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V Mutation in Reverse Transcriptase

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: AVX754
* Drug: 3TC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected M184V mutation in reverse transcriptase Currently taking lamivudine Viral load >2000 copies/ml Exclusion Criteria: Hepatitis B surface antigen positive Pregnant or breastfeeding females Hepatitis C RNA positive and requiring treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600mg BID ATC<br>600mg BID ATC | Drug: AVX754<br>* apricitabine, 600mg BID or 800mg BID<br>* Other names: apricitabine;|
| Experimental: 800mg BID ATC<br>800mg BID ATC | Drug: AVX754<br>* apricitabine, 600mg BID or 800mg BID<br>* Other names: apricitabine;|
| Active Comparator: 150mg BID 3TC<br>150mg BID 3TC | Drug: 3TC<br>* 3TC, 150mg BID<br>* Other names: lamivudine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HIV RNA levels at day 21 |  | day 21 | 
| Time-weighted average change from baseline in HIV RNA levels through 21 days |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HIV RNA levels at days 7, 14, 21 |  | days 7, 14, 21 | 
| Proportion of subjects with HIV RNA levels <400 or <50 at days 7, 14, 21, and weeks 24 and 48 |  | days 7, 14, 21, and weeks 24 and 48 | 
| Change from baseline and change in ratio of CD4+ and CD8+ cells at day 21 and weeks 24 and 48 |  | day 21 and weeks 24 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Immunodeficiency Virus, anti-retroviral therapy, nucleoside analogue, reverse transcriptase, lamivudine, resistance mutation, Treatment Experienced