Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection

Study Overview
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Brief Summary
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Apricitabine is a new NRTI which is active against drug-resistant HIV. NRTIs are often included as part of patients' treatment, but many HIV-infected patients develop resistance to commonly used NRTIs such as lamivudine (3TC) and emtricitabine (FTC). This study will examine whether including apricitabine as part of patients' treatment is more effective than including lamivudine,when patients change treatment because of drug resistance.

Detailed Description
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ATC has potent antiviral activity both in vitro (against wild-type HIV-1 and HIV-1 with mutations in reverse transcriptase that confer resistance to NRTIs), and in clinical studies in both treatment-naïve and treatment-experienced patients with M184V, including in the presence of additional NRTI mutations in reverse transcriptase. The M184V mutation is most commonly present amongst patients failing regimens containing either of the two deoxycytidine analogs lamivudine and emtricitabine. Whilst lamivudine therapy is often maintained in patients harboring the M184V mutation in some settings, there are no deoxycytidine analogs currently available that effectively suppress replication of HIV-1 containing the M184V/I mutation, particularly in the presence of other additional NRTI mutations. The purpose of this study is to extend the efficacy and safety established in study AVX-201 of ATC in patients who are HIV-1 infected and have failed treatment with lamivudine or emtricitabine and have confirmed M184V/I mutation. Patients to be enrolled will be failing their current lamivudine- or emtricitabine-containing regimen and therefore have limited remaining NRTI treatment options. This study will investigate whether it is possible to improve control of HIV-1 viral replication by including ATC within a treatment experienced patient's new optimized background regimen following ART treatment failure.

Official Title
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A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: apricitabine
* Drug: lamivudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 positive with M184V/I mutation in reverse transcriptase; 18 years of age or older; Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: Female patients who are pregnant or breastfeeding; Current hepatitis B virus (HBV) infection; Current treatment for hepatitis C virus infection; Renal function not adequate

Ages Eligible for Study
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Minimum Age: 18 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: 1<br>800mg BID apricitabine plus optimised background | Drug: apricitabine<br>* 800mg BID apricitabine orally for 48 weeks<br>* Other names: AVX754;|
| Active Comparator: 2<br>150mg BID lamivudine plus optimised background | Drug: lamivudine<br>* 150mg BID lamivudine orally for 48 weeks<br>* Other names: 3TC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W24 |  | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to loss of virological response (TLOVR analysis; FDA algorithm) at W12, W24 and W48 (<50 copies/mL) |  | week 12, 24, and 48 | 
| Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W48 |  | week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, Drug resistance, Reverse transcriptase inhibitor, Nucleoside analogue, treatment experienced