Test Albuvirtide in Experienced Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of albuvirtide combined with lopinavir-ritonavir (LPV/r) in HIV-1-infected patients who failed first-line antiretroviral therapy (ART).

Detailed Description
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This was a 48-week, multi-center, open-label, randomized and controlled, non-inferiority phase 3 clinical trial to evaluate the safety and efficacy of albuvirtide combined with LPV/r in HIV-1 infected patients who failed their first-line ART and had HIV-1 RNA levels ≥ 1000 copies/mL at screening. The trial was conducted in 12 sites in China. Subjects meeting inclusion criteria were randomized in a 1:1 ratio to ABT group and NRTI group, in which the ABT group received albuvirtide and LPV/r combination therapy, and NRTI group received the standard 3-drug regimen of LPV/r + Lamivudine (3TC) + Tenofovir (TDF). If TDF was used in the previous regimen or genotypic resistance histories showed primary mutation to TDF, zidovudine (AZT) or abacavir (ABC) would be used. Albuvirtide was given by weekly intravenous infusion and LPV/r was given twice daily orally. A total of 418 subjects were randomized, of whom 401 received at least one treatment.

Official Title
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Efficacy and Safety of Albuvirtide for Injection Combined With LPV/r for Treatment of HIV-1-Infected Patients Failed First-line Antiretroviral Therapy

Conditions
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HIV Infections, AIDS

Intervention / Treatment
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* Drug: albuvirtide
* Drug: lopinavir-ritonavir
* Drug: tenofovir
* Drug: lamivudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16-60 years old, male or female. Those who meet the Diagnostic Criteria of AIDS and HIV Infection, the Health Industry Standard of the People's Republic of China (WS 293-2008). Those who have been undergoing antiretroviral treatment with nucleosides and non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) for at least 6 months. HIV-RNA ≥ 1000 copies/mL. Those who have no serious hepatic or renal functional impairment and other parameters are generally in the normal ranges according to the comprehensive physical examinations (including general physical examination, routine blood and urine tests, blood chemistry tests, ECG, etc.). The subjects should have a full understanding of the objective, nature, methods of the trial and the possible reactions. He/She should participate in the trial voluntarily and should sign the informed consent form. Exclusion Criteria: Those who are in an acute stage of infection, or have suffered from AIDS-related diseases (e.g. opportunistic infections or malignant tumors, etc.) at enrollment; or have suffered from opportunistic infections within 3 months prior to enrollment and the conditions have not reached a stable state within 2 weeks prior to enrollment. Those who have used protease inhibitors or HIV fusion inhibitors for antiretroviral treatment, and who have participated in HIV vaccine clinical trials or have participated in other drug trials within recent 3 months. Those who have been co-administered antiviral treatment for hepatitis. Those whose screening test results meet one of the following: hemoglobin < 9 g/dL, WBC count <2×109/L, neutrophil count < 1×109/L, PLT count < 75×109/L, transaminase > 3×ULN, total bilirubin > 2×ULN, creatinine > 1×ULN, serum creatine phosphokinase > 2×ULN. Those with allergic constitution or known allergic to ingredients of the investigational drug or ART drugs prescribed in the protocol. Currently suffering from serious chronic diseases, metabolic diseases (such as diabetes mellitus), neurological and psychiatric disorders. Patients with hemophilia A or B. Those with suspected or confirmed history of alcohol or drug abuse. Pregnant or lactating women; or women of childbearing age who refuse to take contraceptive measures during the trial. Those for whom the possibility of being enrolled is low according to the judgment of the investigator (e.g. weak physical condition, poor compliance, etc.).

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: albuvirtide, lopinavir-ritonavir<br>albuvirtide once a week and lopinavir-ritonavir twice daily for 48 weeks | Drug: albuvirtide<br>* albuvirtide 320mg administered intravenously once a week<br>* Other names: ABT;Drug: lopinavir-ritonavir<br>* lopinavir-ritonavir 400/100mg administered orally twice daily<br>* Other names: LPV/r;|
| Active Comparator: lopinavir-ritonavir,tenofovir,lamivudine<br>lopinavir-ritonavir twice daily, tenofovir once daily and lamivudine once daily for 48 weeks | Drug: lopinavir-ritonavir<br>* lopinavir-ritonavir 400/100mg administered orally twice daily<br>* Other names: LPV/r;Drug: tenofovir<br>* tenofovir 300mg administered orally once daily<br>* Other names: TDF;Drug: lamivudine<br>* lamivudine 300mg administered orally once daily<br>* Other names: 3TC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants of virological suppression at Week 48 | Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 | Through Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of viral load | Changes of HIV-1 RNA relative to baseline at Week 48 | Baseline to Week 48 | 
| Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 | Through Week 48 | 
| Changes of CD4 cell count | Changes of CD4 cell count relative to baseline at Week 48 | Baseline to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, AIDS, Albuvirtide, Treatment-experienced, Fusion inhibitor