Efficacy, Safety and Optimal Dose of VM-1500 in Comparison to Efavirenz Added to Standard-of-care Antiretroviral Therapy
- Conditions
- HIV-1-infection
- Interventions
- Registration Number
- NCT02489461
- Lead Sponsor
- Viriom
- Brief Summary
The study is conducted in two stages and open-label stage of the study.
At the first stage of the study, the main purpose was to choose the optimal dose of VM-1500 (20 mg or 40 mg per day) in addition to standard-of-care basic antiretroviral therapy consisting of two NRTIs, in terms of reduction of viral load at Week 12 (\<400 copies/ml) in treatment-naïve HIV-1-infected patients.
At the second stage of the study, the main purpose was to evaluate efficacy of VM- 1500 (in the optimal dose selected at the first stage of the study) in comparison to Efavirenz added to standard-of-care antiretroviral therapy of two NRTIs, in terms of reduction of viral load at Week 24 to the undetectable level (\<50 copies/ml) in treatment-naïve HIV-1 infected patients.
Open-label stage of the study continued evaluation of viral load and immunological and safety parameters in HIV-1 patients receiving VM-1500 up to Week 96 and additional PK up to Week 100.
- Detailed Description
This project is an international, multicenter, randomized, partially blind clinical study to evaluate efficacy and safety of two different doses of VM-1500 in comparison with Efavirenz added to standard antiretroviral therapy including two NRTIs in treatment-naïve HIV-1-infected patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 150
- Signed Patient Information and Informed Consent Form.
- Males and females, age ≥ 18 years.
- HIV-1 infection, confirmed serologically in IFA or immunoblot analysis (or documented HIV-1 infection).
- Clinically stable HIV infection (clinical stages 1 or 2 according to the WHO classification).
- Indications (in the Investigator's opinion) for ART, according to the WHO Summary Guideline for use of antiretroviral drugs in HIV prevention and treatment (2013).
- HIV-1 RNA plasma level ≥ 5 000 copies/ml at screening.
- СD4+ Т-cells number > 200 cells/mm3 at screening.
- Laboratory parameters as follows:
White blood cells ≥ 2900/mm3 (2,9 x 109 cells/l) Absolute neutrophils ≥ 1500/mm3 (1,5 x 109 cells/l) Platelets ≥ 100000/mm3 (100 x 109 cells/l) Hemoglobin ≥ 9.0 g/dl Total bilirubin ≤ 1.5 x ULN AST and ALT≤ 2.5 x ULN Renal function GFR > 60 ml/min
- Primary HIV-1 resistance to ART. Viral resistance mutations are defined as any basic mutations of resistance to NNRTIs, according to the updated list of VIH-1 resistance mutations (International AIDS society, 2013), associated with drug resistance in any genotype.
- History of antiretroviral therapy (ART), including for the prevention of vertical transmission of HIV.
- Acute hepatitis or hepatic cirrhosis of any etiology; anti-HCV antibodies or HBsAg at screening.
- Signs of acute infection or positive test result for syphilis, hepatitis A, Toxoplasma gondii, cytomegalovirus, gonorrhea, Chlamydia trachomatis during 30 days before screening.
- Opportunistic infections of the Category C (Centers of Disease Control (CDC), 2008), excluding Kaposi's sarcoma not requiring systemic therapy.
- History of tuberculosis of any localization, or tuberculosis at screening, according to x-ray examination.
- History of malignant tumors (except basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ, eliminated and cured ≥ 5 years ago).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VM-1500 20 mg + ART VM-1500 VM-1500 - 20 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART VM-1500 20 mg + ART Antiretroviral therapy (ART) VM-1500 - 20 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART VM-1500 40 mg + ART VM-1500 VM-1500 - 40 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART VM-1500 40 mg + ART Antiretroviral therapy (ART) VM-1500 - 40 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART Efavirenz 600 mg + ART Antiretroviral therapy (ART) Efavirenz 600 mg (Stage I and Stage II), ART Efavirenz 600 mg + ART Efavirenz Efavirenz 600 mg (Stage I and Stage II), ART
- Primary Outcome Measures
Name Time Method Reduction of HIV-1 RNA level in blood plasma <400 copies/ml 12 weeks Comparison of the percentage of patients with reduced viral load to \< 400 copies/ml at Week 12 in VM-1500 20 mg, VM-1500 40 mg and Efavirenz treatment groups
- Secondary Outcome Measures
Name Time Method Change in the absolute CD8+ lymphocytes count 48 weeks Change in the absolute CD8+ lymphocytes count from Baseline to Week 48 in VM-1500 group with the selected dose and Efavirenz group.
Reduction of HIV-1 RNA level in blood plasma <50 copies/ml 48 weeks Comparison of the percentage of patients with reduced viral load to an undetectable level (\< 50 copies/ml) at Week 48 in VM-1500 group with the selected dose and Efavirenz group.
Change in the absolute CD4+ lymphocytes count 48 weeks Change in the absolute CD4+ lymphocytes count from Baseline to Week 48 in VM-1500 group with the selected dose and Efavirenz group.
The percent of patients with study therapy-resistant HIV-1 development 48 weeks The proportion of patients who develop study therapy-resistant HIV-1 from Baseline to Week 48 in VM-1500 group with the selected dose and Efavirenz group.
Trial Locations
- Locations (13)
Moscow Prevention AIDS Center
🇷🇺Moscow, Russian Federation
Lipetsk regional center for AIDS prevention
🇷🇺Lipetsk, Lipetsk Region, Russian Federation
Perm Regional center for AIDS prevention
🇷🇺Perm, Perm Region, Russian Federation
Ryazan Regional Clinical Dermatovenerologic Dispensary
🇷🇺Ryazan, Ryazan Region, Russian Federation
Republican hospital for AIDS prevention
🇷🇺Kazan, Tatarstan Republic, Russian Federation
Udmurtia Republican hospital for AIDS prevention
🇷🇺Izhevsk, Udmurtia Republic, Russian Federation
Moscow Infectional Clinical Hospital #2
🇷🇺Moscow, Russian Federation
City center for AIDS prevention
🇷🇺Tolyatti, Samara Region, Russian Federation
Volgograd regional center for AIDS prevention
🇷🇺Volgograd, Volgograd Region, Russian Federation
Clinical infectious diseases hospital n.a. S.P. Botkin"
🇷🇺St.Petersburg, Russian Federation
Kaluga regional center for AIDS prevention
🇷🇺Kaluga, Kaluga Region, Russian Federation
St.Petersburg city center for AIDS prevention
🇷🇺St.Petersburg, Russian Federation
Central Scientific Research Institute of Epidemiology
🇷🇺Moscow, Russian Federation