Efficacy, Safety and Optimal Dose of VM-1500 in Comparison to Efavirenz Added to Standard-of-care Antiretroviral Therapy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VM-1500 20 mg + ART VM-1500 - 20 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART |
Drug: VM-1500
VM-1500 up to 96 weeks
Other Names:
Drug: Antiretroviral therapy (ART)
Antiretroviral therapy up to 96 weeks
Other Names:
|
| Experimental: VM-1500 40 mg + ART VM-1500 - 40 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART |
Drug: VM-1500
VM-1500 up to 96 weeks
Other Names:
Drug: Antiretroviral therapy (ART)
Antiretroviral therapy up to 96 weeks
Other Names:
|
| Active Comparator: Efavirenz 600 mg + ART Efavirenz 600 mg (Stage I and Stage II), ART |
Drug: Efavirenz
Efavirenz up to 48 weeks
Other Names:
Drug: Antiretroviral therapy (ART)
Antiretroviral therapy up to 96 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- Reduction of HIV-1 RNA level in blood plasma <50 copies/ml [24 weeks]
Comparison of the percentage of patients with reduced viral load to an undetectable level (< 50 copies/ml) at Week 24 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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.
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History of antiretroviral therapy (ART), including for the prevention of vertical transmission of HIV.
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Acute hepatitis or hepatic cirrhosis of any etiology; anti-HCV antibodies or HBsAg at screening.
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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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kaluga regional center for AIDS prevention | Kaluga | Kaluga Region | Russian Federation | |
| 2 | Lipetsk regional center for AIDS prevention | Lipetsk | Lipetsk Region | Russian Federation | 398043 |
| 3 | Perm Regional center for AIDS prevention | Perm | Perm Region | Russian Federation | 614088 |
| 4 | Ryazan Regional Clinical Dermatovenerologic Dispensary | Ryazan | Ryazan Region | Russian Federation | 390046 |
| 5 | City center for AIDS prevention | Tolyatti | Samara Region | Russian Federation | 445846 |
| 6 | Republican hospital for AIDS prevention | Kazan | Tatarstan Republic | Russian Federation | 420097 |
| 7 | Udmurtia Republican hospital for AIDS prevention | Izhevsk | Udmurtia Republic | Russian Federation | 426067 |
| 8 | Volgograd regional center for AIDS prevention | Volgograd | Volgograd Region | Russian Federation | 400040 |
| 9 | Central Scientific Research Institute of Epidemiology | Moscow | Russian Federation | 105275 | |
| 10 | Moscow Infectional Clinical Hospital #2 | Moscow | Russian Federation | 105275 | |
| 11 | Moscow Prevention AIDS Center | Moscow | Russian Federation | 129110 | |
| 12 | St.Petersburg city center for AIDS prevention | St.Petersburg | Russian Federation | 190103 | |
| 13 | Clinical infectious diseases hospital n.a. S.P. Botkin" | St.Petersburg | Russian Federation | 191167 |
Sponsors and Collaborators
- Viriom
Investigators
- Study Chair: Irina Y Tyrnova, Viriom,LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HIV-VM1500-04