Clinical trial NCT02489461: Efficacy, Safety and Optimal Dose of VM-1500 in Comparison to Efavirenz Added to Standard-of-care Antiretroviral Therapy
Official title: International, Multicenter, Randomized, Partially Blind Study to Evaluate Efficacy, Safety and Selection of the Optimal Dose for VM-1500 in Comparison to Efavirenz in Combination With Two NRTIs in Treatment-naïve, HIV-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV-1-infection
Keywords: HIV
Lead sponsor: Viriom
Sponsor class: INDUSTRY
First posted: 2015-07-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Signed Patient Information and Informed Consent Form.
2. Males and females, age ≥ 18 years.
3. HIV-1 infection, confirmed serologically in IFA or immunoblot analysis (or documented HIV-1 infection).
4. Clinically stable HIV infection (clinical stages 1 or 2 according to the WHO classification).
5. 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).
6. HIV-1 RNA plasma level ≥ 5 000 copies/ml at screening.
7. СD4+ Т-cells number \> 200 cells/mm3 at screening.
8. 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:

1. 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.
2. History of antiretroviral therapy (ART), including for the prevention of vertical transmission of HIV.
3. Acute hepatitis or hepatic cirrhosis of any etiology; anti-HCV antibodies or HBsAg at screening.
4. Signs of acute infection or positive test result for syphilis, hepatitis A, Toxoplasma gondii, cytomegalovirus, gonorrhea, Chlamydia trachomatis during 30 days before screening.
5. Opportunistic infections of the Category C (Centers of Disease Control (CDC), 2008), excluding Kaposi's sarcoma not requiring systemic therapy.
6. History of tuberculosis of any localization, or tuberculosis at screening, according to x-ray examination.
7. History of malignant tumors (except basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ, eliminated and cured ≥ 5 years ago).

Primary outcomes:
measure: Reduction of HIV-1 RNA level in blood plasma <400 copies/ml
timeFrame: 12 weeks
Secondary outcomes:
measure: Reduction of HIV-1 RNA level in blood plasma <50 copies/ml
timeFrame: 24 weeks
measure: Reduction of HIV-1 RNA level in blood plasma <50 copies/ml
timeFrame: 48 weeks
measure: Change in the absolute CD4+ lymphocytes count
timeFrame: 48 weeks
measure: Change in the absolute CD8+ lymphocytes count
timeFrame: 48 weeks
measure: The percent of patients with study therapy-resistant HIV-1 development
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Kaluga
country: Russian Federation
facility: Kaluga regional center for AIDS prevention
state: Kaluga Region
city: Lipetsk
country: Russian Federation
facility: Lipetsk regional center for AIDS prevention
state: Lipetsk Region
city: Perm
country: Russian Federation
facility: Perm Regional center for AIDS prevention
state: Perm Region
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Dermatovenerologic Dispensary
state: Ryazan Region
city: Tolyatti
country: Russian Federation
facility: City center for AIDS prevention
state: Samara Region
city: Kazan
country: Russian Federation
facility: Republican hospital for AIDS prevention
state: Tatarstan Republic
city: Izhevsk
country: Russian Federation
facility: Udmurtia Republican hospital for AIDS prevention
state: Udmurtia Republic
city: Volgograd
country: Russian Federation
facility: Volgograd regional center for AIDS prevention
state: Volgograd Region
city: Moscow
country: Russian Federation
facility: Central Scientific Research Institute of Epidemiology
city: Moscow
country: Russian Federation
facility: Moscow Infectional Clinical Hospital #2
city: Moscow
country: Russian Federation
facility: Moscow Prevention AIDS Center
city: St.Petersburg
country: Russian Federation
facility: St.Petersburg city center for AIDS prevention
city: St.Petersburg
country: Russian Federation
facility: Clinical infectious diseases hospital n.a. S.P. Botkin"
Study officials:
affiliation: Viriom,LLC
name: Irina Y Tyrnova
role: STUDY_CHAIR
References: