Efficacy, Safety and Optimal Dose of VM-1500 in Comparison to Efavirenz Added to Standard-of-care Antiretroviral Therapy

NCT02489461 | Completed Phase 2

• 1 other identifier: HIV-VM1500-04
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 13

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.

Conditions

HIV-1-infection

Keywords

HIV

Outcome Measures

Primary Outcomes (1)

• Reduction of HIV-1 RNA level in blood plasma <400 copies/ml

  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

  12 weeks

Secondary Outcomes (5)

• Reduction of HIV-1 RNA level in blood plasma <50 copies/ml

  24 weeks

• Reduction of HIV-1 RNA level in blood plasma <50 copies/ml

  48 weeks

• Change in the absolute CD4+ lymphocytes count

  48 weeks

• Change in the absolute CD8+ lymphocytes count

  48 weeks

• The percent of patients with study therapy-resistant HIV-1 development

  48 weeks

Study Arms (3)

VM-1500 20 mg + ART

EXPERIMENTAL

VM-1500 - 20 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART

Drug: VM-1500; Drug: Antiretroviral therapy (ART)

VM-1500 40 mg + ART

EXPERIMENTAL

VM-1500 - 40 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART

Drug: VM-1500; Drug: Antiretroviral therapy (ART)

Efavirenz 600 mg + ART

ACTIVE COMPARATOR

Efavirenz 600 mg (Stage I and Stage II), ART

Drug: Efavirenz; Drug: Antiretroviral therapy (ART)

Interventions

VM-1500 DRUG

VM-1500 up to 96 weeks

Also known as: Elsulfavirine, Elpida®

VM-1500 20 mg + ART; VM-1500 40 mg + ART

Efavirenz DRUG

Efavirenz up to 48 weeks

Also known as: Stocrin®

Efavirenz 600 mg + ART

Antiretroviral therapy (ART) DRUG

Antiretroviral therapy up to 96 weeks

Also known as: standard antiretroviral therapy of two NNRTIs

Efavirenz 600 mg + ART; VM-1500 20 mg + ART; VM-1500 40 mg + ART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Viriom: lead

Study Sites (13)

Kaluga regional center for AIDS prevention

Kaluga, Kaluga Oblast, Russia

Location

Lipetsk regional center for AIDS prevention

Lipetsk, Lipetsk Oblast, 398043, Russia

Location

Perm Regional center for AIDS prevention

Perm, Perm Krai, 614088, Russia

Location

Ryazan Regional Clinical Dermatovenerologic Dispensary

Ryazan, Ryazan Oblast, 390046, Russia

Location

City center for AIDS prevention

Tolyatti, Samara Oblast, 445846, Russia

Location

Republican hospital for AIDS prevention

Kazan', Tatarstan Republic, 420097, Russia

Location

Udmurtia Republican hospital for AIDS prevention

Izhevsk, Udmurtia Republic, 426067, Russia

Location

Volgograd regional center for AIDS prevention

Volgograd, Volgograd Oblast, 400040, Russia

Location

Central Scientific Research Institute of Epidemiology

Moscow, 105275, Russia

Location

Moscow Infectional Clinical Hospital #2

Moscow, 105275, Russia

Location

Moscow Prevention AIDS Center

Moscow, 129110, Russia

Location

St.Petersburg city center for AIDS prevention

Saint Petersburg, 190103, Russia

Location

Clinical infectious diseases hospital n.a. S.P. Botkin"

Saint Petersburg, 191167, Russia

Location

MeSH Terms

Interventions

elsulfavirine; efavirenz; Antiretroviral Therapy, Highly Active

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Study Officials

• Irina Y Tyrnova

  Viriom,LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2015
• First Posted: July 3, 2015
• Study Start: August 5, 2014
• Primary Completion: April 5, 2016
• Study Completion: September 18, 2017
• Last Updated: September 25, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

RU (13)