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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: VM-1500; Drug: Antiretroviral therapy (ART); Drug: Efavirenz

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 Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 105275
    • Central Scientific Research Institute of Epidemiology
  • Moscow, Russian Federation, 105275
    • Moscow Infectional Clinical Hospital #2
  • Moscow, Russian Federation, 129110
    • Moscow Prevention AIDS Center
  • St.Petersburg, Russian Federation, 190103
    • St.Petersburg city center for AIDS prevention
  • St.Petersburg, Russian Federation, 191167
    • Clinical infectious diseases hospital n.a. S.P. Botkin"
  • Kaluga Region
    • Kaluga, Kaluga Region, Russian Federation
      • Kaluga regional center for AIDS prevention
  • Lipetsk Region
    • Lipetsk, Lipetsk Region, Russian Federation, 398043
      • Lipetsk regional center for AIDS prevention
  • Perm Region
    • Perm, Perm Region, Russian Federation, 614088
      • Perm Regional center for AIDS prevention
  • Ryazan Region
    • Ryazan, Ryazan Region, Russian Federation, 390046
      • Ryazan regional clinical dermatovenerologic dispensary
  • Samara Region
    • Tolyatti, Samara Region, Russian Federation, 445846
      • City center for AIDS prevention
  • Tatarstan Republic
    • Kazan, Tatarstan Republic, Russian Federation, 420097
      • Republican hospital for AIDS prevention
  • Udmurtia Republic
    • Izhevsk, Udmurtia Republic, Russian Federation, 426067
      • Udmurtia Republican hospital for AIDS prevention
  • Volgograd Region
    • Volgograd, Volgograd Region, Russian Federation, 400040
      • Volgograd regional center for AIDS prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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: Elpida®; Elsulfavirine; Drug: Antiretroviral therapy (ART); Antiretroviral therapy up to 96 weeks; Other Names: standard antiretroviral therapy of two NNRTIs
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: Elpida®; Elsulfavirine; Drug: Antiretroviral therapy (ART); Antiretroviral therapy up to 96 weeks; Other Names: standard antiretroviral therapy of two NNRTIs
Active Comparator: Efavirenz 600 mg + ART; Efavirenz 600 mg (Stage I and Stage II), ART	Drug: Antiretroviral therapy (ART); Antiretroviral therapy up to 96 weeks; Other Names: standard antiretroviral therapy of two NNRTIs; Drug: Efavirenz; Efavirenz up to 48 weeks; Other Names: Stocrin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of HIV-1 RNA level in blood plasma <50 copies/ml	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.	24 weeks
Reduction of HIV-1 RNA level in blood plasma <50 copies/ml	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.	48 weeks
Change in the absolute CD4+ lymphocytes count	Change in the absolute CD4+ lymphocytes count from Baseline to Week 48 in VM-1500 group with the selected dose and Efavirenz group.	48 weeks
Change in the absolute CD8+ lymphocytes count	Change in the absolute CD8+ lymphocytes count from Baseline to Week 48 in VM-1500 group with the selected dose and Efavirenz group.	48 weeks
The percent of patients with study therapy-resistant HIV-1 development	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.	48 weeks

Collaborators and Investigators

• Sponsor: Viriom
• Investigators: Study Chair: Irina Y Tyrnova, Viriom,LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2014
• Primary Completion (Actual): April 5, 2016
• Study Completion (Actual): September 18, 2017

Study Registration Dates

• First Submitted: June 18, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 3, 2015

Study Record Updates

• Last Update Posted (Actual): September 25, 2018
• Last Update Submitted That Met QC Criteria: September 21, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: HIV
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz; Anti-Retroviral Agents; Elsulfavirine
• Other Study ID Numbers: HIV-VM1500-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No