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

• ClinicalTrials.gov Identifier: NCT02489461
• Recruitment Status: Completed
• First Posted: July 3, 2015
• Last Update Posted: September 25, 2018
• Sponsor: Viriom
• Information provided by (Responsible Party): Viriom

Tracking Information

• First Submitted Date: June 18, 2015
• First Posted Date: July 3, 2015
• Last Update Posted Date: September 25, 2018
• Actual Study Start Date: August 5, 2014
• Actual Primary Completion Date: April 5, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2018)

Reduction of HIV-1 RNA level in blood plasma <400 copies/ml [ Time Frame: 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

Original Primary Outcome Measures (submitted: June 30, 2015)

• Optimal dose selection for VM-1500 in combination with two nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) based on analysis of AEs, laboratory values, subjects' diaries. [ Time Frame: 48 weeks ]
• Efficacy evaluation of VM-1500 (optimal dose selected at Stage I) in combination with two NRTIs, as compared to Efavirenz in combination with two NRTIs based on analysis of viral load. [ Time Frame: 52 weeks ]
• Safety evaluation of VM-1500 (optimal dose selected at Stage I) in combination with two NRTIs, as compared to Efavirenz in combination with two NRTIs based on analysis of AEs, laboratory values and subjects' diaries. [ Time Frame: 52 weeks ]

Current Secondary Outcome Measures (submitted: September 21, 2018)

• Reduction of HIV-1 RNA level in blood plasma <50 copies/ml [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: HIV-1-infection

Intervention

• Drug: VM-1500
  VM-1500 up to 96 weeks
  Other Names:

  • Elsulfavirine
  • Elpida®
• Drug: Efavirenz
  Efavirenz up to 48 weeks
  Other Name: Stocrin®
• Drug: Antiretroviral therapy (ART)
  Antiretroviral therapy up to 96 weeks
  Other Name: standard antiretroviral therapy of two NNRTIs

Study Arms

• Experimental: VM-1500 20 mg + ART
  VM-1500 - 20 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART
  Interventions:

  • Drug: VM-1500
  • Drug: Antiretroviral therapy (ART)
• Experimental: VM-1500 40 mg + ART
  VM-1500 - 40 mg (Stage I), then optimal dose (Stage II and Open-Label Stage), ART
  Interventions:

  • Drug: VM-1500
  • Drug: Antiretroviral therapy (ART)
• Active Comparator: Efavirenz 600 mg + ART
  Efavirenz 600 mg (Stage I and Stage II), ART
  Interventions:

  • Drug: Efavirenz
  • Drug: Antiretroviral therapy (ART)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2015): 150
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 18, 2017
• Actual Primary Completion Date: April 5, 2016 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT02489461
• Other Study ID Numbers: HIV-VM1500-04
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Viriom
• Original Responsible Party: Same as current
• Current Study Sponsor: Viriom
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Irina Y Tyrnova; Viriom,LLC

• PRS Account: Viriom
• Verification Date: September 2018