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

HIV-1-infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02489461
• Other study ID #: HIV-VM1500-04
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 5, 2014
• Est. completion date: September 18, 2017

Study information

• Verified date: September 2018
• Source: Viriom
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 18, 2017
• Est. primary completion date: April 5, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. ?D4+ ?-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).

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• VM-1500
VM-1500 up to 96 weeks
• Efavirenz
Efavirenz up to 48 weeks
• Antiretroviral therapy (ART)
Antiretroviral therapy up to 96 weeks

Locations

Country	Name	City	State
Russian Federation	Udmurtia Republican hospital for AIDS prevention	Izhevsk	Udmurtia Republic
Russian Federation	Kaluga regional center for AIDS prevention	Kaluga	Kaluga Region
Russian Federation	Republican hospital for AIDS prevention	Kazan	Tatarstan Republic
Russian Federation	Lipetsk regional center for AIDS prevention	Lipetsk	Lipetsk Region
Russian Federation	Central Scientific Research Institute of Epidemiology	Moscow
Russian Federation	Moscow Infectional Clinical Hospital #2	Moscow
Russian Federation	Moscow Prevention AIDS Center	Moscow
Russian Federation	Perm Regional center for AIDS prevention	Perm	Perm Region
Russian Federation	Ryazan Regional Clinical Dermatovenerologic Dispensary	Ryazan	Ryazan Region
Russian Federation	Clinical infectious diseases hospital n.a. S.P. Botkin"	St.Petersburg
Russian Federation	St.Petersburg city center for AIDS prevention	St.Petersburg
Russian Federation	City center for AIDS prevention	Tolyatti	Samara Region
Russian Federation	Volgograd regional center for AIDS prevention	Volgograd	Volgograd Region

Sponsors (1)

Lead Sponsor	Collaborator
Viriom

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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