Safety and Efficacy of Reduced Versus Standard Dose Efavirenz (EFV) Plus Two Nucleotides in Antiretroviral-naïve Adults.

HIV Infections Clinical Trial

— ENCORE1  

Official title:

A Randomised, Double-blind, Placebo-controlled, Trial to Compare the Safety and Efficacy of Reduced Dose Versus Standard Dose EFV Plus Two Nucleotides (N(t)RTI) in Antiretroviral-naïve HIV-infected Adults Over 96 Weeks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01011413
• Other study ID #: NCHECR-ENCORE1
• Status: Completed
• Phase: Phase 3
• Start date: August 2011
• Est. completion date: August 2014

Study information

• Verified date: February 2020
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Clinical data suggests that the standard dose of the anti-HIV medication, efavirenz (EFV), could be reduced without compromising its effectiveness. Lower drug doses could have fewer side effects and would make EFV more affordable. The purpose of this study is to compare the safety and effectiveness, over 96 weeks, of standard (600mg) versus reduced dose (400mg) EFV in controlling HIV as part of initial combination antiretroviral therapy.

Description:

In this international, multicenter trial, 630 HIV infected patients who have not received any previous treatment for their HIV-infection will be enrolled. Participants will be randomized equally (1:1) to receive Truvada (tenofovir and emtricitabine) with either the standard or reduced dose of EFV. Neither the study doctor nor the participant will know which treatment the participant is receiving. Physical examinations, laboratory analyses and questionnaires will be performed at the 11 study visits at screening, baseline (Week 0), Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96. The primary aim of this study is to compare between treatment groups the proportion of patients with undetectable HIV viral load (HIV RNA < 200 copies/mL) after 48 weeks. Information on immune function, drug adherence, resistance to antiretrovirals, quality of life, mental state and HIV-related conditions will also be collected. Blood samples will be collected for future testing. Interim analyses will be performed when the first 125 participants in each treatment group reach week 24 and when all participants reach week 24. These interim analyses will provide an early check that the reduced dose of EFV suppresses HIV infection as effectively as the standard dose of EFV. A follow-up analysis will be performed when all participants reach week 96.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 636
• Est. completion date: August 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 positive by licensed diagnostic test

• aged >16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)

• 50 < cluster of differentiation (CD)4 <500 cells/µL

• No prior AIDS-defining illness, using the Center for Diseases Control 1993 Case Definition (except pulmonary tuberculosis)

• HIV RNA =1000 copies/mL

• no prior exposure to antiretroviral therapy (ART) (including short course ART for preventing MTCT)

• calculated creatinine clearance (CLCr) more than or equal to 50 mL/min (Cockcroft-Gault formula)

• provision of written informed consent.

Exclusion Criteria:

• the following laboratory values:

• absolute neutrophil count (ANC) <500 cells/µL

• hemoglobin <7.0 g/dL

• platelet count <50,000 cells/µL

• alanine aminotransferase and/or aspartate aminotransferase >5 x upper limit of normal

• pregnant women or nursing mothers

• active opportunistic or malignant disease not under adequate control

• use of immunomodulators within 30 days prior to screening

• use of any prohibited medications

• current alcohol or illicit substance use that might adversely affect study participation

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Efavirenz 600mg
3 x EFV 200 milligram (mg) tablets once daily
• Efavirenz 400mg
2 x EFV 200 milligram (mg) tablets plus 1x matched EFV placebo tablet once daily

Locations

Country	Name	City	State
Australia	St Vincent's Hospital	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Country where clinical trial is conducted

Australia, 

References & Publications (2)

ENCORE1 Study Group, Carey D, Puls R, Amin J, Losso M, Phanupak P, Foulkes S, Mohapi L, Crabtree-Ramirez B, Jessen H, Kumar S, Winston A, Lee MP, Belloso W, Cooper DA, Emery S. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week dat — View Citation

ENCORE1 Study Group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2014 Apr 26;383(9927):1474-1482. doi: 10.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Plasma HIV-1 RNA <200 Copies/mL 48 Weeks After Randomisation	Percentage of participants in each of the treatment arms with centrally quantified plasma HIV-1 RNA viral load <200 copies/mL 48 weeks after randomisation.	48 weeks
Secondary	Percentage of Participants With Plasma HIV-1 RNA <400 Copies/mL and <50 Copies/mL at 48 and 96 Weeks After Randomisation	Percentage of participants in each of the two treatment arms with plasma HIV-1 RNA <400 copies/mL and <50 copies/mL at 48 and 96 weeks after randomisation	Baseline and 2 years
Secondary	Mean Change From Baseline in CD4+ T-cell Count	Mean change from baseline to week 96 in CD4+ T-cell count/mm3 between the two treatment arms	Baseline and 2 years
Secondary	Clinical Endpoints: Opportunistic Disease or Death, and Serious Non-AIDS-defining Events and Non-AIDS-related Mortality	Number of participants in each randomised arm diagnosed with a serious non-AIDS defining event, who die from an AIDS-defining event, who die from a non-AIDS-defining event	up to 2 years
Secondary	Change From Baseline in Metabolic Endpoints	Change from baseline to week 96 in fasted total cholesterol, high density cholesterol and low density cholesterol, and glucose between randomised treatment arms	Baseline and 2 years
Secondary	Adherence: Median Scores of Self-reported Adherence to Randomised Study Medications	AIDS Clinical Trials Group (ACTG) 7-day adherence questionnaire scores. Maximum value is all pills taken every day; minimum value is no pills taken per day. Higher scores indicate a better outcome.	2 years
Secondary	Change From Baseline in Fasted Insulin Levels	Change from baseline to week 96 in fasted insulin levels	Baseline and 2 years
Secondary	Change in Selected Serum Biochemical Parameters	Change from baseline to week 96 in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels between randomised treatment arms	Baseline and 2 years
Secondary	Change From Baseline in Estimate Creatinine Clearance	Change from baseline to week 96 in estimate creatinine clearance between randomised treatment arms	Baseline and 2 years
Secondary	Steady-state Efavirenz Concentrations	Steady-state efavirenz mid-dosing interval plasma concentrations	Week 4

External Links

•   Kirby Institute (formerly National Centre for HIV Epidemiology and Clinical Research)