ADORE: Efficacy of DORavirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With NNRTI Resistance

HIV-1-infection Clinical Trial

— ADORE  

Official title:

ADORE: A Single-arm, Phase 3, Pilot Study Investigating the Efficacy of Doravirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With Non-nucleoside Reverse Transcriptase Inhibitor Resistance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04429152
• Other study ID #: EZMiM018
• Status: Recruiting
• Phase: Phase 3
• Start date: February 9, 2021
• Est. completion date: September 2023

Study information

• Verified date: June 2022
• Source: University of Witwatersrand, South Africa
• Contact: Simiso Sokhela, MBBCh
• Phone: +27113585437
• Email: ssokhela[@]wrhi.ac.za
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance

Description:

This is a single-arm, phase 3 pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance.

Approximately 25 male and female participants 18 years and older infected with HIV-1 and experiencing virological failure on efavirenz-based ART will be administered a once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF). The study includes screening and baseline visits, 4 study visits from Week 4 to Week 36, and an end of study visit at Week 48.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults living with HIV-1, 18 years and older

• Viral load 5000 - 60 000 copies/mL on first-line efavirenz-based antiretroviral therapy

• HIV genotype resistance test with first generation NNRTI resistance (e.g. K103N, Y181C, etc as listed in the protocol)

• CD4 > 200 cells/uL

• Creatinine clearance > 50 mL/min

• Body mass = 35 kg.

Exclusion Criteria:

• Resistance to TDF on genotype (K65R)

• "Significant resistance" to doravirine, denoted by a Stanford Score = 15 on genotype

• Virologic failure on any other regimen

• Women who are pregnant at the time of the screening or enrolment visits

• Active tuberculosis and/or are on anti-tuberculous therapy at the time of the screening or enrolment visits

• Taking and cannot discontinue prohibited concomitant medications listed in protocol at least two weeks prior to the enrolment visit and for the duration of the study period.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Doravirine/Lamivudine/Tenofovir
DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination

Locations

Country	Name	City	State
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
South Africa	Sunnyside Office Park	Johannesburg	Gauteng
South Africa	Wits RHI Yeoville Clinic	Johannesburg	Gauteng

Sponsors (1)

Lead Sponsor	Collaborator
Professor Francois Venter

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24	The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded.	24 weeks
Secondary	Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48	Evaluation of viral suppression by recording the proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48	At week 4, 12, 48
Secondary	Change from baseline in plasma CD4 levels at weeks 24 and 48	Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48.	At week 24, 48
Secondary	Emergence of antiretroviral resistance mutations in participants with virological failure	Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure	48 weeks