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

• Sponsor: Professor Francois Venter (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04429152
• Collaborator: (none)
• Enrollment: 25
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 30.7
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
HIV-1-infection	Drug: Doravirine/Lamivudine/Tenofovir	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 9, 2021
• Anticipated Primary Completion Date: Sep 1, 2023
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doravirine Once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF).	Drug: Doravirine/Lamivudine/Tenofovir; DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination; Other Names: Delstrigo

Outcome Measures

Primary Outcome Measures

1. Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24 [24 weeks]

   The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded.

Secondary Outcome Measures

1. Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48 [At week 4, 12, 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

2. Change from baseline in plasma CD4 levels at weeks 24 and 48 [At week 24, 48]

   Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48.

3. Emergence of antiretroviral resistance mutations in participants with virological failure [48 weeks]

   Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng	South Africa	2196
2	Sunnyside Office Park	Johannesburg	Gauteng	South Africa
3	Wits RHI Yeoville Clinic	Johannesburg	Gauteng	South Africa

Sponsors and Collaborators

• Professor Francois Venter

Investigators

• Principal Investigator: Simiso Sokhela, MBBCh, Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Professor Francois Venter, Divisional Director: Ezintsha, University of Witwatersrand, South Africa
• ClinicalTrials.gov Identifier: NCT04429152
• Other Study ID Numbers: EZMiM018
• First Posted: Jun 12, 2020
• Last Update Posted: Jun 7, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Professor Francois Venter, Divisional Director: Ezintsha, University of Witwatersrand, South Africa: Virological failure, first-line antiretroviral therapy; Doravirine; Delstrigo
• Additional relevant MeSH terms: Tenofovir; Lamivudine

Study Results

No Results Posted as of Jun 7, 2022