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

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ClinicalTrials.gov Identifier: NCT04429152
Recruitment Status : Recruiting
First Posted : June 12, 2020
Last Update Posted : November 4, 2020
Sponsor:
Information provided by (Responsible Party):
Willem Daniel Francois Venter, University of Witwatersrand, South Africa

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : November 10, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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 Name: Delstrigo




Primary Outcome Measures :
  1. Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 48 weeks ]
    Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04429152


Contacts
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Contact: Simiso Sokhela, MBBCh +27113585437 ssokhela@wrhi.ac.za
Contact: Bronwyn Bosch, MBBCh +27113585300 bbosch@wrhi.ac.za

Locations
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South Africa
Charlotte Maxeke Johannesburg Academic Hospital Recruiting
Johannesburg, Gauteng, South Africa, 2196
Contact: Natasha Arulappan    +27113585542    gakpomiemie@wrhi.ac.za   
Contact: Nonkululeko Mashabane, BPharm    +27113585543      
Sunnyside Office Park Not yet recruiting
Johannesburg, Gauteng, South Africa
Contact: Bronwyn Bosch, MBBCh    +27113585300    bbosch@wrhi.ac.za   
Contact: Godspower Akpomiemie, MPH    +2711358 5370    gakpomiemie@wrhi.ac.za   
Wits RHI Yeoville Clinic Not yet recruiting
Johannesburg, Gauteng, South Africa
Contact: Simiso Sokhela, MBBCh    +27113585500    ssokhela@wrhi.ac.za   
Contact: Nonkululeko Mashabane, BPharm    +27113585543    nmashabane@wrhi.ac.za   
Principal Investigator: Simiso Sokhela, MBBCh         
Sub-Investigator: Nomathemba Chandiwana, MBBCh         
Sponsors and Collaborators
Willem Daniel Francois Venter
Investigators
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Principal Investigator: Simiso Sokhela, MBBCh Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)
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Responsible Party: Willem Daniel Francois Venter, Divisional Director: Ezintsha, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT04429152    
Other Study ID Numbers: EZMiM018
First Posted: June 12, 2020    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020

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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 Willem Daniel Francois Venter, University of Witwatersrand, South Africa:
Virological failure, first-line antiretroviral therapy
Doravirine
Delstrigo
Additional relevant MeSH terms:
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Tenofovir
Lamivudine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents