Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide
NCT ID: NCT04636437
Last Updated: 2025-07-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
147 participants
INTERVENTIONAL
2021-07-27
2024-10-18
Brief Summary
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Detailed Description
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As originally designed, the trial's target population included individuals with an unintentional \>10% weight gain in the 1-3 years after initiating or switching to an INSTI-based treatment regimen. Due to not meeting accrual targets during the first year of enrollment (July 2021 - July 2022), the trial protocol was updated to amend the target population (and associated eligibility criteria) to individuals with obesity (a screening body mass index \[BMI\] of ≥30 kg/m2) irrespective of weight history on INSTI-based ART. This update was implemented on November 17, 2022, at which time 64 participants had enrolled under the original trial design. The remaining participants enrolled using the revised eligibility criterion.
At a planned interim analysis in 2023, the method of blinded sample size re-estimation was used to assess if the trial's primary objective could be met with a sample size smaller than originally planned (n=222). Based on the pooled (e.g. over all arms) standard deviation of the primary outcome (weight change at 48 weeks), 150 participants would provide over 80% statistical power to detect the originally hypothesized 5% points change in weight between arms, assuming that this interim estimate was representative of the true variability about the primary outcome. As a result, the accrual goal was adjusted accordingly. The trial closed to enrollment in October 2024, having reached 147 participants.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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DOR 100 mg + TAF/FTC
By mouth daily with or without food
Doravirine 100 Mg
Participants received a 100 mg tablet by mouth daily with or without food.
Integrase strand transfer inhibitors
INSTIs were acquired through the standard of care locally.
DOR 100 mg + TDF/FTC
By mouth daily with or without food
Doravirine 100 Mg
Participants received a 100 mg tablet by mouth daily with or without food.
tenofovir disproxil fumarate/emtricitabine
NRTIs (TDF/FTC) were acquired through the standard of care locally.
Continuation of INSTI+TAF/FTC
By mouth daily with or without food
Integrase strand transfer inhibitors
INSTIs were acquired through the standard of care locally.
Tenofovir alafenamide/emtricitabine
NRTIs (TAF/FTC) were acquired through the standard of care locally.
Interventions
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Doravirine 100 Mg
Participants received a 100 mg tablet by mouth daily with or without food.
Integrase strand transfer inhibitors
INSTIs were acquired through the standard of care locally.
Tenofovir alafenamide/emtricitabine
NRTIs (TAF/FTC) were acquired through the standard of care locally.
tenofovir disproxil fumarate/emtricitabine
NRTIs (TDF/FTC) were acquired through the standard of care locally.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
HIV-1, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load. If a rapid HIV test or any FDA-approved HIV-1 E/CIA test kit is not available, two HIV-1 RNA values ≥2000 copies/mL at least 24 hours apart may be performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or by any non-US laboratory that is DAIDS Good Clinical Laboratory Practice (GCLP) compliant and, if performing HIV-1 RNA testing, is Virology Quality Assurance (VQA)-certified.
Currently on a bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL) + TAF/FTC regimen with ≥48 weeks prior to study entry.
Ability to acquire NRTIs (TAF/FTC or TDF/FTC) and INSTI through usual care for the duration of the study.
A BMI ≥30 kg/m2 at screening. No known plans to change or to initiate medications known to be associated with significant weight changes during study period.
Agree to adhere to assigned ART during the study period At least one HIV-1 RNA level \<50 copies/mL (or below the lower limit of HIV-1 RNA detection available at the site if the lower limit of detection is \>50) performed in the 48 weeks prior (≤48 weeks) to study screening, and at least one HIV-1 RNA level \<50 copies/mL ≥48 weeks prior to study screening, using an FDA-approved assay performed by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is VQA certified.
Screening HIV-1 RNA \<50 copies/mL (or below the lower limit of HIV-1 RNA detection available if the lower limit of detection is \>50) performed within 45 days prior to study entry by any US laboratory that possesses a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is VQA certified.
For participants capable of becoming pregnant, negative serum or urine pregnancy test within 45 days prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/ CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
Participants engaging in sexual activity and capable of becoming pregnant must agree to use contraception while on study drug (approximately 48 weeks) and for 8 weeks after the end of the study. At least one of the following contraceptive methods must be used:
* Intrauterine device (IUD)
* Hormone-based contraceptive
* Partner sterilization (i.e., vasectomy) and is the sole partner for the participant.
Transgender participants who are currently taking hormones must be on a stable hormone dose for \>12 weeks prior to study entry. Transgender participants should not have active plans to change their hormone regimen or dose during the study period.
The following laboratory values obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs:
* Absolute neutrophil count (ANC) \>750 cells/mm3
* Hemoglobin \>10 g/dL for males and \>9 g/dL for females (based on sex at birth)
* Calculated creatinine clearance ≥50 mL/min as estimated by the CKD-EPI equation (a calculator is available at: https://qxmd.com/calculate/calculator\_251/egfr-using-ckd-epi)
* Aspartate aminotransferase (AST) (SGOT) \<3x ULN
* Alanine aminotransferase (ALT) (SGPT) \<3x ULN
Exclusion Criteria
Historical or current evidence of major mutations associated with NNRTI resistance.
History of prior virologic failure in the opinion of the site investigator. For example, a confirmed plasma HIV-1 RNA \>1000 copies/mL after having achieved viral suppression.
Prior exposure to single-dose nevirapine for the prevention of parent-to-child transmission of HIV.
Any history of significant renal toxicity while taking TDF (as determined by the site investigator).
Currently breast-feeding or pregnant, or intending to become pregnant during the duration of the study.
Current use, use in the 4 weeks preceding study entry, or anticipated use of prohibited drugs during the study period.
Anticipated start or cessation of any of the following drugs during the study period:
* Antipsychotics (e.g., clozapine, olanzapine, risperidone, etc.) and antidepressants (tricyclic antidepressants, e.g., amitriptyline, nortriptyline, etc.; selective serotonin reuptake inhibitors, e.g., fluoxetine, paroxetine, sertraline, etc.; and monoamine oxidase inhibitors, e.g., selegiline) associated with weight gain
* Anticonvulsants/mood stabilizers associated with weight gain (e.g., lithium, valproic acid) or weight loss (e.g., topiramate)
* Thyroid replacement hormones
* Anti-diabetic agents known to cause weight loss (e.g., GLP-1 receptor agonists such as exenatide, dulaglutide, semaglutide, metformin, and SGLT-2 inhibitors such as canagliflozin, dapagliflozin, etc.).
Planning to undergo bariatric surgery or initiate significant dietary or exercise changes within the study period (e.g., structured weight loss programs such as Weight Watchers), as determined by participant report.
Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation.
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with ability to adhere to study requirements, or cessation of regular methamphetamine use, as determined by the site investigator, within 60 days prior to study entry.
Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
A history of a diagnosis of osteoporosis or osteopenia.
18 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
NETWORK
Responsible Party
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Principal Investigators
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John Koethe
Role: STUDY_CHAIR
Vanderbilt University Medical Center
Locations
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Alabama CRS (31788)
Birmingham, Alabama, United States
UCLA CARE Center CRS (601)
Los Angeles, California, United States
UCSD Antiviral Research Center CRS (701)
San Diego, California, United States
Ucsf Hiv/Aids Crs (801)
San Francisco, California, United States
Harbor-UCLA CRS (603)
Torrance, California, United States
University of Colorado Hospital CRS (6101)
Aurora, Colorado, United States
Whitman-Walker Institute, Inc. CRS (31791)
Washington D.C., District of Columbia, United States
The Ponce de Leon Center CRS (5802)
Atlanta, Georgia, United States
Northwestern University CRS (2701)
Chicago, Illinois, United States
Johns Hopkins University CRS (201)
Baltimore, Maryland, United States
Massachusetts General Hospital (MGH) CRS (101)
Boston, Massachusetts, United States
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, United States
Washington University Therapeutics (WT) CRS (2101)
St Louis, Missouri, United States
New Jersey Medical School Clinical Research Center CRS (31786)
Newark, New Jersey, United States
Weill Cornell Chelsea CRS (7804)
New York, New York, United States
Columbia Physicians and Surgeons (P&S) CRS (30329)
New York, New York, United States
Weill Cornell Upton CRS (7803)
New York, New York, United States
University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)
Rochester, New York, United States
Chapel Hill CRS (3201)
Chapel Hill, North Carolina, United States
Greensboro CRS (3203)
Greensboro, North Carolina, United States
Cincinnati CRS (2401)
Cincinnati, Ohio, United States
Case CRS (2501)
Cleveland, Ohio, United States
Ohio State University CRS (2301)
Columbus, Ohio, United States
Penn Therapeutics CRS (6201)
Philadelphia, Pennsylvania, United States
Vanderbilt Therapeutics (VT) CRS (3652)
Nashville, Tennessee, United States
Houston AIDS Research Team CRS (31473)
Houston, Texas, United States
University of Washington Positive Research CRS (1401)
Seattle, Washington, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Informed Consent Form
Document Type: Statistical Analysis Plan
Related Links
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Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)
Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0 - January 2010)
CKD-EPI Creatinine Equation (2021)
Other Identifiers
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ACTG A5391
Identifier Type: -
Identifier Source: org_study_id
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