Clinical trial NCT03945981: Rapid Test and Treat Dolutegravir Plus Lamivudine Study in Newly Diagnosed Human Immunodeficiency Virus (HIV)-1 Infected Adults
Official title: A Phase 3b Multi-center, Open Label, Single Arm, 52-week Study, Evaluating the Feasibility, Efficacy and Safety of Rapid Test and Treat Intervention in Newly Diagnosed HIV-1 Infected Adults Using a Fixed Dose Combination of Dolutegravir Plus Lamivudine (DOVATO) as a First Line Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: GSK3515864, dolutegravir, Dovato, lamivudine, 3TC, HIV-1, Test and Treat
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2019-05-10
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will receive 50 mg DTG + 300 mg 3TC FDC, participants will administer one tablet once daily (OD) orally with or without food.
Primary purpose: TREATMENT

Brief summary: Early initiation of antiretroviral therapy (ART) reduces morbidity and mortality for individuals infected with HIV. Suppressing viral replication with ART also reduces the potential for transmission of HIV. Hence, ART is recommended for all persons with HIV viremia regardless of cluster of differentiation 4 (CD4) count. This is an open-label single arm which will evaluate the feasibility, efficacy and safety using a fixed dose combination (FDC) of Dolutegravir (DTG) plus Lamivudine (3TC) as a first line regimen of a rapid Test and Treat model of care over 48 weeks. Participants with new and confirmed diagnosed HIV-1 who are willing to start study treatment immediately following diagnosis will receive 50 milligram (mg) DTG + 300 (mg) 3TC FDC as first line therapy without waiting for screening laboratory results, at the Screening/Day 1 Visit. The total duration for the study will be 52 weeks and 4 weeks of follow up period if required. This study will be conducted in United States (US) with approximately 120 participants.


Eligibility criteria: Inclusion Criteria:

* Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions.
* Eligible participants must be likely to complete the study as planned.
* Eligible participants must be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g. no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).
* Participant must be more than or equal to 18 at the time of signing the informed consent.
* Participants must have a new and confirmed diagnosis of HIV-1 infection and are willing to initiate ART immediately (or, for those participants referred from another site, within 14 days of initial diagnosis at the external clinic/testing center).
* Participant must have an initial positive rapid HIV test and participant has a second positive confirmatory rapid HIV test, using a test kit from a different manufacturer than the first test or participant has been identified as HIV-1 infected using an FDA-approved 4th generation assay antigen/antibody combination immunoassay or 3rd generation immunoassay that detects and differentiates HIV-1 and HIV-2 antibodies; participant has a confirmatory HIV western blot or an HIV-1 RNA or participant has a positive FDA-approved 4th generation assay and a positive 3rd generation immunoassay that detects and differentiates HIV-1 and HIV-2 antibodies.
* Antiretroviral-naïve. Participants who received HIV post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) in the past are allowed as long as the last PEP/PrEP dose was more than 6 months from HIV diagnosis or there is documented HIV seronegativity at least 2 months after the last prophylactic dose and prior to the date of HIV diagnosis.
* Male and/or female participants.
* Participants who are female at birth are eligible to participate if at least one of the following conditions applies: Not pregnant \[as confirmed by a negative urine human chorionic gonadotropin (hCG) test at Screening/Day 1.
* Pregnant and post the first trimester (the physician and patient should decide whether enrolling in this study is in the participants best interest during the consent process)
* Not a participant of childbearing potential (POCBP) or a POCBP agrees to follow the contraceptive guidance, is currently taking hormonal contraceptives and continues for at least 2 weeks after the last dose of study medication. Participants who are female at birth and who are in the following categories are not considered POCBP, premenarchal, premenopausal female with one of the following: documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy or postmenopausal, a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in participants who are female at birth and not using hormonal contraception or hormonal replacement therapy (HRT); participants who are female at birth on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the study.
* Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

* Participants who are breastfeeding, plan to become pregnant or breastfeed during the study.
* Participants who are in their first trimester of pregnancy.
* HIV-1 drug resistance genotype test results are known prior to Screening/Day 1.
* Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except for esophageal candidiasis and cutaneous Kaposi's sarcoma not requiring systemic therapy.
* Participants with known or suspected Hepatitis B infection.
* Participants with known or suspected severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Participants with known moderate to severe renal impairment (creatinine clearance less than 30ml/minute per 1.73 square meter);
* Participant with ongoing malignancy other than basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the participant.
* Participants who in the investigator's judgment, poses a significant suicidality risk.
* Participants with any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
* Participants with substance abuse disorders or social restraints that the Investigator considers to be possible deterrents to successful initiation of ART.
* Participants with history or presence of allergy or intolerance to the study drugs or their components.
* Participants with treatment with any of the following agents within 28 days of the first dose of study treatment, radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
* Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
* Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study treatment.

Primary outcomes:
measure: Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) Regardless of Antiretroviral Therapy (ART) Regimen at Week 24 by ITT-E Missing = Failure Analysis
timeFrame: At Week 24
Secondary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL Regardless of ART Regimen at Week 48 by ITT-E Missing = Failure Analysis
timeFrame: At Week 48
measure: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL Using Food and Drug Administration (FDA) Snapshot Algorithm
timeFrame: At Week 24 and Week 48
measure: Time to Viral Suppression (HIV-1 RNA<50 c/mL) for Participants Who Had HIV-1 RNA >= 50 c/mL at Baseline
timeFrame: Up to Week 48
measure: Number of Participants Who Changed First Line Regimen of DTG + 3TC FDC Due to Baseline Laboratory Results or HIV-1 Resistance Mutation Results
timeFrame: Up to Week 48
measure: Number of Participants With Treatment-emergent Genotypic Resistance
timeFrame: Up to Week 48
measure: Number of Participants With Treatment-emergent Phenotypic Resistance
timeFrame: Up to Week 48
measure: Number of Participants With Any Serious Adverse Events (SAEs) and Any Common (>=2%) Non-serious Adverse Events (Non-SAEs) Under Treatment With DTG + 3TC FDC
timeFrame: Up to Week 48
measure: Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities Under Treatment With DTG + 3TC FDC
timeFrame: Up to Week 48
measure: Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities Under Treatment With DTG + 3TC FDC
timeFrame: Up to Week 48
measure: Number of Participants Who Discontinued the Study Treatment (DTG+3TC FDC) Due to AEs
timeFrame: Up to Week 48
measure: Number of Participants Who Discontinued the Study Treatment (DTG+3TC FDC) Due to Drug-related AEs
timeFrame: Up to Week 48
measure: Change From Baseline in Cluster of Differentiation (CD4+) Cell Counts for Participants Under Treatment With DTG + 3TC FDC
timeFrame: Baseline (Day 1) and Week 24 and Week 48
measure: Change From Baseline in CD4+/CD8+ Cell Count Ratio for Participants Under Treatment With DTG + 3TC FDC
timeFrame: Baseline (Day 1) and Week 24 and Week 48
measure: Number of Participants With HIV-1 Disease Progression to Stage 3 HIV-associated Conditions, Acquired Immunodeficiency Syndrome (AIDS) or Death (for Participants Under Treatment With DTG + 3TC FDC)
timeFrame: Up to Week 48
measure: Number of Participants Who Completed 24 and 48 Weeks on Study
timeFrame: Week 24 and Week 48
measure: Number of Participants Retained in Care for 24 and 48 Weeks on Study and Have HIV-1 RNA <200 c/mL
timeFrame: Week 24 and Week 48
Other outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 c/mL at Weeks 24 and 48 Among Participants With Available HIV-1 RNA Assessment Regardless of ART
timeFrame: At Week 24 and Week 48
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palm Springs
country: United States
facility: GSK Investigational Site
state: California
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Oakland Park
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Huntersville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Bellaire
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rolle CP, Berhe M, Singh T, Ortiz R, Wurapa A, Ramgopal M, Leone PA, Matthews JE, Dalessandro M, Underwood MR, Angelis K, Wynne BR, Merrill D, Nguyen C, van Wyk J, Zolopa AR. Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV. AIDS. 2021 Oct 1;35(12):1957-1965. doi: 10.1097/QAD.0000000000002979.