Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)

• Status: Active, not recruiting
• Trial end date: 2022-04-28
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the study is to establish if human immunodeficiency virus type 1 (HIV-1) infected adult subjects with current virologic suppression on a ≥3-drug tenofovir alafenamide (TAF) based regimen (TBR) remain suppressed upon switching to a two-drug regimen of dolutegravir (DTG) 50 milligram (mg) + lamivudine (3TC) 300 mg. This study will also provide important information regarding the safety and subject satisfaction with this two-drug regimen. The primary objective of this trial is to demonstrate the non-inferior antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 48 weeks in HIV-1 infected, ART-experienced, virologically suppressed subjects. This study also will characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC compared to TBR through Week 144 and characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC through Week 200.

This will be a 200-week, Phase III, randomized, open-label, active-controlled, multicenter, parallel-group study. The study will include a screening phase (up to 28 days), a randomized early switch phase (Day 1 up to Week 148), a randomized late switch phase (Week 148 up to Week 200), and a continuation phase (post Week 200). Approximately 550 HIV-1 infected adults on stable TBR will be randomized 1:1 to switch to DTG + 3TC once daily for up to 200 weeks, or to continue their TBR for 148 weeks, at which time and if HIV-1 ribonucleic acid (RNA) <50 copies per milliliter (c/mL) at Week 144, these subjects will switch to DTG + 3TC up to Week 200.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ViiV Healthcare
• Collaborator: GlaxoSmithKline
• Treatments: Dolutegravir; Lamivudine

Criteria

Inclusion Criteria:

• Subject must be able to understand and comply with protocol requirements, instructions, and restrictions;

• Subject must be likely to complete the study as planned;

• Subject must be considered an appropriate candidate for participation in an investigative clinical trial with medication (e.g. no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country).

• Aged 18 years or older (older where required by local regulatory agencies), at the time of signing the informed consent.

• HIV-1 infected men or women.

• Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.

• Plasma HIV-1 RNA <50 c/mL at Screening.

• Must be on uninterrupted ART for at least 6 months prior to screening. Only the following regimens are allowed:

• Subject on a TAF-based regimen for at least 6 months, or

• Subjects who switched from tenofovir disoproxil fumarate (TDF) (as part of first-line regimen) to tenofovir alafenamide (TAF), without any changes to the other drugs in their regimen, and have been on the TAF-based regimen for at least 3 months immediately prior to Screening. The switch must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for suspected or established treatment failure.

• A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at randomization), not lactating, and at least one of the following conditions applies:

a. Non-reproductive potential defined as:

• Pre-menopausal females with one of the following:

• Documented tubal ligation

• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion

• Hysterectomy

• Documented bilateral oophorectomy

• Post-menopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

b. Reproductive potential and agrees to follow highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) from 30 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication.

• The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. All subjects participating in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions of the consent form and the protocol. Eligible subjects or their legal guardians must sign a written informed consent form before any protocol-specified assessments are conducted.

Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

• Women who are breastfeeding or plan to become pregnant or breastfeed during the study.

• Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease, EXCEPT cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/millimeter (mm)^3 are NOT exclusionary.

• Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.

• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: subjects positive for HBsAg are excluded; subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.

Note: Subjects positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Anti-HBc must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and NOT anti-HBc IgM.

• Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study, for HCV therapy based on interferon or for any drugs that have a potential for adverse drug-drug interactions with study treatment throughout the entire study period.

• Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Subjects who are at least 7 days post completed treatment are eligible.

• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.

• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.

• Subjects who in the investigator's judgment, poses a significant suicidality risk.

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

• Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any systemic immune suppressant.

• 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 investigational product (IP).

• Use of any regimen consisting of single or dual ART.

• Any evidence of major nucleoside reverse transcriptase inhibitor (NRTI) mutation or presence of any major INSTI resistance-associated mutation in any available prior resistance genotype assay test result, if known.

• Any verified Grade 4 laboratory abnormality.

• Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3 times ULN and bilirubin ≥1.5 times ULN (with >35% direct bilirubin).

• Creatinine clearance of <50 mL/minute/1.73 meter^2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method.

• Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.

• Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements ≥50 c/mL.

• Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement ≥50 c/mL.

• Any drug holiday during the 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.

• Any history of switch to another regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA ≥400 c/mL.

• Subjects enrolled in France (or in other countries as required by local regulations or Ethics Committee/Institutional Review Board [IRB]) who:

• Participated in any study using an investigational drug or vaccine during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study, or

• Participate simultaneously in another clinical study.