To determine the efficacy, safety and tolerability of two approved medicines, dolutegravir (DTG) plus lamivudine (3TC) taken together as a single tablet, compared with subjects taking their current antiretroviral therapy regimen (CAR) for the treatment of HIV-1 infected adults in whom the HIV-1 virus is currently suppressed.
- Conditions
- Human Immunodeficiency Virus-1 infectionMedDRA version: 20.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2018-000177-72-SE
- Lead Sponsor
- ViiV Healthcare UK Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 490
1. Aged 18 years or older (or older, if required by local regulatory agencies), at the time of signing the informed consent
2. Adults living with HIV
3. 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.
4. Plasma HIV-1 RNA <50 c/mL at Screening.
5. Must be on uninterrupted current regimen (either the initial or second cART regimen) for at least 3 months prior to Screening.
Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification and must NOT have been done for suspected or established treatment failure. The following switches, if they are the only switches, would not be considered a change in regimen;
a. A switch from a PI boosted with RTV to the same PI boosted with cobicistat is allowed (and vice versa).
b. A switch from lamivudine (3TC) to emtricitabine (FTC) (and vice versa)
c. A switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) (and vice versa).
Acceptable stable cART regimens prior to Screening include 2 NRTIs plus:
- INI (either the initial or second cART regimen)
- NNRTI (either the initial or second cART regimen)
- Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen)
6. Male and Female
a. A female participant is eligible to participate if she is not pregnant [as confirmed by a negative serum human chorionic gonadotrophin test at screen and a negative urine hCG test at Randomization (a local serum hCG test at Randomization is allowed if it can be done, and results obtained, within 24 hours prior to randomization)], not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential
OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment period from 28 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication.
The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.
All participants in the study should be counselled 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.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
7. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
8. Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 441
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 49
1. Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study
2. Any evidence of an active CDC Stage 3 disease, EXCEPT cutaneous Kaposi’s sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/mm3 are NOT exclusionary.
3. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
4. 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).
5. 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 DNA as follows:
- Participants positive for HBsAg are excluded.
- Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
Note: Participants 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. Participants with a documented history of chronic HBV and current undetectable HBV DNA while on a TAF/TDF regimen are excluded.
6. Anticipated need for any HCV therapy during the randomized phase of the study, or anticipated need for HCV therapy with a potential for adverse drug-drug interactions with DTG/3TC.
7. Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Participants who are at least 7 days post
completed treatment are eligible.
8. History or presence of allergy or intolerance to the study interventions or their components or drugs of their class.
9. 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.
10. Participants who in the investigator’s judgment, poses a significant suicidality risk
11. 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.
12. Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication.
13. Use of any regimen consisting of single or dual ART (peri-partum treatment with single dose nevirapine is allowed).
14. Current use of stavudine, didanosine, or nelfinavir
15. Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication
16. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
17. Treatment with any of the following agents within 28 days of Screening (radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant)
18. 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method