HIV-1 infection
Conditions
Interventions
investigational material(s)
Generic name etc : Dolutegravir+Lamivudine Fix Dose Combination
INN of investigational material : Dolutegravir+Lamivudine
Therapeutic category code : 625 Anti-virus agents
Sponsors
ViiV Healthcare
Eligibility
Sex/Gender
All
Inclusion 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 less than 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 less than 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
Exclusion criteria
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 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 or more times the upper limit of normal (ULN) or ALT 3 or more times ULN and bilirubin 1.5 or more times ULN (with more than 35% direct bilirubin). Creatinine clearance of less than 50 mL/minute/1.73 meter2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. Within the 6 to 12 month window prior to Screening and after confirmed suppression to less than 50 c/mL, any plasma HIV-1 RNA measurement more
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Number of subjects with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48 [ Time Frame: Week 48 ] Number of subjects with virologic failure was evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks. Plasma samples for HIV-1 RNA was collected at Week 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy Number of subjects with plasma HIV-1 RNA less than50 c/mL at Week 24 using the Snapshot algorithm [ Time Frame: Week 24 ] Number of subjects with plasma HIV-1 RNA less than50 c/mL at Week 48 using the Snapshot algorithm [ Time Frame: Week 48 ] Number of subjects with plasma HIV-1 RNA less than50 c/mL at Week 96 using the Snapshot algorithm [ Time Frame: Week 96 ] Number of subjects with plasma HIV-1 RNA less than50 c/mL at Week 144 using the Snapshot algorithm [ Time Frame: Week 144 ] Number of subjects with virologic failure endpoint as per FDA snapshot category at Week 24 [ Time Frame: Week 24 ] Number of subjects with virologic failure endpoint as per FDA snapshot category at Week 96 [ Time Frame: Week 96 ] Number of subjects with virologic failure endpoint as per FDA snapshot category at Week 144 [ Time Frame: Week 144 ] Change from Baseline in CD4+ lymphocyte count at Week 24 [ Time Frame: Baseline and Week 24 ] Change from Baseline in CD4+ lymphocyte count at Week 48 [ Time Frame: Baseline and Week 48 ] Change from Baseline in CD4+ lymphocyte count at Week 96 [ Time Frame: Baseline and Week 96 ] Change from Baseline in CD4+ lymphocyte count at Week 144 [ Time Frame: Baseline and Week 144 ] Change from Baseline in CD4+/CD8+ cell count ratio at Week 24 [ Time Frame: Baseline and Week 24 ] Change from Baseline in CD4+/CD8+ cell count ratio at Week 48 [ Time Frame: Baseline and Week 48 ] Change from Baseline in CD4+/CD8+ cell count ratio at Week 96 [ Time Frame: Baseline and Week 96 ] Change from Baseline in CD4+/CD8+ cell count ratio at Week 144 [ Time Frame: Baseline and Week 144 ] Number of subjects with HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death through Week 24 [ Time Frame: Week 24 ] Number of subjects with HIV-associated conditions, AIDS and death through Week 48 [ Time Frame: Week 48 ] Number of subjects with HIV-associated conditions, AIDS and death through Week 96 [ Time Frame: Week 96 ] Number of subjec | — |
Countries
Asia except Japan, Europe, Japan, North America, Oceania
Outcome results
None listed