Human Immunodeficiency Virus-1 infection MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: GSK3515864
Product Code: DTC/3TC Bilayer Tablets, 50 mg/300 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DOLUTEGRAVIR
CAS Number: 1051375-19-9
Current Sponsor code: G
Sponsors
ViiV Healthcare UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 49
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks in virologically suppressed adults living with HIV-1;Secondary Objective: To demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks To evaluate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks To evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR To evaluate the safety and tolerability of DTG/3TC FDC once daily compared to CAR over time To evaluate the safety and tolerability of DTG/3TC FDC once daily in those with creatinine clearance of between 30-49 mL/min/1.73m2 compared to those with a creatinine clearance of =50 mL/min/1.73m2 To evaluate the effects of DTG/3TC FDC once daily on fasting lipids over time compared to CAR To assess viral resistance in participants meeting Confirmed Virologic Withdrawal (CVW) Criteria To assess health related quality of life for participants treated with DTG/3TC FDC compared to CAR;Primary end point(s): Virologic failure endpoint as per FDA snapshot category at Week 48;Timepoint(s) of evaluation of this end point: week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the Snapshot algorithm for the ITT-E population - Virologic failure endpoint as per FDA snapshot category at Week 24 - Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24 using the Snapshot algorithm for the ITT-E population - Change from Baseline in CD4+ cell count and in CD4+/CD8+ cell counts ratio at Weeks 24 and 48 - Incidence of disease progression (HIVassociated conditions, AIDS, and death) through Weeks 24 and 48 - Incidence and severity of adverse events (AEs) and laboratory abnormalities - Proportion of participants who discontinue treatment due to AEs - Change from Baseline in fasting lipids at Weeks 24 and 48 - Incidence of observed genotypic and phenotypic resistance to ARVs for participants meeting CVW Criteria - Change from Baseline in health status using HIV TSQ and SDM at Weeks 24 and 48 (or Withdrawal from the study) and SDM at Weeks 24, 48 and every 24 weeks during the continuation phase (or Withdrawal from the study);Timepoint(s) of evaluation of this end point: Weeks 24 and 48 | — |
Countries
Argentina, Belgium, Brazil, Canada, China, Denmark, France, Germany, Italy, Mexico, Russian Federation, South Africa, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactProject Manager
PPD
Outcome results
None listed