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
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DOLUTEGRAVIR
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572A
Other descriptive name: DTG
Concentration
Sponsors
ViiV Healthcare UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 years or older (or older where required by local regulatory agencies), at the time of signing the informed consent. 2. HIV-1 infected men or women. 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 ART for at least 6 months prior to screening. Only the following regimens are allowed: a. Subjects on a TAF-based regimen for at least 6 months as the initial regimen, or b. Subjects who switched from a TDF first regimen to 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, i.e., the only switch made is from TDF to TAF. This 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 switch from a PI boosted with RTV to the same PI boosted with cobicistat is allowed (and vice versa). 6. Male or Female 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 (a local serum hCG test at Randomization is allowed if it can be done, and results obtained, within 24 hours prior to 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: o Documented tubal ligation o Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion o Hysterectomy o 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 (refer to laboratory reference ranges for confirmatory levels)]. 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 one of the options listed in the Modified List of 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. 7. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible subjects or their legal guardians must sign a written Informed Consent Form before any protocol-specified assessments are conducted. 8. Subjects enrolled in France must be affiliated to, or a beneficiary o
Exclusion criteria
Exclusion criteria: 1. Women who are breastfeeding or plan to become pregnant or breastfeed during the study. 2. Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], EXCEPT cutaneous Kaposi’s sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/mm3 are NOT exclusionary. 3. Subjects 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: -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. 6. Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study, or anticipated need 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. 7. 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. 8. History or presence of allergy or intolerance to the study drugs 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. Subjects who in the investigator’s judgment, poses a significant suicidality risk. 11. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening; 12. Treatment with any of the following agents within 28 days of Screening -radiation therapy -cytotoxic chemotherapeutic agents -any systemic immune suppressant 13. 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 IP. 14. Use of any regimen consisting of single or dual ART. 15. Any evidence of major NRTI mutation or presence of any major INSTI resistance-associated mutation in any available prior resistance genotype assay test result, if known, must be provided to ViiV after screening and before randomization for review by ViiV Virology. 16. Any verified Grade 4 laboratory abnormality. 17. Alanine aminotransferase (ALT) =5 times the upper limit of normal (ULN) or ALT =3xULN and bilirubin =1.5xULN (with >35% direct bilirubin). 18. Creatinine clearance of 200 c/mL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 therapy (ART)-experienced, virologically suppressed subjects.;Secondary Objective: To demonstrate the antiviral activity of switching to DTG+3TC once daily compared to continuation of TBR over 48 weeks. To demonstrate the antiviral activity of switching to DTG+3TC once daily compared to continuation of TBR over 24 weeks, 96 weeks and 144 weeks. To evaluate the immune effects of DTG+3TC once daily compared to continuation of TBR over 24, 48, 96 and 144 weeks. To evaluate the safety and tolerability of DTG+3TC once daily compared to TBR over time. To evaluate the effects of DTG+3TC once daily on fasting lipids over time compared to TBR. To assess viral resistance in subjects meeting Virologic Withdrawal Criteria. To evaluate renal (in urine and blood) and bone (in blood) biomarkers in subjects treated with DTG+3TC compared to TBR. To assess health related quality of life for subjects treated with DTG+3TC compared to TBR.;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): 1) Proportion of subjects with plasma HIV-1 RNA <50 copies c/mL at Week 48 using the Snapshot algorithm for the ITT-E population 2) Virologic failure endpoint as per FDA snapshot category at Weeks 24, 96 and 144; Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Weeks 24, 96 and 144 using the Snapshot algorithm for the ITT-E population 3) Change from Baseline in CD4+ cell count and in CD4+/CD8+ cell counts ratio at weeks 48, 96 and 144; Incidence of disease progression (HIV-associated conditions, AIDS, and death) through Weeks 24, 48, 96, and 144 4) Incidence and severity of AEs and laboratory abnormalities through 144 weeks; Proportion of subjects who discontinue treatment due to AEs through 144 weeks 5) Change from Baseline in fasting lipids at weeks 24, 48, 96 and 144 6) Incidence of observed genotypic and phenotypic resistance to ARVs for subjects meeting Virologic withdrawal Criteria 7) Change from Baseline in renal and bone biomarkers at Weeks 24, 48, 96 and 144 8) Change from Baseline in health status using EQ-5D-5L at Weeks 24, 48, 96 and 144 (or Withdrawal from the study);Timepoint(s) of evaluation of this end point: 1) 48 weeks 2) 24, 96 and 144 weeks 3) 24, 48, 96 and 144 weeks 4) 144 weeks 5) 24, 48, 96 and 144 weeks 6) During study when event occurred 7) 24, 48, 96 and 144 weeks 8) 24, 48, 96 and 144 weeks (or withdrawal from the study) | — |
Countries
Australia, Belgium, Canada, France, Germany, Japan, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactSR PROJECT MGMT
PPD
Outcome results
None listed