Human Immunodeficiency Virus Type-1 (HIV-1) MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: GSK3640254 (25mg)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not available
CAS Number: 1818867-24-1
Current Sponsor code: GSK3640254
Other descriptive name: GSK3640254D
Sponsors
ViiV Healthcare UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Participants must be 18 years of age inclusive, at the time of signing the informed consent. -Treatment-naïve, defined as no ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection (e.g., use of PreP meets inclusion); -Documented HIV infection and Screening plasma HIV-1 RNA =1000 copies/mL; -Screening CD4+ T-cell count =250 cells/mm3; -Antiviral susceptibility to the NRTI backbone selected should be demonstrated -Body weight =50.0 kg (110 lbs.) for men and =45.0 kg (99 lbs) for women and body mass index (BMI) > 18.5 kg/m2. Calculations will utilize sex assigned at birth. -Participants who are male at birth and participants who are female at birth a. Participants who are female at birth Contraceptive use by participants who are female at birth should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A participant who is female at birth is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies: - Is a participant of non-childbearing potential (PONCBP) as defined in Section 10.4, Contraceptive and Barrier Guidance; OR - Is a POCBP (as defined in Section 10.4) and using an acceptable contraceptive method as described in Section 10.4.2 during the study intervention period (at a minimum until after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention. -If a hormonal method is selected, the participant is required to be clinically stable on it for at least one month prior to starting treatment in the study. -A POCBP must have a negative highly sensitive serum pregnancy test 42 days before the first dose of study intervention. See Section 8.2.5 Pregnancy Testing. -Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.5. -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. -Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. -For participants enrolled in France: a participant will be eligible for inclusion in this study only if either 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 135 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. 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; 2. 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; Note: Other localized malignancies require agreement between the investigator and the ViiV Medical Monitor for inclusion. 3. Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion; 4. Known history of liver cirrhosis with or without viral hepatitis co-infection; 5. Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment) 6. History of ongoing or clinically relevant hepatitis within the previous 6 months; 7. History of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation; 8. Any history of significant underlying psychiatric disorder, in the opinion of the Investigator or ViiV Medical Monitor, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder; or a clinical assessment of suicidality based on the responses on the eCSSRS; 9. Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment; Note: Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor. 10. Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the Investigator or ViiV Medical Monitor (with or without psychiatric evaluation), could interfere with the participant’s ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant; 11. A pre-existing condition, in the opinion of the Investigator or ViiV Medical Monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, or with the absorption, metabolism, and/or excretion of the study drugs or render the participant unable to take oral study treatment; 12. Myocardial infarction in the past 3 months; 13. Familial or personal history of long QT syndrome or sudden cardiac death; 14. Medical history, current or historical, of significant cardiac arrhythmias or ECG findings which, in the opinion of the Investigator or ViiV Medical Monitor, will interfere with the safety
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate antiviral efficacy of GSK3640254 relative to DTG, each given in combination with 2 NRTIs, enabling the selection of an optimal dose for GSK3640254;Secondary Objective: -To evaluate antiviral efficacy in the Randomised Phase of GSK3640254 relative to DTG, each given in combination with 2 NRTIs at Week 48 -To evaluate antiviral efficacy in the Non-Randomised Phase of GSK3640254 optimal dose given in combination with DTG relative to the reference arm (DTG given in combination with 2 NRTIs) at Week 96 -To evaluate safety and tolerability in the Randomised Phase of GSK3640254 relative to DTG, each given in combination with 2 NRTIs at Weeks 24 and 48 -To evaluate antiviral efficacy in the Non- Randomised Phase of GSK3640254 optimal dose given in combination with DTG relative to the reference arm (DTG given in combination with 2 NRTIs) at Week 96 -To assess the development of viral resistance in the Randomised Phase to GSK3640254 and 2 NRTI backbone in participants experiencing virologic failure at Weeks 24 and 48. A complete list of Secondary Objectives can be found on p10 of the protocol;Primary end point(s): Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 24 using the FDA snapshot algorithm;Timepoint(s) of evaluation of this end point: 24 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 48 and 96 using the FDA snapshot algorithm -Absolute values and changes from baseline in HIV-1 RNA through Weeks 24, 48, and 96 -Absolute values and changes from baseline in CD4+ cell counts through Weeks 24, 48, and 96 -Frequency of SAEs, Deaths and AEs leading to Discontinuation through Weeks 24, 48, and 96 -Incidence and severity of AEs through Weeks 24, 48 and 96 -AEs in GI, Psych/CNS through Weeks 24, 48 and 96 -Changes in genotypic and/or phenotypic profiles of virus compared to baseline through Weeks 24, 48, and 96 -The steady-state plasma PK parameters of GSK3640254 will be assessed based on Intensive and/or Sparse PK sampling through Weeks 24 and 48;Timepoint(s) of evaluation of this end point: Week 24, 48, 96 | — |
Countries
Argentina, Canada, France, Germany, Italy, Portugal, Russian Federation, South Africa, Spain, Switzerland, United States
Contacts
Public ContactGSK Clinical Support HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed