A Short Term Clinical Study to Evaluate the Anti-HIV Properties and Safety of GSK3640254 in HIV Infected Adults

Phase 1

Conditions: Treatment of human immunodeficiency virus-1 (HIV-1)
MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2018-002208-15-FR

Lead Sponsor: ViiV Healthcare UK Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 34

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2.Participants who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.
3.Screening CD4+ T-cell count =350 cells/mm3
4.Documented HIV infection and Screening plasma HIV-1 RNA =5000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility.
5.Treatment-naïve: No ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
Weight
6.Body weight =50.0 kg (110 lbs.) for men and =45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
Sex
7.Male or female:
a.Male participants:
A male participant with a female partner of child-bearing potential or who is breastfeeding or pregnant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment phase and for at least 14 weeks following the last dose (corresponding to the time needed to eliminate study treatment for potential genotoxic and teratogenic study treatments plus an additional 90 days [spermatogenesis cycle]). In addition, male participants must refrain from donating sperm during this period.
b.Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 5 of protocol ), not breastfeeding, and not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of protocol.
Informed Consent
8.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and stated in the protocol.
Other
9.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 34
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment
2.Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment AND positive on reflex to Hepatitis C RNA
•NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C RNA test is obtained (central lab will automatically reflex to HCV RNA on positive HCVAb)
3.Alanine aminotransferase (ALT) >2 x upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
4.Bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
5.Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones);
6.A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study treatment.
7.Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
8.Any Grade 2-4 laboratory abnormality at Screen, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any lab abnormality is allowed within a single Screening period to determine eligibility.
9.Any pre-existing physical or psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (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.
10.Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Prior/Concomitant Therapy
11.History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
Prior/Concurrent Clinical Study Experience
12.The participant has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study.
Diagnostic assessments
13.Any positive (abnormal) response confirmed by the investigator on a Screening clinician- (or qualified designee-) administered C-SSRS.
14.Any positive result for illicit drug use (e.g., cocaine

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate the antiviral activity of GSK3640254 in HIV-1-infected participants during 10 days of monotherapy;<br> Secondary Objective: •To assess the safety and tolerability of GSK3640254 when administered as monotherapy over 10 days in HIV-1 infected participants<br> •To characterize the pharmacokinetics of GSK3640254 dosing for 10 days in HIV-1 infected patients <br> •To explore the relationship between GSK3640254 exposure and change in plasma HIV-1 RNA<br> •To estimate GSK3640254 accumulation following administration of GSK3640254 for 10 days in HIV-1 infected patients.<br> •To examine dose proportionality of GSK3640254 PK parameters following dosing for 10 days<br> ;Primary end point(s): Maximum change from baseline (Day 1) in plasma HIV-1 ribonucleic acid (RNA);Timepoint(s) of evaluation of this end point: 11 days

Secondary Outcome Measures

Name	Time	Method

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