A Study to Investigate the Effect of Food on the Bioavailability of a Capsid Inhibitor (CAI) in Male and Female Healthy Participants

HIV Infections Clinical Trial

Official title:

An Open Label, Phase 1 Study to Assess the Effect of Food on Bioavailability for an Investigational Capsid Inhibitor in Healthy Adult Participants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06368986
• Other study ID #: 222420
• Status: Recruiting
• Phase: Phase 1
• Start date: April 17, 2024
• Est. completion date: June 12, 2024

Study information

• Verified date: May 2024
• Source: ViiV Healthcare
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate effect of food (in fasted and fed conditions) on the bioavailability of CAI VH4011499.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: June 12, 2024
• Est. primary completion date: June 12, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

• One SARs-CoV-2 negative test is required prior to dosing (Day -1)

• Body weight within 50-100 kg and body mass index (BMI) within the range 19-32 kg/m2 (inclusive).

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF.

• All participants 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 Human Immunodeficiency Virus (HIV) transmission to an uninfected partner. In addition:

Participants Male at birth: Male participants must agree to use contraception/barrier as detailed below:

• Agree to use a male condom and should also be advised that a female partner (if of child-bearing potential) to use an additional highly effective method of contraception with a failure rate of <1% that has low user dependency or is user dependent through Day 28.

Participants Female at birth: A participant who was female at birth is eligible to participate if they are not pregnant and not breastfeeding. POCBP must be using acceptable forms of birth control through to Day 28. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a POCBP with an early undetected pregnancy. Participants of nonchildbearing potential are also eligible to participate.

Exclusion Criteria:

Medical conditions:

• History or presence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data. The investigator may contact the VH medical monitor to discuss the inclusion of participants who have a history of specific conditions that are not expected to interfere with their participation in the study.

• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).

• Known history of cirrhosis with or without viral hepatitis co-infection.

• History of clinically relevant hepatitis within last 6 months

• Patients with chronic hepatitis B (HBsAg positive) infection

• Abnormal blood pressure as determined by the investigator.

• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

• Breast cancer within the past 10 years.

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).

• QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 msec.

• History of or on-going high-risk behaviors that may put the participant at increased risk for HIV acquisition in the opinion of the investigator. This includes participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.

• Has previously been a participant in another part of study 222420.

• Participants who are breastfeeding or plan to become pregnant during the study.

Prior/concomitant therapy:

• Past or intended use of over-the-counter or prescription medication [including Cytochrome P450 enzyme inducers or inhibitors, vitamins, herbal and dietary supplements (including St. John's Wort)] within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study, unless otherwise specified in protocol or in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.

• Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.

Prior/concurrent clinical study experience:

• Exposure to more than 4 new investigational products within 12 months prior to the first dosing day.

• Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, human blood product, monoclonal antibody, vaccine, invasive device) was administered within 90 days prior to screening or 5 half-lives (whichever is longer). This includes excluding a participant for exposure to an experimental drug, human blood product, monoclonal antibody, or vaccine (which does not have emergency, conditional, or standard market authorization) for SARS-CoV-2 within 90 days prior to screening.

• Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) over a 56-day period.

Diagnostic assessments:

• Any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.

• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the screening period to verify a result.

• ALT >1.5x upper limit of normal (ULN). A single repeat test is allowed within a single screening period to determine eligibility.

• Total bilirubin >1.5x ULN (isolated total bilirubin >1.5x ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%). A single repeat test is allowed within a single screening period to determine eligibility.

• Estimated serum creatinine clearance (using CKD-EPI 2021 eGFRcr) <60 mL/min/1.73 m2.

• History of or current infection with hepatitis B or hepatitis C.

• Positive SARS-CoV-2 test, having signs and symptoms which in the opinion of the investigator are suggestive of COVID-19 (i.e., fever, cough, etc.) within 14 days of inpatient admission, or having contact with known COVID-19 positive person/s in the 14 days prior to inpatient admission.

• Positive pre-study drug/alcohol screen, including tetrahydrocannabinol.

• Positive HIV1&2 antibody test (4th generation Ab/Ag).

• Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

Other exclusions:

• Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units for males or >7 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

• Regular use of known drugs of abuse.

• Sensitivity to the study intervention, or components thereof, or drug or other allergy that, in the opinion of the investigator or VH medical monitor, contraindicates participation in the study.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• VH4011499
VH4011499 administered in fasted or fed conditions.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration - time curve from time zero (pre-dose) to infinity time (AUC[0-inf]) of VH4011499		From Day 1 (pre-dose) to Day 28
Primary	Area under the plasma drug concentration - time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-tlast) of VH4011499		From Day 1 (pre-dose) to Day 28
Primary	Maximum observed plasma drug concentration (Cmax) of VH4011499		From Day 1 (pre-dose) to Day 28
Primary	Time to maximum observed plasma concentration (Tmax) of VH4011499		From Day 1 (pre-dose) to Day 28
Secondary	Number of participants with AEs (Adverse Events), by severity	An AE is any untoward medical occurrence in a participant or clinical investigation participant and can be any sign, symptom, or disease temporally associated with the use of a medicinal product. The severity scale is assessed as following: Grade 1 = mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Grade 2 = moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Grade 3 = severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4 = potentially life-threatening symptoms causing inability to perform self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death, Grade 5 = death.	From Day 1 (pre-dose) to Day 28
Secondary	Number of participants with maximum toxicity grade increase from baseline for liver laboratory parameters	The assessed laboratory assessments include Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct bilirubin and total bilirubin, in both fed and fasted conditions.	From Day 1 (pre-dose) to Day 28
Secondary	Change from baseline in liver panel parameters: total bilirubin and direct bilirubin (micromoles per liter)		From Day 1 (pre-dose) to Day 28
Secondary	Change from baseline in liver panel parameters: ALT, ALP and AST (International units per liter)		From Day 1 (pre-dose) to Day 28