| 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.
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