Clinical trial NCT06652958: A Study to Assess the Safety and Pharmacokinetics of a Human Monoclonal Antibody (VH4527079) in Healthy Adults and Persons With HIV
Official title: A Phase 1, Open-Label, Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VH4527079, Administered Either Intravenously or Subcutaneously to Healthy Adults and Persons With HIV
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HIV Infections
Keywords: Human Immunodeficiency Virus (HIV)
VH4527079
Monoclonal Antibody
Safety
Pharmacokinetics (PK)
Healthy Adults
Persons with HIV (PWH)
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2024-10-22
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study evaluates the safety, tolerability, and pharmacokinetics (PK) of a single dose administration of VH4527079 by subcutaneous (SC) injection or by intravenous (IV) infusion in healthy adult participants and multiple dose administration by IV infusion in healthy adult participants and in Persons with HIV (PWH).


Eligibility criteria: 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 based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
* Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
* For Cohort 9 (PWH in Arm B), well controlled HIV on first-line INSTI-based oral antiretroviral therapy without history of virologic failure (will be continued during study).
* Body weight more than or equal to (\>=)50.0 kg for men and \>=45.0 kg for women and Body Mass Index (BMI) within the range 18.5 to 31.0 kg/m\^2.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  - Participants who are female at birth are eligible to participate if at least one of the following conditions applies: Not pregnant or breastfeeding and, at least, one of the following conditions apply:
  * Is not a Participant of childbearing potential (POCBP). OR
  * Is a POCBP and agrees to use a highly effective contraceptive method 3 weeks prior to the start of this study and during the study.
* Capable of giving signed informed consent.
* Willing to have samples stored for future research for participants in Arm B; Cohort 8 (Healthy Volunteers) and Cohort 9 (PWH in Arm B).

Exclusion Criteria:

* History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders, or any medical condition 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.
* Weight \>115.0 kg.
* Any medical condition that is not well controlled.
* Positive HIV testing for participants enrolled in Arm A and in Arm B Cohort 8.
* Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of recurrence during the study.
* The participant has an underlying skin disease or disorder, piercing, or tattoos that would interfere with assessment of injection site reactions.
* History of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy.
* Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions.
* Any condition which, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to take oral medication.
* Unstable liver disease, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease).
* Known history of cirrhosis with or without viral hepatitis co-infection.
* History of clinically relevant hepatitis within last 6 months.
* For Cohort 9 (PWH in Arm B), untreated syphilis infection (i.e., positive syphilis testing at screening) without documentation of treatment. Participants who have successfully completed treatment at least 7 days previously are eligible if recruitment is open. Positive syphilis testing at screening for any other Cohort is exclusionary.
* Lymphoma, leukemia, or any malignancy (except for breast cancer) 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.
* Participants who poses a significant suicidality risk.
* Any pre-existing physical or mental condition which, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
* Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery or percutaneous transluminal coronary angioplasty or any clinically significant cardiac disease.
* Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome or sudden cardiac death. Any significant arrhythmia or ECG finding which, will interfere with the safety for the individual participant.
* Exposure to an experimental drug, human blood product, anticoagulants, or experimental vaccine (which does not have emergency, conditional, or standard market authorization) within 30 days, or within 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 study intervention or plans to receive live vaccines during the study.
* Any previous use of HIV Pre-exposure prophylaxis (PrEP) or Post-exposure prophylaxis (PEP) in Arm A (Cohorts 1 through 7) or Arm B (Cohort 8 only), either oral or parenteral, is exclusionary.
* Any previous use of Neonatal Fc receptor blockers (e.g., efgartigimod alfa-fcab).
* The participant has ever received an investigational HIV vaccine.
* Any approved or experimental non-HIV vaccination (e.g., SARS-CoV-2, HBV, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment (Day 0).
* Exposure to an experimental drug, human blood product, or vaccine (which does not have emergency, conditional, or standard market authorization) within 28 days prior to the first dose of study treatment or plans to receive live vaccines during the study.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
* Exposure to more than 4 new chemical entities or vaccines within 12 months prior to the first dosing day.
* Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing.
* Participants who require concomitant medications known to be associated with a prolonged QTc.
* Participants receiving any protocol-prohibited medication(s) and who are unwilling or unable to switch to an alternate medication.

Primary outcomes:
measure: Number of participants with adverse events (AEs) of Grade 2 and above severity
timeFrame: Up to Week 24 follow-up period
measure: Area under the plasma-concentration time curve from time zero to infinity (AUC0-inf) of VH4527079
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Area under the plasma-concentration time curve from time zero to the last quantifiable concentration (AUC0-tlast) of VH4527079
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Area under the plasma-concentration time curve from defined interval between doses (AUCtau) of VH4527079
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Maximum observed plasma concentration (Cmax) of VH4527079
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Time to maximum observed plasma concentration (Tmax) of VH4527079
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Apparent terminal half-life (t1/2) of VH4527079
timeFrame: From Day 1 Up to Week 24 follow-up period
Secondary outcomes:
measure: AUC0-inf of VH4527079 after a single dose administered via SC route relative to IV administration
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: AUC0-tlast of VH4527079 after a single dose administered via SC route relative to IV administration
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Cmax of VH4527079 after a single dose administered via SC route relative to IV administration
timeFrame: From Day 1 Up to Week 24 follow-up period
measure: Post-baseline values for chemistry panels: Glucose (fasting), Blood Urea Nitrogen, Creatinine, Calcium, Magnesium, Potassium, Phosphate, Direct Bilirubin, Total Bilirubin and Fasting lipid panel (milligrams per deciliter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for chemistry panels: AST/SGOT, ALT/SGPT, ALP and CPK (International Units per liter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for chemistry panels: Amylase and Lipase (fasting) (Units per Liter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for chemistry panels: Total Protein (Grams per deciliter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for chemistry panels: Sodium chloride and Bicarbonate (milliequivalents per liter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Platelet count (cells per microliter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Red Blood Cell (RBC) Count (million cells per microliter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Hemoglobin (Hgb) (grams per deciliter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Hematocrit (Proportion of red blood cells in blood)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Mean Corpuscular Volume (MCV) (Femtoliters)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Mean Corpuscular Hemoglobin (MCH) (Picograms)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Reticulocytes (Percentage of reticulocytes)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for hematology panels: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for coagulation panels: Prothrombin time (PT) and Partial Thromboplastin Time (PTT) (Seconds)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Post-baseline values for coagulation panels: International normalized ratio (INR) (Ratio)
timeFrame: From Day 1 (pre-Dose 1) Up to Week 24 follow-up period
measure: Change from baseline values for chemistry panels: Glucose (fasting), Blood Urea Nitrogen, Creatinine, Calcium, Magnesium, Potassium, Phosphate, Direct Bilirubin, Total Bilirubin and Fasting lipid panel (milligrams per deciliter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for chemistry panels: AST/ SGOT, ALT/ SGPT, ALP and CPK (International Units per liter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for chemistry panels: Amylase and Lipase (fasting) (Units per Liter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for chemistry panels: Total Protein (Grams per deciliter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for chemistry panels: Sodium chloride and Bicarbonate (milliequivalents per liter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: Platelet count (cells per microliter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: RBC Count (million cells per microliter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: Hgb (grams per deciliter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: Hematocrit (Proportion of red blood cells in blood)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: MCV (Femtoliters)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: MCH (Picograms)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: Reticulocytes (Percentage of reticulocytes)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for hematology panels: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for coagulation panels: PT and PTT (Seconds)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Change from baseline values for coagulation panels: INR (Ratio)
timeFrame: From Day 1 (pre-Dose 1) up to Week 24 follow-up period
measure: Number of participants with maximum post-baseline QT interval corrected (QTc) values compared to baseline by category
timeFrame: Up to Week 24 follow-up period
measure: Number of participants with maximum post-baseline increases in QTc values compared to baseline by category
timeFrame: Up to Week 24 follow-up period
measure: Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline for diastolic and systolic blood pressure
timeFrame: Up to Week 24 follow-up period
measure: Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline for pulse rate
timeFrame: Up to Week 24 follow-up period
measure: Number of participants with any AEs and AEs by severity
timeFrame: Up to Week 24 follow-up period
measure: Number of participants who discontinue treatment due to AEs
timeFrame: Up to Week 24 follow-up period
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
References: