A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of VH3810109 (Also Known as GSK3810109), Administered Either Subcutaneously (SC) With rHuPH20 or Intravenously (IV), in Healthy Adult Participants (SPAN)

A Phase 1, Open-Label, Single-Dose Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either Subcutaneously or Intravenously With Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

An open-label, two part study to assess the safety, tolerability, and PK of VH3810109 in healthy adult participants. Participants will receive a single SC or IV dose of VH3810109 co-administered with rHuPH20 and will be followed up for 24 weeks.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: VH3810109; Biological: rHuPH20

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and without history of any of the conditions listed in the exclusion criteria.
• Participants having body weight of ≥50 kilogram (kg) and <100 kg
• Participants having a clinical laboratory profile within the normal range or must have results that do not show clinically significant abnormalities, as judged by the investigator at screening.
• Contraceptive use by men or women participants 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 applies:

Is not a participant of childbearing potential (POCBP) or Is a POCBP and agree to use an acceptable contraceptive method as described in Section 10.4 from 3 weeks prior to the start of this study and during the study. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.

A POCBP must have a negative highly sensitive serum pregnancy test on Day -1, prior to the first dose of study intervention 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).

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.

• Capable of giving written informed consent.

Exclusion Criteria:

• Hypertension that is not well controlled.
• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological 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.
• Positive human immunodeficiency virus (HIV) antibody test.
• Positive test result for SARS-CoV-2.
• Evidence of hepatitis B (HB) virus infection at screening or within 3 months prior to first dose of study intervention Participants positive for Hepatitis B antigen (HBsAg) are excluded. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for Hepatitis B virus (HBV) DNA are excluded
• 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 (i.e., infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) or tattoos that would interfere with assessment of injection sites.
• 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 that, in the opinion of the investigator or medical monitor, contraindicates their participation.
• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A, dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
• 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.
• Prior receipt of licensed or investigational Monoclonal antibody (Mab).
• Receipt of any investigational study agent within 28 days prior to first dose of study treatment
• Prior exposure to VH3810109 or rHuPH20 in this or another clinical study.
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• ALT ≥1.5 times the upper limit of normal (ULN).
• Total bilirubin ≥1.5 times the ULN (isolated total bilirubin >1.5×ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%).
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Corrected QT interval Fridericia's formula (QTcF)>450 millisecond (msec) for males and QTcF >470 msec for females.
• The participant has a tattoo or other dermatological condition overlying potential injection sites that may interfere with interpretation of ISRs or administration of VH3810109.
• Grade 4 laboratory abnormalities.
• Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the subject including (but not limited to): diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of drug or alcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.
• Known hypersensitivity to hyaluronidase or any of the excipients in ENHANZ Drug Product (EDP)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Group: VH3810109 20 mg/kg + rHuPH20 [SC]; Participants in this group received a single subcutaneous (SC) dose of VH3810109 20 mg/kg co-administered with rHuPH20 at Day 1 and were followed up to 24 weeks.	Biological: VH3810109; VH3810109 was administered.; Biological: rHuPH20; rHuPH20 was administered.
Experimental: Part 2 Group: VH3810109 60 mg/kg [IV]; Participants in this group received a single intravenous (IV) dose of VH3810109 60 mg/kg at Day 1 and were followed up to 24 weeks.	Biological: VH3810109; VH3810109 was administered.
Experimental: Part 3 Group: VH3810109 3000 mg + rHuPH20 [SC]; Participants in this group received a single subcutaneous (SC) dose of VH3810109 3000 mg co-administered with rHuPH20 at Day 1 and were followed up to 24 weeks.	Biological: VH3810109; VH3810109 was administered.; Biological: rHuPH20; rHuPH20 was administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Grade 2 or Higher (>=) Adverse Events (AEs) Following SC Administration of VH3810109 (Part 1 and Part 3)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening. This outcome measure is presenting only data for Grade 2 or more of severity.	Up to Week 24
Number of Participants With Serious Adverse Events (SAEs) Following SC Administration of VH3810109 (Part 1 and Part 3)	An SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or other situations as judged by physician.	Up to Week 24
Number of Participants With Injection Site Reactions (ISRs) Following VH3810109 SC Administration (Part 1 and 3)	ISRs were recorded via ISR diaries and managed through investigator assessment. The participants who experienced any injection site reaction were reported.	Up to 7 days post-dose
Number of Participants With Grade 2 to 4 Elevated Alanin Aminotransferase/Aspartate Aminotransferase (ALT/AST) Values Following VH3810109 SC Administration (Part 1 and 3)	Liver chemistry stopping and increased monitoring criteria is analyzed using DAIDS AE Grading Table, where Grade 2 (moderate): causing greater than minimal interference with usual social and functional activities, Grade 3 (severe): causing inability to perform usual social and functional activities, Grade 4 (Potentially life threatening): causing inability to perform basic self-care functions or hospitalization indicated.	Up to Week 24
Number of Participants With >= Grade 2 AEs Following IV Administration of VH3810109 (Part 2)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening. This outcome measure is presenting only data for Grade 2 or more of severity.	Up to Week 24
Number of Participants With SAEs Following IV Administration of VH3810109 (Part 2)	An SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or other situations as judged by physician.	Up to Week 24
Number of Participants With Grade 2 to 4 Elevated ALT/AST Values Following VH3810109 IV Administration (Part 2)	Liver chemistry stopping and increased monitoring criteria is analyzed using DAIDS AE Grading Table, where Grade 2 (moderate): causing greater than minimal interference with usual social and functional activities, Grade 3 (severe): causing inability to perform usual social and functional activities, Grade 4 (Potentially life threatening): causing inability to perform basic self-care functions or hospitalization indicated.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) of VH3810109	Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis of VH3810109.	Up to Week 24
AUC From Time Zero to Time t (AUC[0-t]) of VH3810109	Blood samples were collected as assessed by protocol, at specific time points for PK analysis of VH3810109.	Up to Week 24
Maximum Observed Concentration (Cmax) of VH3810109	Blood samples were collected as assessed by protocol, at specific time points for PK analysis of VH3810109.	Up to Week 24
Time of Maximum Observed Concentration (Tmax) of VH3810109	Blood samples were collected as assessed by protocol, at specific time points for PK analysis of VH3810109.	Up to Week 24
Apparent Terminal Phase Half-life (t1/2) of VH3810109	Blood samples were collected as assessed by protocol, at specific time points for PK analysis of VH3810109.	Up to Week 24
Score Recorded for "Acceptance of ISRs", Using Perception of Injection (PIN) Questionnaire (Part 1 and 3)	The PIN questionnaire measure contains 21 items: pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside clinical trial. Scores range from 1 to 5; questions are phrased to ensure that 1: most favorable perception of vaccination, and 5: most unfavorable. Score of a dimension is calculated as mean of all items with dimension. Higher scores represent worse perception of injection.	At Day 2 and Day 7
Number of Participants Reporting Pain, Using Perception of Injection (PIN) Questionnaire (Part 1 and 3)	The PIN questionnaire measure contains 21 items: pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside clinical trial. Scores range from 1 to 5; the scores are defined as following: 1=not at all bothered, 2=a little bothered, 3=moderately bothered, 4=very bothered, 5=extremely bothered; questions are phrased to ensure that 1: most favorable perception of vaccination, and 5: most unfavorable. Score of a dimension is calculated as mean of all items with dimension. Higher scores represent worse perception of injection.	At Day 2 and Day 7
Number of Participants Reporting Being Bothered or Affected by the Pain and Local Reactions Based on the PIN Questionaire (Part 1 and 3)	The PIN questionnaire measure contains 21 items: pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside clinical trial. Scores range from 1 to 5; the scores are defind as following: 1=totaly acceptable, 2=very acceptable, 3=moderately acceptable, 4=a little acceptable, 5=not at all acceptable; questions are phrased to ensure that 1: most favorable perception of vaccination, and 5: most unfavorable. Score of a dimension is calculated as mean of all items with dimension. Higher scores represent worse perception of injection.	At Day 2 and Day 7
Score Reported for Post-injection Pain Assessment Using Numeric Rating Scale (NRS) Following VH3810109 SC Administration (Part 1 and 3)	Post-injection assessment of pain was measured based on NRS which is a 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).	At Day 1, Day 2 and Day 7
Scores Reported for Post-injection Pain Assessment Using Numeric Rating Scale (NRS) Following VH3810109 IV Administration (Part 2)	Post-injection assessment of pain was measured based on NRS which is a 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).	At Day 1, Day 2 and Day 7
Number of ISRs Events Overall and by Grade (Part 1 and 3)	ISRs were recorded via ISR diaries and managed through investigator assessment. Severity of injection site reactions was analyzed using DAIDS AE Grading Table. The severity was categorized into grades as following: Grade 1 (mild): causing no or minimal interference with usual social and functional activities, Grade 2 (moderate): causing greater than minimal interference with usual social and functional activities, Grade 3 (severe): causing inability to perform usual social and functional activities, Grade 4 (Potentially life threatening): causing inability to perform basic self-care functions or hospitalization indicated, Grade 5 (death). Higher grade indicates more severe condition.	Up to day 14
The Overall Duration of ISRs, Expressed in Days	ISRs will be recorded via ISR diaries and managed through investigator assessment.	From Day 1 up to Day 14
Change From Baseline in Platelets, White Blood Cells (WBC), Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Hematocrit	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Hemoglobin, Albumin and Total Protein	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Red Blood Cell Count (RBC)	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Mean Corpuscle Volume (MCV)	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Mean Corpuscle Hemoglobin (MCH)	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Direct Bilirubin and Total Bilirubin	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in Sodium, Potassium, Calcium, Chloride and Carbon Dioxide	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Change From Baseline in ALT, AST and Alkaline Phosphatase (ALP)	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109.	From Baseline (Day -1) up to Week 24
Number of Participants With Worst Case Urinalysis at Post-baseline Compared With Baseline	Urine samples were collected as assessed by protocol, at specific time points for laboratory analysis of VH3810109. At baseline and post-baseline, worst case urinalysis data was determined by comparing the resulted values of the urinalysis for each participant to the normal rage. This endpoint evaluates the changes from baseline for the worst case urinalysis.	Day 14 compared with baseline (Day -1)
Change From Baseline in PR Interval, QRS Interval, QT Interval, and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)	ECG values were collected as assessed by protocol, at the indicated time points.	From Baseline (Day -1) up to Week 24
Change From Baseline in Temperature	Temperature was measured at the indicated time points, in a supine position after the participant has been at rest for at least 5 minutes in a quiet setting without distractions.	From Baseline (Day -1) up to Week 24
Change From Baseline in Pulse Rate	Pulse rate was measured at the indicated time points, in a supine position after the participant has been at rest for at least 5 minutes in a quiet setting without distractions.	From Baseline (Day -1) up to Week 24
Change From Baseline in Respiratory Rate	Respiratory rate was measured at the indicated time points, in a supine position after the participant has been at rest for at least 5 minutes in a quiet setting without distractions.	From Baseline (Day -1) up to Week 24
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Blood pressure was measured at the indicated time points, in a supine position after the participant has been at rest for at least 5 minutes in a quiet setting without distractions.	From Baseline (Day -1) up to Week 24

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Investigators: Study Director: GSK Clinical Trials, ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2022
• Primary Completion (Actual): April 10, 2023
• Study Completion (Actual): April 10, 2023

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Safety; HIV; Pharmacokinetics; Tolerability; Human Monoclonal Antibody; rHuPH20; VH3810109; GSK3810109; N6LS
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections
• Other Study ID Numbers: 217901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No