Clinical trial NCT05291520: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: VH3810109
GSK3810109
HIV
Human Monoclonal Antibody
rHuPH20
Pharmacokinetics
Safety
Tolerability
N6LS
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2022-03-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants will receive a single SC or IV dose of VH3810109 co-administered with rHuPH20
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Grade 2 or Higher (>=) Adverse Events (AEs) Following SC Administration of VH3810109 (Part 1 and Part 3)
timeFrame: Up to Week 24
measure: Number of Participants With Serious Adverse Events (SAEs) Following SC Administration of VH3810109 (Part 1 and Part 3)
timeFrame: Up to Week 24
measure: Number of Participants With Injection Site Reactions (ISRs) Following VH3810109 SC Administration (Part 1 and 3)
timeFrame: Up to 7 days post-dose
measure: Number of Participants With Grade 2 to 4 Elevated Alanin Aminotransferase/Aspartate Aminotransferase (ALT/AST) Values Following VH3810109 SC Administration (Part 1 and 3)
timeFrame: Up to Week 24
measure: Number of Participants With >= Grade 2 AEs Following IV Administration of VH3810109 (Part 2)
timeFrame: Up to Week 24
measure: Number of Participants With SAEs Following IV Administration of VH3810109 (Part 2)
timeFrame: Up to Week 24
measure: Number of Participants With Grade 2 to 4 Elevated ALT/AST Values Following VH3810109 IV Administration (Part 2)
timeFrame: Up to Week 24
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) of VH3810109
timeFrame: Up to Week 24
measure: AUC From Time Zero to Time t (AUC[0-t]) of VH3810109
timeFrame: Up to Week 24
measure: Maximum Observed Concentration (Cmax) of VH3810109
timeFrame: Up to Week 24
measure: Time of Maximum Observed Concentration (Tmax) of VH3810109
timeFrame: Up to Week 24
measure: Apparent Terminal Phase Half-life (t1/2) of VH3810109
timeFrame: Up to Week 24
measure: Score Recorded for "Acceptance of ISRs", Using Perception of Injection (PIN) Questionnaire (Part 1 and 3)
timeFrame: At Day 2 and Day 7
measure: Number of Participants Reporting Pain, Using Perception of Injection (PIN) Questionnaire (Part 1 and 3)
timeFrame: At Day 2 and Day 7
measure: Number of Participants Reporting Being Bothered or Affected by the Pain and Local Reactions Based on the PIN Questionaire (Part 1 and 3)
timeFrame: At Day 2 and Day 7
measure: Score Reported for Post-injection Pain Assessment Using Numeric Rating Scale (NRS) Following VH3810109 SC Administration (Part 1 and 3)
timeFrame: At Day 1, Day 2 and Day 7
measure: Scores Reported for Post-injection Pain Assessment Using Numeric Rating Scale (NRS) Following VH3810109 IV Administration (Part 2)
timeFrame: At Day 1, Day 2 and Day 7
measure: Number of ISRs Events Overall and by Grade (Part 1 and 3)
timeFrame: Up to day 14
measure: The Overall Duration of ISRs, Expressed in Days
timeFrame: From Day 1 up to Day 14
measure: Change From Baseline in Platelets, White Blood Cells (WBC), Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Hematocrit
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Hemoglobin, Albumin and Total Protein
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Red Blood Cell Count (RBC)
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Mean Corpuscle Volume (MCV)
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Mean Corpuscle Hemoglobin (MCH)
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Direct Bilirubin and Total Bilirubin
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Sodium, Potassium, Calcium, Chloride and Carbon Dioxide
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in ALT, AST and Alkaline Phosphatase (ALP)
timeFrame: From Baseline (Day -1) up to Week 24
measure: Number of Participants With Worst Case Urinalysis at Post-baseline Compared With Baseline
timeFrame: Day 14 compared with baseline (Day -1)
measure: Change From Baseline in PR Interval, QRS Interval, QT Interval, and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Temperature
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Pulse Rate
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Respiratory Rate
timeFrame: From Baseline (Day -1) up to Week 24
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: From Baseline (Day -1) up to Week 24
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: