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

HIV Infections Clinical Trial

— SPAN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05291520
• Other study ID #: 217901
• Status: Completed
• Phase: Phase 1
• Start date: February 23, 2022
• Est. completion date: April 10, 2023

Study information

• Verified date: May 2023
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 10, 2023
• Est. primary completion date: April 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ENHANZE™ Drug Product (EDP)

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• VH3810109
VH3810109 will be administered.
• rHuPH20
rHuPH20 will be administered.

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	Percentage of participants with = Grade 2 adverse events (AEs) following SC administration of VH3810109	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 will be used for all AE severity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening. The higher the grade, the more severe the symptoms.	Up to Week 24
Primary	Percentage of participants with = Grade 2 AEs following IV administration of VH3810109	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 will be used for all AE severity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening. The higher the grade, the more severe the symptoms.	Up to Week 24
Primary	Percentage of participants with serious adverse events (SAE) following VH3810109 SC administration	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, other situations as judged by physician.	Up to Week 24
Primary	Percentage of participants with SAE following VH3810109 IV administration	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, other situations as judged by physician.	Up to Week 24
Primary	Percentage of participants with injection site reactions (ISRs) following VH3810109 SC administration	ISRs will be recorded via ISR diaries and managed through investigator assessment. Percentage of participants who experience any injection site reaction (like pain, itching, bruising, bump, discoloration, redness, skin firmness, swelling, warm to touch etc.) will be reported.	Up to 7 days
Primary	Percentage of participants with ISRs following VH3810109 IV administration	ISRs will be recorded via ISR diaries and managed through investigator assessment. Number of participants who experienced any injection site reaction (like pain, itching, bruising, bump, discoloration, redness, skin firmness, swelling, warm to touch etc.) will be reported.	Up to 7 days
Primary	Percentage of participants with Grade 2 to 4 elevated alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) values following VH3810109 SC administration	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
Primary	Percentage of participants with Grade 2 to 4 elevated ALT/AST values following VH3810109 IV administration	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	Part 1 and Part 2: Area under the plasma concentration-time curve (AUC) from time zero extrapolated to infinity (AUC[0-inf]) of VH3810109	Blood samples will be collected at the indicated time points for PK analysis of VH3810109	Up to Week 24
Secondary	Part 1 and Part 2: AUC from time zero to time t (AUC[0-t]) of VH3810109	Blood samples will be collected at the indicated time points for PK analysis of VH3810109	Up to Week 24
Secondary	Part 1 and Part 2: Maximum observed concentration (Cmax) of VH3810109	Blood samples will be collected at the indicated time points for PK analysis of VH3810109	Up to Week 24
Secondary	Part 1 and Part 2: Time of maximum observed concentration (Tmax) of VH3810109	Blood samples will be collected at the indicated time points for pharmacokinetic analysis of VH3810109	Up to Week 24
Secondary	Part 1 and Part 2: Apparent terminal phase half-life (t1/2) of VH3810109	Blood samples will be collected at the indicated time points for PK analysis of VH3810109	Up to Week 24
Secondary	Number of participants with change in dimension score "acceptance of ISRs" using Perception of Injection (PIN) Questionnaire	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. Dimension scores include bother from ISR, leg movement, sleep and acceptability. Score of a dimension is calculated as mean of all items with dimension. Higher scores represent worse perception of injection.	Day 2 and Day 7
Secondary	Number of participants with Individual item score assessing pain using PIN Questionnaire	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. These items in the scale are rated on a 5-point scale ranging from 1(very dissatisfied, extremely, etc.) to 5 (very satisfied, not at all, etc.). Lower scores represent worse perception of injection.	Day 2 and Day 7
Secondary	Percentage of participants reporting being bothered or affected by the pain and local reactions based on the PIN Questionnaire	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.	Day 2 and Day 7
Secondary	Percentage of participants with post-injection pain assessment using Numeric Rating Scale (NRS) following VH3810109 SC administration	Post-injection assessment of score will be measured based on NRS which is a 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain).	Day 1, 2 and 7
Secondary	Percentage of participants with post-injection pain assessment using NRS following VH3810109 IV administration	Post-injection assessment of score will be measured based on NRS which is a 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain).	Day 1, 2 and 7
Secondary	Percentage of participants reporting ISRs overall and by grade	ISRs will be recorded via ISR diaries and managed through investigator assessment. Severity of injection site reactions was analyzed using DAIDS AE Grading Table. The severity is 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. Higher grade indicates more severe condition.	Up to Day 14
Secondary	Duration of ISRs overall and by grade	ISRs will be recorded via ISR diaries and managed through investigator assessment.	Up to Day 14
Secondary	Change from baseline in Platelets, WBC count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils (cells per microliter)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Hematocrit (percentage)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Hgb, albumin and total protein (grams per deciliter)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Red Blood Cell Count (RBC) (million cells per microliter)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Mean Corpuscle Volume (MCV) (cubic microns)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Mean Corpuscle Hemoglobin (MCH) (picograms per cell)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (percentage)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Glucose (fasting), BUN, Creatinine, Direct Bilirubin and Total Bilirubin (milligrams per deciliter)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Sodium, Potassium, Calcium, Chloride and Carbon Dioxide (milliequivalents per liter)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and alkaline phosphatase (ALP) (International Units per liter)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in urine Specific Gravity (ratio)		Baseline (Day -1) to Week 24
Secondary	Number of participants with presence of Glucose, Protein, Blood, Ketones, Bilirubin, Urobilinogen, Nitrite, Leukocyte Esterase in urine	Urine samples will be collected to analyse presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase in urine.	Baseline (Day -1) to Week 24
Secondary	Urine Potential of Hydrogen (pH) Analysis by Dipstick Method	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).	Baseline (Day -1) to Week 24
Secondary	Change from baseline in PR Interval, QRS Interval, QT Interval, and QT Interval corrected for heart rate using Fridericia's formula (QTcF)		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Temperature		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Pulse Rate		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Respiratory Rate		Baseline (Day -1) to Week 24
Secondary	Change from baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)		Baseline (Day -1) to Week 24