A Study to Evaluate the Safety and Pharmacokinetics (PK) of VH3810109 (Also Known as GSK3810109), Administered Subcutaneously (SC) With Recombinant Human Hyaluronidase PH20 (rHuPH20) in Healthy Adults
Study Details
Study Description
Brief Summary
An open-label, single-dose study to assess the safety, tolerability, and PK of VH3810109 in healthy adult participants. Participants will receive a single SC dose of VH3810109 co-administered with rHuPH20 and will be followed up for 24 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VH3810109 + rHuPH20 Healthy participants will receive a single SC dose of VH3810109 injection with rHuPH20. |
Biological: VH3810109
VH3810109 will be administered.
Biological: rHuPH20
rHuPH20 will be administered.
|
Outcome Measures
Primary Outcome Measures
- Percentage of participants with ≥ Grade 2 adverse events (AEs) [Up to Week 24]
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.
- Percentage of participants serious adverse events (SAE) [Up to Week 24]
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.
- Percentage of participants with injection site reactions (ISRs) [Up to 7 days]
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 presented.
- Percentage of participants with Grade 2 to 4 alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) values [Up to Week 24]
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.
Secondary Outcome Measures
- Area under the plasma concentration-time curve (AUC) from time zero extrapolated to infinity (AUC[0-inf]) of VH3810109 [Up to Week 24]
Blood samples will be collected at the indicated time points for PK analysis of VH3810109
- AUC from time zero to time t (AUC[0-t]) of VH3810109 [Up to Week 24]
Blood samples will be collected at the indicated time points for PK analysis of VH3810109
- Maximum observed concentration (Cmax) of VH3810109 [Up to Week 24]
Blood samples will be collected at the indicated time points for PK analysis of VH3810109
- Time of maximum observed concentration (Tmax) of VH3810109 [Up to Week 24]
Blood samples will be collected at the indicated time points for pharmacokinetic analysis of VH3810109
- Apparent terminal phase half-life (t1/2) of VH3810109 [Up to Week 24]
Blood samples will be collected at the indicated time points for PK analysis of VH3810109
- Number of participants with change in dimension score "acceptance of ISRs" using Perception of Injection (PIN) Questionnaire [Day 2 and Day 7]
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.
- Number of participants with Individual item score assessing pain using PIN Questionnaire [Day 2 and Day 7]
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.
- Percentage of participants reporting being bothered or affected by the pain and local reactions based on the PIN Questionnaire [Day 2 and Day 7]
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.
- Percentage of participants with post-injection pain assessment using Numeric Rating Scale (NRS) [Day 1, 2 and 7]
Post-injection assessment of score is measured based on NRS which is a 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain).
- Percentage of participants reporting ISRs overall and by grade [Up to Day 14]
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.
- Duration of ISRs overall and by grade [Up to Day 14]
ISRs will be recorded via ISR diaries and managed through investigator assessment.
- Change from baseline in Platelets, WBC count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils (cells per microliter) [Baseline (Day -1) to Week 24]
- Change from baseline in Hematocrit (percentage) [Baseline (Day -1) to Week 24]
- Change from baseline in Hgb, albumin and total protein (grams per deciliter) [Baseline (Day -1) to Week 24]
- Change from baseline in Red Blood Cell Count (RBC) (million cells per microliter) [Baseline (Day -1) to Week 24]
- Change from baseline in Mean Corpuscle Volume (MCV) (cubic microns) [Baseline (Day -1) to Week 24]
- Change from baseline in Mean Corpuscle Hemoglobin (MCH) (picograms per cell) [Baseline (Day -1) to Week 24]
- Change from baseline in differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (percentage) [Baseline (Day -1) to Week 24]
- Change from baseline in Glucose (fasting), BUN, Creatinine, Direct Bilirubin and Total Bilirubin (milligrams per deciliter) [Baseline (Day -1) to Week 24]
- Change from baseline in Sodium, Potassium, Calcium, Chloride and Carbon Dioxide (milliequivalents per liter) [Baseline (Day -1) to Week 24]
- Change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and alkaline phosphatase (ALP) (International Units per liter) [Baseline (Day -1) to Week 24]
- Change from baseline in urine Specific Gravity (ratio) [Baseline (Day -1) to Week 24]
- Number of participants with presence of Glucose, Protein, Blood, Ketones, Bilirubin, Urobilinogen, Nitrite, Leukocyte Esterase in urine [Baseline (Day -1) to Week 24]
Urine samples will be collected to analyse presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase in urine.
- Urine Potential of Hydrogen (pH) Analysis by Dipstick Method [Baseline (Day -1) to Week 24]
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).
- 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]
- Change from baseline in Temperature [Baseline (Day -1) to Week 24]
- Change from baseline in Pulse Rate [Baseline (Day -1) to Week 24]
- Change from baseline in Respiratory Rate [Baseline (Day -1) to Week 24]
- Change from baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline (Day -1) to Week 24]
Eligibility Criteria
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.
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Participants having body weight of ≥50 kilogram (kg) and <100 kg
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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.
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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:
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Hypertension that is not well controlled.
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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.
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Positive human immunodeficiency virus (HIV) antibody test.
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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
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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.
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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.
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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.
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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).
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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.
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Prior receipt of licensed or investigational Monoclonal antibody (Mab).
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Receipt of any investigational study agent within 28 days prior to first dose of study treatment
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Prior exposure to VH3810109 or rHuPH20 in this or another clinical study.
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Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.
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Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
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ALT ≥1.5 times the upper limit of normal (ULN).
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Total bilirubin ≥1.5 times the ULN (isolated total bilirubin >1.5×ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%).
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Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
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Corrected QT interval Fridericia's formula (QTcF)>450 millisecond (msec) for males and QTcF >470 msec for females.
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The participant has a tattoo or other dermatological condition overlying potential injection sites that may interfere with interpretation of ISRs or administration of VH3810109.
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Grade 4 laboratory abnormalities.
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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.
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Known hypersensitivity to hyaluronidase or any of the excipients in ENHANZE™ Drug Product (EDP)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- ViiV Healthcare
Investigators
- Study Director: GSK Clinical Trials, ViiV Healthcare
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 217901