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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Grade 2 or Higher (>=) Adverse Events (AEs) Following SC Administration of VH3810109 (Part 1 and Part 3)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This will be an open-label study. Hence, there will be no masking.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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-
- •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 VH
- •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)
研究组 & 干预措施
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.
干预措施: VH3810109 (Biological)
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.
干预措施: rHuPH20 (Biological)
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.
干预措施: VH3810109 (Biological)
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.
干预措施: VH3810109 (Biological)
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.
干预措施: rHuPH20 (Biological)
结局指标
主要结局
Number of Participants With Grade 2 or Higher (>=) Adverse Events (AEs) Following SC Administration of VH3810109 (Part 1 and Part 3)
时间窗: 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 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.
Number of Participants With Serious Adverse Events (SAEs) Following SC Administration of VH3810109 (Part 1 and Part 3)
时间窗: Up to Week 24
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.
Number of Participants With Injection Site Reactions (ISRs) Following VH3810109 SC Administration (Part 1 and 3)
时间窗: Up to 7 days post-dose
ISRs were recorded via ISR diaries and managed through investigator assessment. The participants who experienced any injection site reaction were reported.
Number of Participants With Grade 2 to 4 Elevated Alanin Aminotransferase/Aspartate Aminotransferase (ALT/AST) Values Following VH3810109 SC Administration (Part 1 and 3)
时间窗: 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.
Number of Participants With >= Grade 2 AEs Following IV Administration of VH3810109 (Part 2)
时间窗: 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 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.
Number of Participants With SAEs Following IV Administration of VH3810109 (Part 2)
时间窗: Up to Week 24
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.
Number of Participants With Grade 2 to 4 Elevated ALT/AST Values Following VH3810109 IV Administration (Part 2)
时间窗: 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.
次要结局
- Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) of VH3810109(Up to Week 24)
- AUC From Time Zero to Time t (AUC[0-t]) of VH3810109(Up to Week 24)
- Maximum Observed Concentration (Cmax) of VH3810109(Up to Week 24)
- Time of Maximum Observed Concentration (Tmax) of VH3810109(Up to Week 24)
- Apparent Terminal Phase Half-life (t1/2) of VH3810109(Up to Week 24)
- Score Recorded for "Acceptance of ISRs", Using Perception of Injection (PIN) Questionnaire (Part 1 and 3)(At Day 2 and Day 7)
- Number of Participants Reporting Pain, Using Perception of Injection (PIN) Questionnaire (Part 1 and 3)(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)(At Day 2 and Day 7)
- Scores Reported for Post-injection Pain Assessment Using Numeric Rating Scale (NRS) Following VH3810109 IV Administration (Part 2)(At Day 1, 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)(At Day 1, Day 2 and Day 7)
- Number of ISRs Events Overall and by Grade (Part 1 and 3)(Up to day 14)
- The Overall Duration of ISRs, Expressed in Days(From Day 1 up to Day 14)
- Change From Baseline in Platelets, White Blood Cells (WBC), Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Hematocrit(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Hemoglobin, Albumin and Total Protein(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Red Blood Cell Count (RBC)(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Mean Corpuscle Volume (MCV)(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Mean Corpuscle Hemoglobin (MCH)(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Direct Bilirubin and Total Bilirubin(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Sodium, Potassium, Calcium, Chloride and Carbon Dioxide(From Baseline (Day -1) up to Week 24)
- Change From Baseline in ALT, AST and Alkaline Phosphatase (ALP)(From Baseline (Day -1) up to Week 24)
- Number of Participants With Worst Case Urinalysis at Post-baseline Compared With Baseline(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)(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Temperature(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Pulse Rate(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Respiratory Rate(From Baseline (Day -1) up to Week 24)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(From Baseline (Day -1) up to Week 24)