A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of ADM03820 in Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- The Number of Participants With Serious Adverse Events Following Administration of ADM03820 to the Final Visit
研究概览
简要总结
This is a phase 1, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, pharmacokinetics, and immunogenicity of ADM03820 administered as IM injections in healthy adults for the prevention of COVID-19.
详细描述
The primary objective of this study is to assess the safety and tolerability of escalating IM doses of ADM03820 in healthy adults. Secondary objectives include assessing the pharmacokinetic characteristics and immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Informed consent understood and signed
- •Healthy male or healthy, non-pregnant, non-lactating female
- •Willingness to comply and be available for all protocol procedures for the duration of the study
- •Between the ages of 18 and 55, inclusive on the day of dosing
- •Body Mass Index (BMI) of ≥18.5 and ≤35 kg/m2
- •Female subjects of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test on Day 1 prior to dosing.
- •Note: A woman is considered of childbearing potential unless post-menopausal (> or = 1 year without menses without other known or suspected cause and appropriately elevated FSH) or surgically sterilized via bilateral oophorectomy or hysterectomy
- •Females of childbearing potential and males agree to use acceptable contraception for the duration of the study
- •Note: These include progestin implants, intrauterine devices (IUDs), surgical (hysterectomy or tubal ligation; vasectomy) or abstinence. Use of methods such as progestin injectables, combined oral hormonal contraceptives, condoms, and diaphragms will not be acceptable when used alone, but they could be considered, if used in combination with another method (for example, a female using combined oral contraceptives if her male partner is sterile, or if she and her non-sterile male partner use a double-barrier method), after consultation with the Ology Bioservices MM. All males will be required to use a barrier method (condoms) for the duration of the study
- •Screening laboratory tests are within normal ranges or outside the normal ranges and considered not clinically significant by the Principal Investigator
- •If urinalysis by dipstick is abnormal, a complete urinalysis with microscopic evaluation will be performed and the results will supersede the results of the dipstick for blood, glucose, and protein.
- •Menstruating females failing inclusion criteria due to a positive blood on urine test may be retested following cessation of menses.
- •Other laboratory values that are outside the range of eligibility but are thought to be due to an acute condition or collection or laboratory error may be repeated once.
- •The urine drug screen is negative
- •Breathalyzer test or blood/saliva alcohol test is negative and subject agrees to abstain from alcohol consumption for a period of 2 days prior to dosing and 2 days prior to any study visit.
- •Agree to minimize risk of SARS-CoV-2 infection.
排除标准
- •History of chronic medical condition that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject.
- •Subjects with cardiovascular disease
- •Subjects with diabetes
- •Subjects with pulmonary diseases such as COPD or asthma
- •History of severe allergic reactions of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobins.
- •A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds)
- •Clinically significant abnormal electrocardiogram at screening.
- •Note: Clinically significant abnormal ECG results include but not limited to:
- •complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator
- •Incomplete right bundle branch block is not exclusionary if there are no abnormal ECG findings and there is no clinical history or evidence on physical examination to indicate cardiac disease.
- •Positive serology results for HIV, HBsAg, or HCV antibodies
- •Febrile illness with temperature ≥38°C within 7 days of dosing
- •Female subject who is pregnant or breastfeeding
- •Donated blood within 56 days of enrollment
- •Known allergic reactions to any of the study product components present in the formulation or in the processing, as listed in the Investigator Brochure
- •Treatment with another investigational drug within 28 days of dosing
- •Treatment with a monoclonal antibody within 3 months of enrollment
- •Positive serology results for SARS-CoV-2 antibodies (Not applicable for Cohort 5).
- •Positive results from a reverse transcriptase polymerase chain reaction (RT PCR) test for SARS CoV 2
- •Receipt of antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) or blood transfusion within 6 months or within 5 half-lives of the specific product given
- •Active drug or alcohol use disorder or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
- •Use of H1 antihistamines or beta-blockers within 5 days of dosing
- •Use of any prohibited medication within 28 days prior to screening or planned use during the study period
- •Note: Prohibited medications include immunosuppressives (except Nonsteroidal Anti-Inflammatory Drugs [NSAIDS]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents
- •Any specific condition that in the judgment of the investigator precludes participation because it could affect subject safety
- •Plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period
- •Note: Includes trials that have a study intervention such as a drug, biologic, or device
- •Is a study site employee or staff
- •Note: Site employees or staff include the PIs and sub-investigators or staff who are supervised by the PI or Sub-Investigators
- •Received an approved COVID-19 vaccine (subjects can receive an approved COVID-19 vaccine after completing their Day 90 visit). For Cohort 5, subjects who received a COVID-19 vaccine within 14 days prior to enrollment are excluded.
研究组 & 干预措施
Cohort 1: 150 mg IM injection of active drug or placebo
Subjects in cohort 1 will receive a 150 mg dose IM injection of either active drug or placebo.
Cohort 1 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: ADM03820 (Drug)
Cohort 1: 150 mg IM injection of active drug or placebo
Subjects in cohort 1 will receive a 150 mg dose IM injection of either active drug or placebo.
Cohort 1 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: Placebo (Other)
Cohort 2: 300 mg IM injection of active drug or placebo
Subjects in cohort 2 will receive 300 mg IM injection of either active drug or placebo.
Cohort 2 will dose 8 subjects to active drug and 2 subject to placebo.
干预措施: ADM03820 (Drug)
Cohort 2: 300 mg IM injection of active drug or placebo
Subjects in cohort 2 will receive 300 mg IM injection of either active drug or placebo.
Cohort 2 will dose 8 subjects to active drug and 2 subject to placebo.
干预措施: Placebo (Other)
Cohort 3: 300 mg IM injection of active drug or placebo
Subjects in cohort 3 will receive 300 mg IM injection of either active drug or placebo.
Cohort 3 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: ADM03820 (Drug)
Cohort 3: 300 mg IM injection of active drug or placebo
Subjects in cohort 3 will receive 300 mg IM injection of either active drug or placebo.
Cohort 3 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: Placebo (Other)
Cohort 4: 300 mg IM injection of active drug or placebo
Subjects in cohort 4 will receive 300 mg IM injection of either active drug or placebo.
Cohort 4 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: ADM03820 (Drug)
Cohort 4: 300 mg IM injection of active drug or placebo
Subjects in cohort 4 will receive 300 mg IM injection of either active drug or placebo.
Cohort 4 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: Placebo (Other)
Cohort 5: 600 mg IM injection of active drug or placebo
Subjects in cohort 5 will receive 600 mg IM injection of either active drug or placebo.
Cohort 5 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: ADM03820 (Drug)
Cohort 5: 600 mg IM injection of active drug or placebo
Subjects in cohort 5 will receive 600 mg IM injection of either active drug or placebo.
Cohort 5 will dose 8 subjects to active drug and 2 subject to placebo
干预措施: Placebo (Other)
结局指标
主要结局
The Number of Participants With Serious Adverse Events Following Administration of ADM03820 to the Final Visit
时间窗: 540 days for Cohorts 1-4, 365 days for Cohort 5, and up to 540 days for placebo
Determine number of SAEs after dosing through the final visit
The Number of Participants With AEs Following Administration of ADM03820 to the Final Visit
时间窗: 540 days for Cohorts 1-4, 365 days for Cohort 5, and up to 540 days for placebo
Determine the number of AEs after dosing
The Number of Participants With Changes From Baseline in Physical Examination, Vital Signs, and Clinical Safety Laboratory Values Following Administration of ADM03820 to the Final Visit
时间窗: 540 days
The number of participants that were includes in this data are those who had clinically significant physical examinations, vital signs, and clinical safety laboratory values following administration of ADM03820 to the final visit.
次要结局
- The Assessment of Peak Plasma Concentration (Cmax) for Total Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 1-2).(pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365)
- The Assessment of Tmax for Total Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 1-2).(pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365)
- The Assessment of the Area Under the Plasma Concentration (AUC(0-t)) for the Total Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 1-2).(pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365)
- The Assessment of Peak Plasma Concentration (Cmax) for Each of the Monoclonal Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 3-5).(pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365)
- The Assessment of Tmax for Each of the Monoclonal Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 3-5).(pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365)
- The Assessment of Area Under the Plasma Concentration (AUC(0-t)) for Each of the Monoclonal Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 3-5).(pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365)
- Presence of Anti-drug Antibody (ADA) Levels(pre-dose, and Day 15, 30, 45, 60, 90, 120, 150, and 180)
- The Number of Participants With SARS-CoV-2 RT-PCR Positive Symptomatic Illness Occurring After Dosing(365 days)
- The Number of Participants With SARS-CoV-2 RT-PCR Positive Severe or Critical Symptomatic Illness Occurring After Dosing(365 days)
- The Number of Participants With COVID-19 Related Emergency Department Visits Occurring After Dosing(365 days)
- The Presence of Neutralizing Antibody Concentrations of ADM03820 as Measured by Microneutralization (MN) Methods(180 days)