A Phase 1 Randomized Blinded Single Dose Comparison of the Safety and Pharmacokinetics of SYN060 Compared to Adalimumab (Humira®) From North American and European Sources in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 94
- 试验地点
- 2
- 主要终点
- λz (elimination rate constant)
研究概览
简要总结
This is a single site, parallel randomized, double blinded comparison of the safety, pharmacokinetics, and immunogenicity of a single 0.57 mg/kg dose of SYN060 to a single 0.57 mg/kg dose of adalimumab (Humira®) reference product from North American and European sources. The study is open to healthy individuals on no medications that might confound the results of this safety study.
详细描述
This is a single site, parallel randomized, double blinded comparison of the safety, pharmacokinetics, and immunogenicity of a single 0.57 mg/kg dose of SYN060 to a single 0.57 mg/kg dose of adalimumab (Humira®) reference product from North American and European sources. The study is open to healthy individuals on no medications that might confound the results of this safety study.
A total of 90 subjects will be randomized in a 1:1:1 ratio to from a centrally generated randomization schedule to SYN060 or adalimumab of American or European sources resulting in 30 subjects in each group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female subjects between 18 and 50 years of age, inclusive
- •Body mass index between 18 and 30 kg/m², inclusive
- •Female subjects physically capable of pregnancy (i.e., not sterilized and still menstruating or within 1 year of the last menses if menopausal) must:
- •Agree to avoid pregnancy from the Study Day screening visit through six months after receipt of Study Drug.
- •If in a sexual relationship with a man, use an acceptable method of avoiding pregnancy during this period, still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring or intrauterine device (IUD).
- •Women of childbearing potential must have a negative serum pregnancy test within 24 hours preceding receipt of the dose.
- •Can understand and sign the informed consent document, can communicate with the investigator and provide updated contact information as needed for the duration of the study, has no current plans to move from the study area for the duration of the study, and can understand and comply with the requirements of the protocol.
排除标准
- •Acute illness on Study Day 1
- •Oral temperature ≥37.5°C on Study Day 1
- •Inability to discontinue daily medications other than oral contraceptives or other hormonal therapy.
- •Receipt of an immunoglobulin or blood product within 90 days prior to Study Day 1
- •Any receipt of adalimumab, or other licensed monoclonal antibody
- •Any receipt of another investigational product within 4 weeks or 4 half-lives whichever is longer prior to Study Day 1
- •Abnormal laboratory values per local laboratory parameters from blood collected at screening prior to Study Day 1 randomization as follows:
- •Severe anemia, defined as haemoglobin <100 g/L or hematocrit <0.3 L/L
- •absolute neutrophil count, below lower limit of normal (LLN)
- •white blood cell count above upper limit of normal (ULN) or below LLN (i.e., must be within normal limits)
- •ALT, AST, alkaline phosphatase (ALP) above ULN with exception that a one of the three values may be permitted up to 10% above ULN.
- •Creatinine above upper limit of normal ,
- •INR, or activated partial thromboplastin time (APTT) above ULN
- •Abnormal screening urinalysis result that is, per the investigator, clinically significant, or a screening urine dipstick result of ≥2+ protein
- •Positive screening urine test for illicit drugs (amphetamines, methamphetamines, barbiturates, benzodiazepine, cocaine, opiates, PCP, MDMA, methadone)
- •History of systemic allergic reactions, to more than one medication.
- •History or evidence of malignancy.
- •Receipt of immunosuppressive medications other than inhaled or topical immunosuppressant drugs such as corticosteroids within 45 days prior to Study Day 1
- •Hepatitis B surface antigen positive, HIV positive, hepatitis C antibody positive
- •Uncontrolled Type 2 Diabetes or Type I diabetes
- •History systemic fungal infection.
- •Shared a residence within the last year with an individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis
- •Previous medical history that may compromise the safety of the subject in the study, including but not limited to: severe impairment of pulmonary function or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease or poorly controlled epilepsy
- •History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety of the Study Drug
- •History or evidence of tuberculosis infection
- •Positive Quantiferon test
- •Chest X ray with evidence of malignancy or chronic infection (such as tuberculosis or other)
- •Any current medical, psychiatric, occupational, or substance abuse problem such as alcoholism that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol.
- •Elective surgery that would interfere with participation.
- •Live virus vaccination within 60 days and during the study.
- •Blood donation less than 30 days prior to Study Day 1.
研究组 & 干预措施
Adalimumab North American source
a single 0.57 mg/kg dose of adalimumab from North American source
干预措施: Adalimumab North American source (Biological)
Adalimumab European source
a single 0.57 mg/kg dose of adalimumab from European source
干预措施: Adalimumab European source (Biological)
SYN060
a single 0.57 mg/kg dose of SYN060
干预措施: SYN060 (Biological)
结局指标
主要结局
λz (elimination rate constant)
时间窗: 85 days
λz will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
CL/F (apparent body clearance, calculated as Dose/AUC0-inf)
时间窗: 85 days
CL/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
Cmax (maximum observed concentration)
时间窗: 85 days
Cmax will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
Tmax (time of observed Cmax)
时间窗: 85 days
Tmax will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
AUC0-last (area under the concentration-time curve from time zero to the last non-zero concentration) and AUC0-inf (area under the concentration-time curve from time zero to infinity)
时间窗: 85 days
AUC0-last and AUC0-inf will be estimated using non-compartmental analysis fpr SYN060 to adalimumab (Humira®) from North American and European sources.
Residual area (%AUCextrap) [percent extrapolated area under the curve to infinity calculated as 100*(1- AUC0-last / AUC0-inf)]
时间窗: 85 days
Residual area (%AUCextrap) will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
t½ (elimination half-life)
时间窗: 85 days
t½ will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
Vz/F [apparent volume of distribution, calculated as Dose/ (λz x AUC0-inf)]
时间窗: 85 days
Vz/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
次要结局
- Adverse event incidence of SYN060 compared to adalimumab (Humira®) from North American and European sources(85 days)
- anti-SYN060 antibodies(85 days)
- anti-adalimumab antibodies(85 days)