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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Arthritis, Rheumatoid
- Sponsor
- Synermore Biologics Co., Ltd.
- Enrollment
- 94
- Locations
- 1
- Primary Endpoint
- λz (elimination rate constant)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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)
Outcomes
Primary Outcomes
λz (elimination rate constant)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)]
Time Frame: 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)
Time Frame: 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)]
Time Frame: 85 days
Vz/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
Secondary Outcomes
- 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)