A Randomized, Double-blind, Single-dose, Parallel-group Design, 2 Arm Study Comparing the Pharmacokinetic, Pharmacodynamic, Safety, Tolerability, and Immunogenicity Profiles of AVT03 and Prolia® in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 209
- 试验地点
- 4
- 主要终点
- Area under the serum concentration-time curve (AUC0-last) from day 0 to day 252
研究概览
简要总结
This study has been designed as a randomized, double-blind, single-dose, parallel-group study in healthy adult male subjects 28 years to 55 years old. The study will assess the PK, PD, safety, tolerability and immunogenicity of AVT03 compared to Prolia when administered as a single SC dose.
详细描述
The study will consist of a 4 week screening period, a 252 day (36 weeks) treatment and assessment period, and an End of Study (EOS) visit on week 36 on Day 252. Subjects will undertake a screening visit between Day -28 and Day -1 to determine their eligibility for the study. On Day 1, eligible subjects will be randomized and will receive a single dose of AVT03 or Prolia as subcutaneous injection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double Blind
入排标准
- 年龄范围
- 28 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male subjects who are 28 to 55 years old, inclusive
- •Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index (BMI) of 17.0 to 32.0 kg/m2 (inclusive)at Screening and Day -1
- •Medical history without evidence of a clinically significant disorder, condition, or disease that, in the opinion of the Investigator, would pose a risk to subject safety
排除标准
- •Any evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism (such as, but not limited to osteoporosis, osteogenesis imperfecta, hyperparathyroidism, hyperthyroidism, hypothyroidism, osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease, Paget's disease of the bone, recent bone fracture [within 6 months], and malabsorption syndrome)
- •Have osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery) within 6 months prior to Day 1 or intend to undergo such procedures during the study period, poor oral hygiene, periodontal, and/or pre existing dental disease
- •Have bone fractures within 6 months prior to Day -
- •Have a history of immunodeficiency
- •Those with skin allergies, or are susceptible to autoinflammatory skin disorders, or prone to the development of allergic skin inflammation
- •Abnormal serum calcium: current hypocalcemia or hypercalcemia at Screening. Serum calcium levels must be within reference ranges.
- •Known vitamin D deficiency
研究组 & 干预措施
Prolia Arm
Prolia(denosumab) is the proposed comparator for AVT03 (denosumab). Subjects in this arm will receive a single 60mg dose of Prolia (denosumab) as a subcutaneous injection.
干预措施: Prolia (Biological)
AVT03 Arm
AVT03 (denosumab) is the proposed biosimilar for Prolia (denosumab). Subjects in this arm will receive a single 60mg dose of AVT03 (denosumab) as a subcutaneous injection.
干预措施: AVT03 (Biological)
结局指标
主要结局
Area under the serum concentration-time curve (AUC0-last) from day 0 to day 252
时间窗: Day 1(week 1) to Day 252 (week 36)
Venous blood samples will be collected for measurement of Area under serum concentration-time curve (AUC 0-t) AVT03 and Prolia
Area under the serum concentration-time curve (AUC0-inf) from day 0 to day 252
时间窗: Time Frame: Day 1(week 1) to Day 252 (week 36)]
Venous blood samples will be collected for measurement of CTX-1 serum biomarker for AVT03 and Prolia.
Maximum serum concentration Cmax from day 0 to day 252
时间窗: Day 1(week 1) to Day 252 (week 36)
Venous blood samples will be collected for measurement of maximum serum concentration (Cmax) of AVT03 and Prolia.
次要结局
- Immunogenicity presence and titers of ADAs and presence of nAbs against AVT03 and Prolia(Time Frame: Day 1(week 1) to Day 252 (week 36))
- PK area under the concentration-time curve (AUC0-24) from Day 0 to Day 252(Day 1(week 1) to Day 162 (week 24)])
- Safety incidence, nature and severity of adverse events(Screening to Day 252 (week 36))
- PD_AUCE0 for CTX-1 (% inhibition)(Day 1(week 1) to Day 252 (week 36))