A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1910 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single ascending doses (SADs) of ALXN1910 subcutaneous (SC) and SAD of ALXN1910 intravenous (IV).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Healthy participants
- •Participants of Japanese descent are defined as: First generation (born to 2 Japanese parents and 4 Japanese grandparents).
- •Participants of Japanese descent must be between 20 and 55 years of age.
排除标准
- •Current or recurrent disease
- •Current or relevant history of physical or psychiatric illness.
- •Any other significant disease or disorder that, in the opinion of the Investigator, may put the participant at risk.
- •History of significant allergic reaction (eg, anaphylaxis or angioedema) to any product (eg, food, pharmaceutical).
- •Female participants who are pregnant or breastfeeding.
- •Major surgery or hospitalization within 90 days prior to dosing on Day
- •History of exposure to asfotase alfa.
- •History of allergy or hypersensitivity to excipients of asfotase alfa or ALXN1910 (eg,sodium phosphate, sodium chloride).
研究组 & 干预措施
Cohort 1
Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.
干预措施: ALXN1910 (Drug)
Cohort 1
Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.
干预措施: Placebo (Drug)
Cohort 2
Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
干预措施: ALXN1910 (Drug)
Cohort 2
Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
干预措施: Placebo (Drug)
Cohort 3
Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.
干预措施: ALXN1910 (Drug)
Cohort 3
Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.
干预措施: Placebo (Drug)
Cohort 4
Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
干预措施: ALXN1910 (Drug)
Cohort 4
Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
干预措施: Placebo (Drug)
Cohort 5
Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.
干预措施: ALXN1910 (Drug)
Cohort 5
Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.
干预措施: Placebo (Drug)
Cohort 6
Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.
干预措施: ALXN1910 (Drug)
Cohort 6
Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
时间窗: Day 1 (postdose) through Day 75
The safety and tolerability of ALXN1910 was assessed.
次要结局
- AUC From Time Zero to 168h (AUC0-168)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Maximum Observed Serum Concentration (Cmax)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Time to Maximum Observed Serum Concentration (Tmax)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Apparent Terminal Elimination Half Life (t1/2)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Terminal-phase Elimination Rate Constant (λz)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- AUC From Time Zero to the Last Quantifiable Concentratio (AUCt)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- AUC From Time Zero Extrapolated to Infinity (AUC∞)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F)(Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75)
- Plasma Concentration of Inorganic Pyrophosphate (PPi)(Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75)
- Plasma Concentration of Pyridoxal (PL)(Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75)
- Plasma Concentration of Pyridoxal 5-Phosphate (PLP)(Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75)
- Plasma Concentration of Pyridoxic Acid (PA)(Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75)
- Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs)(Day 1 (postdose) through Day 75)
- Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910(Up to Day 75)
- Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants(Up to Day 75)
- AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants(Up to Day 75)
- AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants(Up to Day 75)
- Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants(Day 2, 15, 22, 43, and 75)
- Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants(Day 2, 15, 22, 43, and 75)
- Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants(Day 2, 15, 22, 43, and 75)
- Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants(Day 2, 15, 22, 43, and 75)