A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1910 in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- ALXN1910
- Conditions
- Healthy
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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).
Arms & Interventions
Cohort 1
Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.
Intervention: ALXN1910
Cohort 1
Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.
Intervention: Placebo
Cohort 2
Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Intervention: ALXN1910
Cohort 2
Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Intervention: Placebo
Cohort 3
Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.
Intervention: ALXN1910
Cohort 3
Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.
Intervention: Placebo
Cohort 4
Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Intervention: ALXN1910
Cohort 4
Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Intervention: Placebo
Cohort 5
Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.
Intervention: ALXN1910
Cohort 5
Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.
Intervention: Placebo
Cohort 6
Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.
Intervention: ALXN1910
Cohort 6
Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Time Frame: Day 1 (postdose) through Day 75
The safety and tolerability of ALXN1910 was assessed.
Secondary Outcomes
- 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)