Safety and Tolerability, Pharmacokinetic, and Pharmacodynamic Study of ALXN1910 in Healthy Participants

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1910 in Healthy Adult Participants

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN1910; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Day1.
• History of exposure to asfotase alfa.
• History of allergy or hypersensitivity to excipients of asfotase alfa or ALXN1910 (eg,sodium phosphate, sodium chloride).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.	Drug: ALXN1910; Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.; Drug: Placebo; Participants will receive Placebo IV or Placebo SC according to their assigned cohort.
Experimental: Cohort 2; Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.	Drug: ALXN1910; Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.; Drug: Placebo; Participants will receive Placebo IV or Placebo SC according to their assigned cohort.
Experimental: Cohort 3; Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.	Drug: ALXN1910; Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.; Drug: Placebo; Participants will receive Placebo IV or Placebo SC according to their assigned cohort.
Experimental: Cohort 4; Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.	Drug: ALXN1910; Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.; Drug: Placebo; Participants will receive Placebo IV or Placebo SC according to their assigned cohort.
Experimental: Cohort 5; Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.	Drug: ALXN1910; Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.; Drug: Placebo; Participants will receive Placebo IV or Placebo SC according to their assigned cohort.
Experimental: Cohort 6; Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.	Drug: ALXN1910; Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.; Drug: Placebo; Participants will receive Placebo IV or Placebo SC according to their assigned cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	The safety and tolerability of ALXN1910 was assessed.	Day 1 (postdose) through Day 75

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax)	The Cmax was assessed as PK parameter of single ascending doses of ALXN1910.	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)	The Tmax was assed as PK parameter of single ascending doses of ALXN1910.	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)	The t1/2 was assed as PK parameter of single ascending doses of ALXN1910.	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)	The λz was assed as PK parameter of single ascending doses of ALXN1910.	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)	The AUCt was assed as PK parameter of single ascending doses of ALXN1910.	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∞)	The AUC∞ was assed as PK parameter of single ascending doses of ALXN1910.	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 168h (AUC0-168)	The AUC0-168 was assed as PK parameter of single ascending doses of ALXN1910.	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)	The %AUCex was assed as PK parameter of single ascending doses of ALXN1910.	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)	The CL or CL/F was assed as PK parameter of single ascending doses of ALXN1910.	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)	The Vd or Vd/F was assed as PK parameter of single ascending doses of ALXN1910.	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)	The plasma concentrations of PPi was assesed.	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Plasma Concentration of Pyridoxal (PL)	The plasma concentrations of PL was assessed.	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Plasma Concentration of Pyridoxal 5-Phosphate (PLP)	The plasma concentrations of PLP was assessed.	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Plasma Concentration of Pyridoxic Acid (PA)	The plasma concentrations of PA was assessed.	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs)	The ADAs of ALXN1910 was assessed as immunogenicity parameter. Treatment-emergent ADA Responses is defined as a positive result in the ADA assay post first dose, when baseline results are negative or missing.	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	The absolute bioavailability GMR AUC∞ of ALXN1910 SC was assessed.	Up to Day 75
Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants	Quantitative assessment of PK parameter (Cmax) was assessed between 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	Quantitative assessment of PK parameter (AUCt) was assessed between Japanese and non-Japanese participants.	Up to Day 75
AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants	Quantitative assessment of PK parameter (AUC∞) was assessed between Japanese and non-Japanese participants.	Up to Day 75
Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants	Change from baseline in PD parameter Inorganic Pyrophosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment.	Day 2, 15, 22, 43, and 75
Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants	Change from baseline in PD parameter Pyridoxal-5-phosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment	Day 2, 15, 22, 43, and 75
Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants	Change from baseline in PD parameter Pyridoxal was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment.	Day 2, 15, 22, 43, and 75
Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants	Change from baseline in PD parameter Pyridoxic Acid was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment.	Day 2, 15, 22, 43, and 75

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2022
• Primary Completion (Actual): February 7, 2023
• Study Completion (Actual): February 7, 2023

Study Registration Dates

• First Submitted: March 24, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Pharmacodynamics; Japanese Descent; ALXN1910
• Other Study ID Numbers: ALXN1910-HV-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No