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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: ALXN1910
Drug: Placebo

Registration Number: NCT05307978

Lead Sponsor: Alexion Pharmaceuticals, Inc.

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 6	ALXN1910	Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.
Cohort 2	Placebo	Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Cohort 1	Placebo	Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.
Cohort 3	ALXN1910	Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.
Cohort 3	Placebo	Participant will receive a single dose of 15 mg of ALXN1910 IV or Placebo IV.
Cohort 4	ALXN1910	Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Cohort 4	Placebo	Japanese participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.
Cohort 5	Placebo	Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.
Cohort 6	Placebo	Participants will receive a single dose of 135 mg of ALXN1910 SC or Placebo SC.
Cohort 5	ALXN1910	Participants will receive a single dose of 45 mg of ALXN1910 SC or Placebo SC.
Cohort 1	ALXN1910	Participants will receive a single dose of 5 mg of ALXN1910 IV or Placebo IV.
Cohort 2	ALXN1910	Participants will receive a single dose of 15 mg of ALXN1910 SC or Placebo SC.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	The Cmax was assessed as PK parameter of single ascending doses of ALXN1910.
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	The Tmax was assed as PK parameter of single ascending doses of ALXN1910.
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	The t1/2 was assed as PK parameter of single ascending doses of ALXN1910.
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	The λz was assed as PK parameter of single ascending doses of ALXN1910.
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	The AUCt was assed as PK parameter of single ascending doses of ALXN1910.
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	The AUC∞ was assed as PK parameter of single ascending doses of ALXN1910.
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	The AUC0-168 was assed as PK parameter of single ascending doses of ALXN1910.
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	The %AUCex was assed as PK parameter of single ascending doses of ALXN1910.
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	The CL or CL/F was assed as PK parameter of single ascending doses of ALXN1910.
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	The Vd or Vd/F was assed as PK parameter of single ascending doses of ALXN1910.
Plasma Concentration of Inorganic Pyrophosphate (PPi)	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75	The plasma concentrations of PPi was assesed.
Plasma Concentration of Pyridoxal (PL)	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75	The plasma concentrations of PL was assessed.
Plasma Concentration of Pyridoxal 5-Phosphate (PLP)	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75	The plasma concentrations of PLP was assessed.
Plasma Concentration of Pyridoxic Acid (PA)	Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75	The plasma concentrations of PA was assessed.
Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs)	Day 1 (postdose) through Day 75	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.
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	The absolute bioavailability GMR AUC∞ of ALXN1910 SC was assessed.
Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants	Up to Day 75	Quantitative assessment of PK parameter (Cmax) was assessed between Japanese and non-Japanese participants.
AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants	Up to Day 75	Quantitative assessment of PK parameter (AUCt) was assessed between Japanese and non-Japanese participants.
AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants	Up to Day 75	Quantitative assessment of PK parameter (AUC∞) was assessed between Japanese and non-Japanese participants.
Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants	Day 2, 15, 22, 43, and 75	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.
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 PD parameter Pyridoxal-5-phosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment
Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants	Day 2, 15, 22, 43, and 75	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.
Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants	Day 2, 15, 22, 43, and 75	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.