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

Study Overview
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Brief Summary
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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).

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: ALXN1910
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |  | Day 1 (postdose) through Day 75 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Area Under the Serum Concentration-Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (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 | 
| Number of Participants With Treatment-Emergent Antidrug Antibodies (ADAs) |  | Day 1 (postdose) through Day 75 | 
| Plasma Concentration of Inorganic Pyrophosphate (PPi), Pyridoxal-5'-phosphate (PLP), Pyridoxal (PL), and Pyridoxic Acid |  | Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75 | 
| Geometric Mean Ratio (GMR) of Area Under the Curve (AUC) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALXN1910, Safety, Pharmacokinetics, Pharmacodynamics, Japanese Descent