Study of ALXN1850 in Participants With Hypophosphatasia (HPP)

A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia

This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.

Study Overview

• Status: Completed
• Conditions: Hypophosphatasia
• Intervention / Treatment: Biological: ALXN1850

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Austin, Texas, United States, 78744
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed clinical diagnosis of HPP
• Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion
• Willing and able to follow protocol-specified contraception requirements
• Willing and able to give informed consent

Exclusion Criteria:

• Primary or secondary hyperparathyroidism or hypoparathyroidism
• Fracture within 12 weeks of screening
• Current or relevant history of unstable physical or psychiatric illness
• Significant allergies
• Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1850; Three experimental cohorts will be administered 3 dosages (low, medium, high) of ALXN1850, respectively, via IV infusion and/or SC over multiple administration intervals.	Biological: ALXN1850; ALXN1850 will be administered as an IV infusion and via the SC route.

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)	TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Day 1 up to Day 85

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3	Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850	Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3	Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850	Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1	Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1	Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1	Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP at Week 1	Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PPi at Week 1	Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1	Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status	Baseline up to Day 85

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): August 24, 2022
• Study Completion (Actual): August 24, 2022

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; HPP; low alkaline phosphatase; tissue-nonspecific alkaline phosphatase; TNSALP
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Metal Metabolism, Inborn Errors; Hypophosphatasia
• Other Study ID Numbers: ALXN1850-HPP-101

Drug and device information, study documents

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