Study of ALXN1850 in Participants With Hypophosphatasia (HPP)

Phase 1

Completed

• Conditions: Hypophosphatasia
• Interventions: Biological: ALXN1850

• Registration Number: NCT04980248
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-23
• Study First Submitted QC: 2021-07-23
• Study First Posted: 2021-07-28
• Study Start: 2021-09-28
• Primary Completion: 2022-08-24
• Study Completion: 2022-08-24
• Results First Submitted: 2024-07-26
• Status Verified: 2024-11
• Results First Submitted QC: 2024-11-08
• Last Update Submitted: 2024-11-08
• Results First Posted: 2024-12-27
• Last Update Posted: 2024-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ALXN1850	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	Day 1 up to Day 85	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.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Research Site; 🇺🇸 Austin, Texas, United States