Study of ALXN1850 in Participants With Hypophosphatasia (HPP)

Study Overview
=================
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.

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

Conditions
-----------------
Hypophosphatasia

Intervention / Treatment
-----------------
* Biological: ALXN1850


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Interventional Model Description: Study participants will be enrolled into 3 cohorts in a sequential fashion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN1850<br>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<br>* ALXN1850 will be administered as an IV infusion and via the SC route.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Of Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events |  | Up to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under The Plasma Concentration Versus Time Curve (AUC) Of Single IV And Multiple SC Doses Of ALXN1850 |  | Predose through up to 168 hours following each dose administration | 
| Maximum Observed Plasma Concentration (Cmax) Of Single IV And Multiple SC Doses Of ALXN1850 |  | Predose through up to 168 hours following each dose administration | 
| Area Under The Plasma Concentration Versus Time Curve Within The Dosing Interval (AUCtau) Values Of The First SC Versus IV Administration |  | Predose through up to 168 hours postdose | 
| Change From Baseline In Plasma Concentrations Of Inorganic Pyrophosphate (PPi) |  | Up to Day 85 | 
| Change From Baseline In Plasma Concentrations Of Pyridoxal-5'-Phosphate (PLP) |  | Up to Day 85 | 
| Change From Baseline In Plasma Concentrations Of PLP/Pyridoxal (PL) Ratio |  | Up to Day 85 | 
| Assess incidence of Antidrug Antibody (ADA) and Neutralizing Antibody (NAbs) |  | Up to Day 85 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HPP, enzyme replacement therapy, low alkaline phosphatase, tissue-nonspecific alkaline phosphatase, TNSALP