Study of ALXN1850 in Participants With Hypophosphatasia (HPP)

NCT04980248 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ALXN1850-HPP-101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

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.

Conditions

Hypophosphatasia

Keywords

HPP; enzyme replacement therapy; low alkaline phosphatase; tissue-nonspecific alkaline phosphatase; TNSALP

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

Study Arms (1)

ALXN1850

EXPERIMENTAL

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

Interventions

ALXN1850 BIOLOGICAL

ALXN1850 will be administered as an IV infusion and via the SC route.

ALXN1850

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (4)

Research Site

Las Vegas, Nevada, 89113, United States

Location

Research Site

Columbus, Ohio, 43203, United States

Location

Research Site

Nashville, Tennessee, 37232, United States

Location

Research Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Dahir KM, Shannon A, Dunn D, Voegtli W, Dong Q, Hasan J, Pradhan R, Pelto R, Pan WJ. Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia. J Bone Miner Res. 2024 Sep 26;39(10):1412-1423. doi: 10.1093/jbmr/zjae128.

  PMID: 39135540 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hypophosphatasia

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study participants will be enrolled into 3 cohorts in a sequential fashion.

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: July 28, 2021
• Study Start: September 28, 2021
• Primary Completion: August 24, 2022
• Study Completion: August 24, 2022
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-11

Locations

US (4)