Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Hypophosphatasia (EmPATHY)

An Observational, Longitudinal Study to Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Pediatric-Onset Hypophosphatasia

Hypophosphatasia is a rare inherited metabolic disorder due to inactivating mutations of the ALPL-Gene. Particularly among adult patients, clinical manifestation exhibits a broad range of signs and symptoms, most commonly associated with musculoskeletal disabilities and compromised quality of life. Enzyme replacement therapy with Asfotase alfa (AA) is available and approved for patients with pediatric onset of the disease.

This single-center observational cohort study aims at collecting clinical routine data regarding the course treatment, quality of life and physical performance in patients treated with Asfotase alfa in line with the label for pediatric-onset hypophosphatasia.

Study Overview

• Status: Completed
• Conditions: Hypophosphatasia

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

Study Locations

• Germany
  • Würzburg, Germany, 97074
    • Clinical Trial Unit, Orthopedic Department, Wuerzburg University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study population consists of male and female HPP patients with pediatric-onset HPP currently being managed for the disease at the Orthopedic Institute of the Julius-Maximilians-University Würzburg, Germany and receiving commercial AA treatment as per the standard of care.

Description

Inclusion Criteria:

• Age ≥ 18 years at the time of enrollment
• Clinical diagnosis of pediatric-onset HPP based on low ALP (age- and sex-adjusted) and/or genetic confirmation of ALPL mutation(s), and clinical symptoms consistent with HPP
• Participant currently receiving commercial asfotase alfa treatment for HPP at the Orthopedic Institute of the Julius-Maximilians-University Würzburg, as per standard of care
• Willingness to participate in the study
• Signed informed consent

Exclusion Criteria:

• Unwillingness / anticipated inability to attend further visits
• Off-label treatment with asfotase alfa
• Current participation in an Alexion Sponsored Trial
• Experimental drug/treatment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pediatric-onset Hypophosphatasia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Performance	6 Minute Walk Test [meters]	1 year of treatment compared to pre-treatment baseline
Physical Performance	Short Physical Performance Battery [points]	1 year of treatment compared to pre-treatment baseline
Physical Performance	Timed Up and Go Test [seconds]	1 year of treatment compared to pre-treatment baseline
Physical Performance	Handheld dynamometry [kilogram]	1 year of treatment compared to pre-treatment baseline
Physical Performance	Jumping mechanography [W/kg bodyweight]	1 year of treatment compared to pre-treatment baseline
Physical Performance	Use of assistive devices descriptive measure	1 year of treatment compared to pre-treatment baseline
Body composition	Bioelectrical Impedance Analysis [proportional mass of muscle, water and fat in kg]	1 year of treatment compared to pre-treatment baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health related quality of life	Questionnaire	1 year of treatment compared to pre-treatment baseline
Bone Mineral Density	Dual x-ray absorptiometry (DXA)	1 year of treatment compared to pre-treatment baseline
Skeletal pathology	Descriptive assessment of available imaging (x-Ray, CT, MRI, histological sections)	1 year of treatment compared to pre-treatment baseline
Laboratory evaluation	Parathyroid hormone [PTH, pg/ml]	1 year of treatment compared to pre-treatment baseline
Laboratory evaluation	Serum-Calcium [mmol/l]	1 year of treatment compared to pre-treatment baseline
Laboratory evaluation	Serum-Phosphorus [mmol/l]	1 year of treatment compared to pre-treatment baseline
Laboratory evaluation	Serum-Creatinine [µmol/l], incl. calculated eGFR	1 year of treatment compared to pre-treatment baseline
Laboratory evaluation	Fibroblast Growth Factor 23 / FGF-23 [RU/ml]	1 year of treatment compared to pre-treatment baseline
Safety assessment	Injection site reactions (descriptive)	1 year of treatment compared to pre-treatment baseline
Safety assessment	Injection associated reactions (descriptive)	1 year of treatment compared to pre-treatment baseline
Safety assessment	Ectopic calcifications (descriptive)	1 year of treatment compared to pre-treatment baseline
Safety assessment	Adverse events (descriptive)	1 year of treatment compared to pre-treatment baseline

Collaborators and Investigators

• Sponsor: Dr. Lothar Seefried
• Collaborators: Alexion Pharmaceuticals
• Investigators: Principal Investigator: Lothar Seefried, MD, Wuerzburg University, Orthopedic Institute, Clinical Trial Unit

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 5, 2018
• Primary Completion (ACTUAL): May 31, 2021
• Study Completion (ACTUAL): May 31, 2021

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (ACTUAL): February 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Hypophosphatasia
• Other Study ID Numbers: KLH-01-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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