Relieving Burden of Hypophosphatasia in Adults With Functional Impairment Due to Chronic Disease (REBUILD)

A Phase 4, Randomized, Multicenter, Open-Label, 2-Dosage Regimen, Safety and Tolerability, Efficacy, Pharmacokinetic, and Pharmacodynamic Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia

The study will evaluate safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of 2 different doses (approved dose and lower dose) of asfotase alfa in adult participants with pediatric-onset hypophosphatasia (HPP).

Study Overview

• Status: Withdrawn
• Conditions: Hypophosphatasia
• Intervention / Treatment: Drug: asfotase alfa

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female aged ≥ 18 years at the time of signing the informed consent form
• Clinical diagnosis of pediatric-onset HPP based on signs and symptoms consistent with HPP
• Past medical history that includes at least one nonvertebral fracture (or pseudofracture) incurred without evidence of significant trauma.
• The presence of a current fracture is not necessary, but for participants with current unhealed fracture(s) or pseudofracture(s) of the lower extremity(ies) (that is, femoral, tibial, fibular, metatarsal) documentation must be provided of the presence of these fractures for at least 3 months prior to screening (with or without surgical intervention)

Exclusion Criteria:

• Medical condition, serious concurrent or recurrent illness and/or injury, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance or the assessment of study endpoints, including all protocol required evaluations and follow up activities, or may put the patient at risk
• Primary or secondary hyperparathyroidism or hypoparathyroidism
• History of hypersensitivity to any ingredient contained in asfotase alfa
• Oral bisphosphonate use within 6 to 12 months (depending on the half-life of the drug as assessed by the investigator) and intravenous (IV) bisphosphonate use within 12 months prior to screening
• Denosumab use within 18 months prior to screening
• Asfotase alfa use within 6 months prior to screening
• Teriparatide/parathyroid hormone analog use within 2 months prior to screening
• Treatment with strontium or sclerostin inhibitors within 6 months prior to the first dose of study drug
• Vitamin B6 use for at least 2 weeks prior to screening
• Serum 25-hydroxy (25-OH) vitamin D below 20 nanogram (ng)/milliliter (mL), with repletion and recheck allowed at screening (results from local laboratory may be used if within 4 weeks of screening)
• Female patients who are pregnant, planning to become pregnant, or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 Asfotase Alfa; Participants will be administered asfotase alfa per approved dose for 36 weeks.	Drug: asfotase alfa; Asfotase alfa is administered subcutaneously.
Experimental: Group 2 Asfotase Alfa; Participants will be administered asfotase alfa per approved dose for 12 weeks and then asfotase alfa at a lower dose for 24 weeks.	Drug: asfotase alfa; Asfotase alfa is administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline To Week 36 In Plasma Concentrations Of Inorganic Pyrophosphate (PPi) In Group 1	Baseline, Week 36

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline To Week 36 In Plasma Concentrations Of PPi In Group 2	Baseline, Week 36
Change From Baseline To Week 36 In The 36-item Short-Form Survey (SF-36) Physical Component Summary (PCS) Score In Groups 1 And 2	Baseline, Week 36
Change From Baseline To Week 36 In The Repeated Chair Stand Test (A Component Of The Short Physical Performance Battery [SPPB]) In Groups 1 And 2	Baseline, Week 36

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 1, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Hypophosphatasia; HPP; Pediatric-Onset; Asfotase Alfa
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Hypophosphatasia
• Other Study ID Numbers: AA-HPP-406

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