Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia

Open-Label Pilot Trial to Evaluate the Effects of Ilofotase Alfa on Biomarkers in Adult Patients With Hypophosphatasia

The goal of this clinical trial is to compare the effectiveness of two doses of ilofotase alfa, an enzyme replacement treatment, in patients with hypophosphatasia (HPP). The main question it aims to answer is if the harmful accumulating levels of extracellular inorganic pyrophosphate (PPi) and pyridoxal 5'-phosphate (PLP) can be reduced with ilofotase alfa.

Researchers will compare the two doses of ilofotase alfa to see if treatment effects differ between the doses.

Study Overview

• Status: Completed
• Conditions: Hypophosphatasia
• Intervention / Treatment: Biological: Ilofotase Alfa, 0.8 mg/kg; Biological: Ilofotase Alfa, 3.2 mg/kg

Detailed Description

Recombinant human alkaline phosphatase (ilofotase alfa) is a full-length human chimeric alkaline phosphatase (ALP) that could benefit patients with hypophosphatasia (HPP), which is characterized by low activity of tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP).

This is a pilot trial for a potential future trial aimed at identifying whether treatment with ilofotase alfa can normalize circulating levels of PPi, PLP and other biochemical markers of TNSALP deficiency along with the safety/tolerability of different doses of ilofotase alfa. The trial is designed as a single-center, open-label, randomized, parallel group clinical trial in adult patients with HPP. Two different dose levels (0.8 mg/kg and 3.2 mg/kg) of ilofotase alfa will be assessed.

Participants will receive a single dose of ilofotase alfa, administered as a 1-hour intravenous infusion on Study Day 1. Participants will stay at the research center for a total of 12 days; from 2 days before study drug administration (run-in) to 10 days after treatment. An additional follow-up assessment is scheduled 14 days after administration of ilofotase alfa.

Blood and urine samples will be taken daily for drug concentration and laboratory measurements assessing safety and effectiveness of treatment. In addition physical examinations will be performed on Day 1 and as needed afterwards.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Würzburg, Germany, 97074
    • Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Genetically confirmed variant in the tissue-nonspecific isozyme alkaline phosphatase (ALPL)-Gene.
• Clinical symptoms of HPP.
• Medical history with 1) at least two independent measures of Alkaline Phosphatase (ALP) below lower level of normal (LLN) and 2) at least one measurement of either PPi or PLP above upper level of normal (ULN).
• Provision of signed and dated informed consent form (ICF) in accordance with local regulations at screening.
• Patients must agree not to get pregnant/not to get their partner pregnant, during the trial. Consequently, patients must agree to use adequate contraception as detailed in study protocol.

Exclusion Criteria:

• Participant is unable or unwilling to participate in all scheduled visits and perform all protocol-mandated assessments.
• Has a known or suspected hypersensitivity to ilofotase alfa or any components of the formulation used.
• Body weight < 40 kilogram and > 120 kilogram.
• Patient has a history of clinically significant abnormalities or of any illness that, in the opinion of the trial investigator, might confound the results of the trial or pose an additional risk to the patient by their participation in the trial.
• NSAID use in the past 2 weeks.
• Use of corticosteroids in the past 4 weeks.
• Use of compounds intended to interfere with bone metabolism (e.g. Denosumab, Teriparatide, Romosozumab, Raloxifene) in the past 3 months.
• Use of bisphosphonates in the past 2 years.
• Participation in a drug trial within 60 days, or five times the half-life of the drug, whichever is longer, prior to administration of ilofotase alfa.
• Use of asfotase alfa in the previous 3 months. Patients will not be withheld from approved asfotase alfa if medically indicated.
• A patient who is currently pregnant or lactating.
• Use of supplements including Vitamin B6.

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: 0.8 mg/kg ilofotase alfa; Single dose administered intravenously over 1 hour	Biological: Ilofotase Alfa, 0.8 mg/kg; Biological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa; Other Names: recAP
Experimental: 3.2 mg/kg ilofotase alfa; Single dose administered intravenously over 1 hour	Biological: Ilofotase Alfa, 3.2 mg/kg; Biological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa; Other Names: recAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi)	Percent Change from BaseLine (PCBL) in PPi serum concentration is calculated for all post-dose PPi measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= [(PPi( x)-PPi(baseline))/PPi(baseline)]*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12)).	Day 1 to Day 10
Maximum Percent Change From Baseline in Pyridoxal 5'-Phosphate (PLP)	Percent Change from BaseLine (PCBL) in PLP serum concentration is calculated for all post-dose PLP measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= [(PLP( x)-PLP(baseline))/PLP(baseline)]*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12)).	Day 1 to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events (TEAEs)	Any untoward medical occurrence in a subject enrolled and treated in the clinical study regardless of its causal relationship to study drug.	Day 1 to Day 15

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Percent Change From Baseline in Alkaline Phosphatase (ALP) Activity	Percent Change from BaseLine (PCBL) in ALP Activity is calculated for all post-dose ALP measures recorded from Day 2 to Day 10. Per patient, 9 measurements were done: 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…9) is calculated: PCBL(x)= (ALP(x)-ALP(baseline))/ALP(baseline)*100, [x=1,...,9]. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(9))	Day 1 to Day 10
Maximum Percent Change From Baseline in Urine Phosphoethanolamine (PEA)	Percent Change from BaseLine (PCBL) in PEA concentration is calculated for all post-dose PEA measures recorded from Day 2 to Day 10. Per patient, 9 measurements were done: 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…9) is calculated: PCBL(x)= [(PEA( x)-PEA(baseline))/PEA(baseline)]*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(9)).	Day 1 to Day 10
Maximum Percent Change From Baseline in Pyridoxal (PL).	Percent Change from BaseLine (PCBL) in PL serum concentration is calculated for all post-dose PL measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= [(PL( x)-PL(baseline))/PL(baseline)]*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12)).	Day 1 to Day 10
Maximum Fold Change From Baseline in PL/PLP Ratio	Fold Change from BaseLine (FCBL) in PL/PLP ratio is calculated for all post-dose PL/PLP ratio measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Fold Change from BaseLine for measurement x (x=1,…12) is calculated: FCBL(x)= (PL/PLPratio( x) / PL/PLPratio(baseline)). The subject's maximum fold change from baseline is defined as the Max (FCBL(1), …, FCBL(12)).	Day 1 to Day 10
Treatment-emergent Adverse Events (TEAEs)	Any untoward medical occurrence in a patient enrolled and treated in the clinical trial regardless of its causal relationship to the trial medication.	Day 1 to Day 15

Collaborators and Investigators

• Sponsor: AM-Pharma
• Investigators: Principal Investigator: Dr Seefried, Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH, Würzburg, Germany

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 12, 2023

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 26, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Enzyme replacement therapy
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Metal Metabolism, Inborn Errors; Hypophosphatasia
• Other Study ID Numbers: AP-recAP-HPP-01-01

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