Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia

NCT05890794 | Completed Phase 1 Results

• 1 other identifier: AP-recAP-HPP-01-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypophosphatasia

Keywords

Enzyme replacement therapy

Outcome Measures

Primary Outcomes (2)

• 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

Other Outcomes (5)

• Maximum Percent Change From Baseline in Alkaline Phosphatase (ALP) Activity

  Day 1 to Day 10

• Maximum Percent Change From Baseline in Urine Phosphoethanolamine (PEA)

  Day 1 to Day 10

• Maximum Percent Change From Baseline in Pyridoxal (PL).

  Day 1 to Day 10

Study Arms (2)

0.8 mg/kg ilofotase alfa

EXPERIMENTAL

Single dose administered intravenously over 1 hour

Biological: Ilofotase Alfa, 0.8 mg/kg

3.2 mg/kg ilofotase alfa

EXPERIMENTAL

Single dose administered intravenously over 1 hour

Biological: Ilofotase Alfa, 3.2 mg/kg

Interventions

Ilofotase Alfa, 0.8 mg/kg BIOLOGICAL

Biological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa

Also known as: recAP

0.8 mg/kg ilofotase alfa

Ilofotase Alfa, 3.2 mg/kg BIOLOGICAL

Biological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa

Also known as: recAP

3.2 mg/kg ilofotase alfa

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AM-Pharma: lead

Study Sites (1)

Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH

Würzburg, 97074, Germany

Location

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: AM-Pharma Office
• Organization: AM-Pharma

office@am-pharma.com

31 (0)30 228 92 22

Study Officials

• Dr Seefried

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Trial is masked for received dose; type of drug received is open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2 doses will be compared

Study Record Dates

• First Submitted: May 10, 2023
• First Posted: June 6, 2023
• Study Start: May 15, 2023
• Primary Completion: July 7, 2023
• Study Completion: July 12, 2023
• Last Updated: February 27, 2025
• Results First Posted: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)