HypophosphatasiaPhase 1/2NCT05890794
Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia
A Phase 1/2 study testing Ilofotase Alfa, 0.8 mg/kg and Ilofotase Alfa, 3.2 mg/kg in people with Hypophosphatasia, run by AM-Pharma at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- Ilofotase Alfa, 0.8 mg/kg and Ilofotase Alfa, 3.2 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteGermany
- Study dates
- 15 May 2023to 12 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH
Würzburg, 97074
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypophosphatasia
- Being tested
- Ilofotase Alfa, 0.8 mg/kg, Ilofotase Alfa, 3.2 mg/kg
- Keywords
- Enzyme replacement therapy
- Medical subject headings
- Hypophosphatasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ilofotase Alfa, 0.8 mg/kgBiological
Also called recAP
Biological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
Ilofotase Alfa, 3.2 mg/kgBiological
Also called recAP
Biological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
| Study group | Role | What they receive |
|---|---|---|
| 0.8 mg/kg ilofotase alfa | Experimental | Single dose administered intravenously over 1 hour Receives: Biological: Ilofotase Alfa, 0.8 mg/kg |
| 3.2 mg/kg ilofotase alfa | Experimental | Single dose administered intravenously over 1 hour Receives: Biological: Ilofotase Alfa, 3.2 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)).
Measured: 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)).
Measured: Day 1 to Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2023
- Study start15 May 2023
- Primary completion7 Jul 2023
- Study completion12 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypophosphatasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2 doses will be compared
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- AM-Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr Seefried, Principal investigator, Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH, Würzburg, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05890794
- Sponsor's protocol ID
- AP-recAP-HPP-01-01
- Status last verified
- Feb 2025
- First submitted
- 10 May 2023
- Last updated
- 27 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Seefried L, Bernholz J, Kraan M, Nitschke Y, Rutsch F, Mallek M, Kleinert S, Genest F. A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia. J Bone Miner Res. 2026 Mar 2;41(3):231-241. doi: 10.1093/jbmr/zjaf185.
PubMed 41378916
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label Pilot Trial to Evaluate the Effects of Ilofotase Alfa on Biomarkers in Adult Patients With Hypophosphatasia
- ClinicalTrials.gov ID
- NCT05890794
- Acronym / sponsor ID
- AP-recAP-HPP-01-01
- Conditions
- Hypophosphatasia
- Keywords
- Enzyme replacement therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AM-PharmaIndustry (pharma, biotech, devices)
- Study start
- 15 May 2023 (actual)
- Primary completion
- 7 Jul 2023 (actual)
- Study completion
- 12 Jul 2023 (actual)
- First posted
- 6 Jun 2023 (actual)
- Results
- Posted 27 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 2 doses will be compared
| Arm | Type | Receives |
|---|---|---|
| 0.8 mg/kg ilofotase alfa | Experimental | Biological: Ilofotase Alfa, 0.8 mg/kgSingle dose administered intravenously over 1 hour |
| 3.2 mg/kg ilofotase alfa | Experimental | Biological: Ilofotase Alfa, 3.2 mg/kgSingle dose administered intravenously over 1 hour |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ilofotase Alfa, 0.8 mg/kgAlso: recAPBiological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa | Biological | 0.8 mg/kg ilofotase alfa |
| Ilofotase Alfa, 3.2 mg/kgAlso: recAPBiological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa | Biological | 3.2 mg/kg ilofotase alfa |
Primary outcome
Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi)
Time frame: Day 1 to Day 10
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)).
Maximum Percent Change From Baseline in Pyridoxal 5'-Phosphate (PLP)
Time frame: Day 1 to Day 10
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)).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41378916Seefried L, Bernholz J, Kraan M, Nitschke Y, Rutsch F, Mallek M, Kleinert S, Genest F. A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia. J Bone Miner Res. 2026 Mar 2;41(3):231-241. doi: 10.1093/jbmr/zjaf185.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Seefried principal investigator
Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH, Würzburg, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ilofotase Alfa, 0.8 mg/kg and Ilofotase Alfa, 3.2 mg/kg in people with Hypophosphatasia, run by AM-Pharma at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi) (time frame: Day 1 to Day 10). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05890794, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.