NCT05890794

Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia

Completed Phase 1, PHASE2 Results posted Last updated 27 February 2025

What this trial tests

Phase 1, PHASE2 trial testing Ilofotase Alfa, 0.8 mg/kg in Hypophosphatasia in 12 participants. Completed in 12 July 2023.

Timeline

15 May 2023

Primary endpoint
7 July 2023

12 July 2023

Quick facts

Lead sponsor	AM-Pharma
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	12
Start date	15 May 2023
Primary completion	7 July 2023
Estimated completion	12 July 2023
Sites	1 location across Germany

Drugs / interventions tested

• Ilofotase Alfa, 0.8 mg/kg — full drug profile →
• Ilofotase Alfa, 3.2 mg/kg — full drug profile →

Conditions studied

• Hypophosphatasia — all drugs for Hypophosphatasia →

Sponsor

AM-Pharma — full company profile →

Who can join

Adults 18 to 85, any sex, with Hypophosphatasia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi) Primary · 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)).

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	-36.46	± 11.502
3.2 mg/kg Ilofotase Alfa	-77.31	± 16.113
Overall	-56.88	± 25.165

Maximum Percent Change From Baseline in Pyridoxal 5'-Phosphate (PLP) Primary · 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)).

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	-34.68	± 8.898
3.2 mg/kg Ilofotase Alfa	-65.56	± 6.559
Overall	-50.12	± 17.768

Maximum Percent Change From Baseline in Alkaline Phosphatase (ALP) Activity Secondary · Day 1 to Day 10

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))

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	2685.57	± 1492.991
3.2 mg/kg Ilofotase Alfa	7021.23	± 2063.878
Overall	4853.40	± 2841.847

Maximum Percent Change From Baseline in Urine Phosphoethanolamine (PEA) Secondary · Day 1 to Day 10

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)).

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	-28.58	± 15.161
3.2 mg/kg Ilofotase Alfa	-51.82	± 19.614
Overall	-40.20	± 20.573

Maximum Percent Change From Baseline in Pyridoxal (PL). Secondary · Day 1 to Day 10

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)).

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	409.76	± 138.504
3.2 mg/kg Ilofotase Alfa	222.33	± 91.332
Overall	316.05	± 148.635

Maximum Fold Change From Baseline in PL/PLP Ratio Secondary · Day 1 to Day 10

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)).

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	6.9145	± 1.83957
3.2 mg/kg Ilofotase Alfa	7.8062	± 2.70554
Overall	7.3604	± 2.25440

Treatment-emergent Adverse Events (TEAEs) Secondary · Day 1 to Day 15

Any untoward medical occurrence in a patient enrolled and treated in the clinical trial regardless of its causal relationship to the trial medication.

Group	Value	95% CI
0.8 mg/kg Ilofotase Alfa	1
3.2 mg/kg Ilofotase Alfa	3
Overall	4

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 to Day 15. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

0.8 mg/kg Ilofotase Alfa

Serious: 0/6 (0%)

Deaths: 0/6

3.2 mg/kg Ilofotase Alfa

Serious: 0/6 (0%)

Deaths: 0/6

Overall

Serious: 0/12 (0%)

Deaths: 0/12

Other adverse events (7 terms — click to expand)

Reaction	System	0.8 mg/kg Ilofotase Alfa	3.2 mg/kg Ilofotase Alfa	Overall
Dysgeusia	Nervous system disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Restless arm syndrome	Nervous system disorders	—	—	—
Restless legs syndrome	Nervous system disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—

Data from ClinicalTrials.gov NCT05890794 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Diagnosis and Treatment of Hypophosphatasia.
   Seefried L, Genest F, Hofmann C, Brandi ML, et al · · 2025 · cited 8× · PMID 40047955 · DOI 10.1007/s00223-025-01356-y
2. A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia.
   Seefried L, Bernholz J, Kraan M, Nitschke Y, et al · · 2026 · PMID 41378916 · DOI 10.1093/jbmr/zjaf185