Trial Outcomes & Findings for Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia (NCT NCT05890794)

NCT ID: NCT05890794

Last Updated: 2025-02-27

Results Overview

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)).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Day 1 to Day 10

Results posted on

2025-02-27

Participant Flow

12 patients were enrolled, screened and randomized (6 to the 0.8 mg ilofotase alfa dose group, 6 to the 3.2 mg ilofotase alfa dose group)

Participant milestones

Participant milestones
Measure
0.8 mg/kg Ilofotase Alfa
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall Study
STARTED
6
6
Overall Study
COMPLETED
6
6
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Total
n=12 Participants
Total of all reporting groups
Age, Continuous
49.5 years
n=6 Participants
51.0 years
n=6 Participants
51.0 years
n=12 Participants
Sex: Female, Male
Female
3 Participants
n=6 Participants
5 Participants
n=6 Participants
8 Participants
n=12 Participants
Sex: Female, Male
Male
3 Participants
n=6 Participants
1 Participants
n=6 Participants
4 Participants
n=12 Participants
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Day 1 to Day 10

Population: All randomized patients.

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)).

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi)
-36.46 percent change
Standard Deviation 11.502
-77.31 percent change
Standard Deviation 16.113
-56.88 percent change
Standard Deviation 25.165

PRIMARY outcome

Timeframe: Day 1 to Day 10

Population: All randomized patients.

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)).

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Maximum Percent Change From Baseline in Pyridoxal 5'-Phosphate (PLP)
-34.68 percent change
Standard Deviation 8.898
-65.56 percent change
Standard Deviation 6.559
-50.12 percent change
Standard Deviation 17.768

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 10

Population: All randomized patients.

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))

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Maximum Percent Change From Baseline in Alkaline Phosphatase (ALP) Activity
2685.57 percent change
Standard Deviation 1492.991
7021.23 percent change
Standard Deviation 2063.878
4853.40 percent change
Standard Deviation 2841.847

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 10

Population: All randomized patients.

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)).

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Maximum Percent Change From Baseline in Urine Phosphoethanolamine (PEA)
-28.58 percent change
Standard Deviation 15.161
-51.82 percent change
Standard Deviation 19.614
-40.20 percent change
Standard Deviation 20.573

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 10

Population: All randomized patients.

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)).

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Maximum Percent Change From Baseline in Pyridoxal (PL).
409.76 percent change
Standard Deviation 138.504
222.33 percent change
Standard Deviation 91.332
316.05 percent change
Standard Deviation 148.635

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 10

Population: All randomized patients.

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)).

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Maximum Fold Change From Baseline in PL/PLP Ratio
6.9145 fold change
Standard Deviation 1.83957
7.8062 fold change
Standard Deviation 2.70554
7.3604 fold change
Standard Deviation 2.25440

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 15

Population: All patients who received trial medication were included in the population for the safety analysis.

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

Outcome measures

Outcome measures
Measure
0.8 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 Participants
Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 Participants
Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa
Treatment-emergent Adverse Events (TEAEs)
1 Participants
3 Participants
4 Participants

Adverse Events

0.8 mg/kg Ilofotase Alfa

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

3.2 mg/kg Ilofotase Alfa

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Overall

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
0.8 mg/kg Ilofotase Alfa
n=6 participants at risk
Single dose administered intravenously over 1 hour Ilofotase Alfa, 0.8 mg/kg: Biological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa
3.2 mg/kg Ilofotase Alfa
n=6 participants at risk
Single dose administered intravenously over 1 hour Ilofotase Alfa, 3.2 mg/kg: Biological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa
Overall
n=12 participants at risk
Single dose administered intravenously over 1 hour Ilofotase Alfa, 0.8 or 3.2 mg/kg: Biological: single 1-hour intravenous infusion of 0.8 or 3.2 mg/kg ilofotase alfa
Nervous system disorders
Dysgeusia
0.00%
0/6 • Day 1 to Day 15
33.3%
2/6 • Number of events 2 • Day 1 to Day 15
16.7%
2/12 • Number of events 2 • Day 1 to Day 15
Nervous system disorders
Headache
0.00%
0/6 • Day 1 to Day 15
16.7%
1/6 • Number of events 1 • Day 1 to Day 15
8.3%
1/12 • Number of events 1 • Day 1 to Day 15
Nervous system disorders
Restless arm syndrome
0.00%
0/6 • Day 1 to Day 15
16.7%
1/6 • Number of events 1 • Day 1 to Day 15
8.3%
1/12 • Number of events 1 • Day 1 to Day 15
Nervous system disorders
Restless legs syndrome
0.00%
0/6 • Day 1 to Day 15
16.7%
1/6 • Number of events 1 • Day 1 to Day 15
8.3%
1/12 • Number of events 1 • Day 1 to Day 15
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/6 • Day 1 to Day 15
16.7%
1/6 • Number of events 1 • Day 1 to Day 15
8.3%
1/12 • Number of events 1 • Day 1 to Day 15
Gastrointestinal disorders
Nausea
0.00%
0/6 • Day 1 to Day 15
16.7%
1/6 • Number of events 1 • Day 1 to Day 15
8.3%
1/12 • Number of events 1 • Day 1 to Day 15
Musculoskeletal and connective tissue disorders
Pain in extremity
16.7%
1/6 • Number of events 1 • Day 1 to Day 15
0.00%
0/6 • Day 1 to Day 15
8.3%
1/12 • Number of events 1 • Day 1 to Day 15

Additional Information

AM-Pharma Office

AM-Pharma

Phone: 31 (0)30 228 92 22

Results disclosure agreements

  • Principal investigator is a sponsor employee The PI may publish the study results but must submit the publication to the sponsor for review at least 60 days prior to publication. The sponsor may request changes/removals of sponsor information. The PI should remove such information if the correct presentation of the results is still ensured. The PI must consider the sponsor's other comments but must not adopt them. If publication could affect the patentability of the invention, the sponsor may request an additional period of up to 120 days.
  • Publication restrictions are in place

Restriction type: OTHER