Phase 3
N=69
Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)
Hypophosphatasia
Bottom Line
View on ClinicalTrials.gov: NCT01176266 ↗Enrolled (actual)
69
Serious AEs
72.5%
Results posted
Feb 2018
Primary outcome: Primary: Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) — 2.00 scores on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- asfotase alfa (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Primary completion
- Sep 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) |
2.33 | — |
| PRIMARY Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa |
69 | — |
| SECONDARY Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) |
2.33 | — |
| SECONDARY Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312) |
0.81 | — |
| SECONDARY Effect of Asfotase Alfa Treatment on Respiratory Function |
45; 43; 11; 6; 1; 2 | — |
| SECONDARY Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value |
0.5 | — |
| SECONDARY Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value |
1.0 | — |
| SECONDARY Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value |
-2.460 | — |
| SECONDARY Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value |
-395.40 | — |
| SECONDARY Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value |
0.70 | — |
| SECONDARY Effect of Asfotase Alfa Treatment on Tooth Loss |
42 | — |
| SECONDARY Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast) |
48.1 | — |
| SECONDARY Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax) |
14.9 | — |
| SECONDARY Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax) |
1794 | — |
| SECONDARY Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt) |
66042 | — |
Summary
This clinical trial was conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study was to test the safety and efficacy of a study drug called asfotase alfa (human recombinant tissue non-specific alkaline phosphate fusion protein) to see what effects it has on patients 5 years of age or less with HPP.
Eligibility Criteria
Inclusion Criteria
Patients must meet all of the following criteria for enrollment in this study:
- Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures. Where appropriate and required by local regulations, patient assent should also be provided prior to any study procedures being performed.
- Documented diagnosis of HPP as indicated by:
- Total serum alkaline phosphatase (ALP) below the lower limit of normal for age NOTE: Historical values for ALP may be used to determine patient eligibility.
- Plasma pyridoxal-5'-phosphate (PLP) above the upper limit of normal (unless patient is receiving pyridoxine for seizures) NOTE: Historical values for PLP may be used to determine patient eligibility.
- Radiographic evidence of HPP at screening, characterized by:
- Flared and frayed metaphyses, and
- Severe, generalized osteopenia, and
- Widened growth plates, and
- Areas of radiolucency or sclerosis
- Two or more of the following HPP-related findings:
- History or presence of: i) Nontraumatic post-natal fracture or ii) Delayed fracture healing
- Nephrocalcinosis or history of elevated serum calcium
- Functional craniosynostosis
- Respiratory compromise or rachitic chest deformity
- Vitamin B6-responsive seizures
- Failure to thrive
- Onset of symptoms prior to 6 months of age
- Chronological age or adjusted age for premature infants born ≤ 37 weeks gestation of ≤ 5 years
- Otherwise medically stable in the opinion of the Investigator and/or Sponsor
Exclusion criteria
Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria:
- Clinically significant disease that precludes study participation, in the opinion of the Investigator and/or Sponsor
- Serum calcium or phosphate levels below the normal range
- Current evidence of treatable form of rickets
- Prior treatment with bisphosphonates
- Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment
- Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
- Intolerance to the investigational product (IP) or any of its excipients
- Previous participation in the same study
- Family relative of the Investigator
Data sourced from ClinicalTrials.gov (NCT01176266). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.