Hypophosphatasia (HPP)
Conditions
Keywords
Hypophosphatasia, HPP, Bone Disease, Soft Bones, Low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets, osteomalacia
Brief summary
This clinical trial studies the long term safety and efficacy of asfotase alfa in children with HPP who completed Study ENB-006-09 (NCT00952484).
Detailed description
Asfotase alfa was formerly referred to as ENB-0040 Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
Interventions
BIOLOGICALAsfotase Alfa
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Compliant and satisfactory completion of Enobia-sponsored clinical trial ENB-006-09 * Written informed consent by parent or other legal guardian prior to any study procedures being performed * Parent or other legal guardian willing to comply with study requirements
Exclusion criteria
* Clinically significant disease that precludes study participation, in the Investigator's opinion * Treatment with an investigational drug other than asfotase alfa * Enrollment in any study (other than ENB-006-09) involving an investigational drug, device, or treatment for HPP * Prior treatment with bisphosphonates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal Radiograph Evaluation Using a Qualitative Radiographic Global Impression of Change (RGI-C) Scale Compared to Baseline (Pre-treatment) in Study ENB-006-09. | At least 72 months of treatment with asfotase alfa | Evaluation of radiographic change in rickets severity (as assessed by skeletal radiographs of the hands/wrists and knees) from the Baseline of Study ENB-006-09 (NCT00952484) to the End of Study (EOS) visit in Study ENB-008-10 using an ordinal RGI-C scale score. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP associated rickets) to +3 (indicative of complete or near complete healing of HPP associated rickets). The time points will be pre-treatment (Baseline from Study ENB-006-09) to the last radiographic assessment in Study ENB-008-10, which represents at least 72 months of treatment. |
Countries
Canada, United States
Participant flow
Recruitment details
The main criteria for inclusion in Study ENB-006-09 were patients ages 5 to 12 years inclusive, with open growth plates at time of study entry and a documented diagnosis of HPP. To enter the extension, Study ENB-008-10, patients had to successfully complete Study ENB-006-09 and provide consent.
Participants by arm
| Arm | Count |
|---|---|
| 2 mg/kg Asfotase Alfa Dose group shown is as per patient's randomization in Study ENB-006-09 | 6 |
| 3 mg/kg Asfotase Alfa Dose group shown is as per patient's randomization in Study ENB-006-09 | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | 2 mg/kg Asfotase Alfa | 3 mg/kg Asfotase Alfa | Total |
|---|---|---|---|
| Age at Onset of Hypophosphatasia Symptoms | 10.8 Months STANDARD_DEVIATION 8.66 | 11.5 Months STANDARD_DEVIATION 5.54 | 11.2 Months STANDARD_DEVIATION 6.94 |
| Age, Continuous | 8.4 years STANDARD_DEVIATION 2.21 | 9.0 years STANDARD_DEVIATION 2.51 | 8.7 years STANDARD_DEVIATION 2.27 |
| Age, Customized Age Group at Enrollment: 12 to 17 Years; % | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized Age Group at Enrollment: 2 to 11 Years; % | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hypophosphatasia Phenotype Infantile (< 6 months) | 3 Participants | 1 Participants | 4 Participants |
| Hypophosphatasia Phenotype Juvenile (≥ 6 months to < 18 yrs) | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment Canada | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
| Tanner Stage 1 | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 12 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 12 |
Outcome results
Primary
Skeletal Radiograph Evaluation Using a Qualitative Radiographic Global Impression of Change (RGI-C) Scale Compared to Baseline (Pre-treatment) in Study ENB-006-09.
Evaluation of radiographic change in rickets severity (as assessed by skeletal radiographs of the hands/wrists and knees) from the Baseline of Study ENB-006-09 (NCT00952484) to the End of Study (EOS) visit in Study ENB-008-10 using an ordinal RGI-C scale score. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP associated rickets) to +3 (indicative of complete or near complete healing of HPP associated rickets). The time points will be pre-treatment (Baseline from Study ENB-006-09) to the last radiographic assessment in Study ENB-008-10, which represents at least 72 months of treatment.
Time frame: At least 72 months of treatment with asfotase alfa
Population: Each visit in Study ENB-008-10 was calculated relative to the start of exposure to asfotase alfa in Study ENB-006-09 (NCT00952484); 24 weeks are added to each visit in Study ENB-008-10. Results shown are for the last assessment in Study ENB-008-10 and represent at least 72 months of treatment with asfotase alfa.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa Combined | Skeletal Radiograph Evaluation Using a Qualitative Radiographic Global Impression of Change (RGI-C) Scale Compared to Baseline (Pre-treatment) in Study ENB-006-09. | 2.83 units on a scale |
Comparison: Change is relative to Baseline in Study ENB-006-09 (NCT00952484). The RGI-C score represents evaluations of skeletal X-rays at each post-treatment study timepoint in Study ENB-008-10 compared with pre-treatment X-rays from Study ENB-006-09, using an ordinal scale. Therefore, no Baseline data for RGI-C are available.p-value: 0.0005Wilcoxon signed-rank test