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Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP)

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ClinicalTrials.gov Identifier: NCT02104219
Recruitment Status : Completed
First Posted : April 4, 2014
Results First Posted : December 18, 2015
Last Update Posted : December 18, 2015
Sponsor:
Information provided by (Responsible Party):
Alexion Pharma GmbH

Study Type Observational
Study Design Time Perspective: Retrospective
Condition Hypophosphatasia (HPP)
Enrollment 32
Recruitment Details Patients were enrolled between March 2014 and September 2014. Fifty-four patients were screened and 32 patients were enrolled at 15 centers across the United States, Canada, Australia, Turkey, The Netherlands, and the United Kingdom.
Pre-assignment Details  
Arm/Group Title Retrospective Observational
Hide Arm/Group Description Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
Period Title: Overall Study
Started 32
Completed 32
Not Completed 0
Arm/Group Title Patients Diagnosed With Juvenile-onset HPP
Hide Arm/Group Description Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 32 participants
47  (32.21)
[1]
Measure Description: Age at diagnosis
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
10
  31.3%
Male
22
  68.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants
White 31
Unknown or Not Reported 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants
Australia 2
North America 25
Europe 5
Rickets Severity Scale - RSS   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 32 participants
1.00
(0.00 to 1.50)
[1]
Measure Description: The RSS is a 10-point scale, developed for nutritional rickets, that evaluates the degree of metaphyseal cupping and fraying and the proportion of growth plate affected (10 points = severe cupping/fraying, 0 points = absence of cupping/fraying).
Growth Measured by Height Z-score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Z-score
Number Analyzed 32 participants
-0.86
(-1.57 to -0.62)
[1]
Measure Description: The Z-score indicates the number of standard deviations away from the mean 0. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
Growth Measured by Weight Z-score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Z-score
Number Analyzed 32 participants
-0.86
(-1.45 to -0.49)
[1]
Measure Description: The Z-score indicates the number of standard deviations away from the mean 0. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
1.Primary Outcome
Title Radiographic Global Impression of Change - RGI-C
Hide Description The RGI-C scale is a 7-point ordinal scale that is used to evaluate musculoskeletal characteristics of HPP (eg, metaphyseal fraying, demineralization of distal metaphyses). The scores range from -3 (severe worsening) to +3 (complete or near-complete healing).
Time Frame Between Baseline (earliest available, complete, and readable x-ray set) and all available, readable post-Baseline x-ray sets during the period of patients' aged 5 to 15 years, inclusive.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients diagnosed with juvenile-onset HPP.
Arm/Group Title Patients Diagnosed With Juvenile-onset HPP
Hide Arm/Group Description:
Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
Overall Number of Participants Analyzed 32
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
0.33
(-0.2 to 1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patients Diagnosed With Juvenile-onset HPP
Comments Pairs of radiographs were centrally evaluated by 3 independent, blinded pediatric radiologists trained in the assessment of the skeletal manifestations of HPP. The mean RGI-C score across the 3 radiologists was calculated and served as the patient’s RGI-C score for a specific time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0755
Comments The p-value is based on a nonparametric sign test used to determine whether the median RGI-C score differs from 0 for each time interval. No multiple comparisons or multiplicity adjustments were conducted.
Method Sign test
Comments [Not Specified]
2.Secondary Outcome
Title Change in Height Z-score From Baseline to Last Assessment
Hide Description Height measurements were assigned to Z-scores which were calculated using the Centers for Disease Control and Prevention (CDC) 2000 growth charts and methodology. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
Time Frame Any available growth data during the period of patients’ aged 5 to 15 years, inclusive. Baseline is the earliest available assessment while post baselines are time points after Baseline during the defined age period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patients Diagnosed With Juvenile-onset HPP
Hide Arm/Group Description:
Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
Overall Number of Participants Analyzed 32
Median (Inter-Quartile Range)
Unit of Measure: Z-score
-0.05
(-0.31 to 0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patients Diagnosed With Juvenile-onset HPP
Comments The earliest documented height measurement that was abstracted within the period from 5 to 15 years of age, inclusive, was defined as the baseline height. Height measurements were assigned to Z-scores calculated using Centers for Disease Control and Prevention 2000 growth charts and methodology. Changes in height Z-score from Baseline were computed by subtracting baseline height Z-score from post baseline height Z-scores. The post baseline time points were grouped by time intervals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6344
Comments The p-value is based on a nonparametric sign test used to determine whether the median change in height Z-score from baseline to last assessment differs from 0. No multiple comparisons or multiplicity adjustments were conducted.
Method Sign test
Comments [Not Specified]
3.Secondary Outcome
Title Change in Weight Z-score From Baseline to Last Assessment
Hide Description Weight measurements were assigned a Z-score which was calculated using the Centers for Disease Control and Prevention (CDC) 2000 growth charts and methodology. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
Time Frame Any available growth data during the period of patients’ aged 5 to 15 years, inclusive. Baseline is the earliest available assessment while Post baselines are time points after Baseline during the defined age period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who met all of the inclusion and none of the exclusion criteria were defined as the enrolled population, which was also the analysis population.
Arm/Group Title Patients Diagnosed With Juvenile-onset HPP
Hide Arm/Group Description:
Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
Overall Number of Participants Analyzed 32
Median (Inter-Quartile Range)
Unit of Measure: Z-score
0.12
(-0.31 to 0.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patients Diagnosed With Juvenile-onset HPP
Comments The earliest documented weight measurement that was abstracted within the period from 5 to 15 years of age, inclusive, was defined as the baseline weight. Weight measurements were assigned to Z-scores calculated using Centers for Disease Control and Prevention 2000 growth charts and methodology. Changes in weight Z-score from Baseline were computed by subtracting baseline weight Z-score from post baseline weight Z-scores. The post baseline time points were grouped by time intervals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4520
Comments The p-value is based on a nonparametric sign test used to determine whether the median change in weight Z-score from baseline to last assessment differs from 0. No multiple comparisons or multiplicity adjustments were conducted.
Method Sign test
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Rickets Severity Sale - RSS
Hide Description The RSS is a 10-point scale, developed for nutritional rickets, that evaluates the degree of metaphyseal cupping and fraying and the proportion of growth plate affected (10 points = severe cupping/fraying, 0 points = absence of cupping/fraying).
Time Frame Any available data during the period of patients’ aged 5 to 15 years, inclusive. Baseline is the earliest available assessment value during the period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who met all of the inclusion and none of the exclusion criteria were defined as the enrolled population, which was also the analysis population.
Arm/Group Title Patients Diagnosed With Juvenile-onset HPP
Hide Arm/Group Description:
Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
Overall Number of Participants Analyzed 32
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
0.00
(0.00 to 0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patients Diagnosed With Juvenile-onset HPP
Comments The Baseline x-ray set defined for RGI-C, which was compared with its subsequent x-ray sets, was also used as the Baseline x-ray set for the RSS reading. Changes from Baseline were computed based on this baseline RSS score, and postbaseline time points were grouped by intervals of time from Baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4545
Comments The p-value is based on a nonparametric sign test used to determine whether change from baseline in the median RSS score differs from 0 for each time interval. No multiple comparisons or multiplicity adjustments were conducted.
Method Sign test
Comments [Not Specified]
Time Frame No adverse event data were collected during this retrospective noninterventional study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Patients Diagnosed With Juvenile-onset HPP
Hide Arm/Group Description Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to < 18 years of age).
All-Cause Mortality
Patients Diagnosed With Juvenile-onset HPP
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Patients Diagnosed With Juvenile-onset HPP
Affected / at Risk (%)
Total   0/0 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Patients Diagnosed With Juvenile-onset HPP
Affected / at Risk (%)
Total   0/0 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Participation in a multicenter study involves a commitment to publish the data from the study in a cooperative publication prior to release of study results on an individual basis. Therefore, PIs are subject to certain disclosure and publication limitations.
Results Point of Contact
Name/Title: Senior Medical Director, Clinical Development
Organization: Alexion Pharmaceuticals
Phone: 203-272-2596
Responsible Party: Alexion Pharma GmbH
ClinicalTrials.gov Identifier: NCT02104219     History of Changes
Obsolete Identifiers: NCT02104206
Other Study ID Numbers: ALX-HPP-502
First Submitted: March 25, 2014
First Posted: April 4, 2014
Results First Submitted: August 25, 2015
Results First Posted: December 18, 2015
Last Update Posted: December 18, 2015