Trial Outcomes & Findings for Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP) (NCT NCT02104219)

Last Updated: 2019-04-01

Results Overview

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).

Recruitment status

COMPLETED

Target enrollment

32 participants

Primary outcome timeframe

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.

Results posted on

2019-04-01

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Retrospective Observational Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age).
Overall Study STARTED	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients Diagnosed With Juvenile-onset HPP n=32 Participants Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age).
Age, Customized	47 months STANDARD_DEVIATION 32.21 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Race/Ethnicity, Customized White	31 participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	1 participants n=5 Participants
Region of Enrollment Australia	2 participants n=5 Participants
Region of Enrollment North America	25 participants n=5 Participants
Region of Enrollment Europe	5 participants n=5 Participants
Rickets Severity Scale - RSS	1.00 units on a scale n=5 Participants
Growth Measured by Height Z-score	-0.86 Z-score n=5 Participants
Growth Measured by Weight Z-score	-0.86 Z-score n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: Patients diagnosed with juvenile-onset HPP.

Outcome measures

Outcome measures
Measure	Patients Diagnosed With Juvenile-onset HPP n=32 Participants Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age).
Radiographic Global Impression of Change - RGI-C	0.33 units on a scale Interval -0.2 to 1.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Patients Diagnosed With Juvenile-onset HPP n=32 Participants Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age).
Change in Height Z-score From Baseline to Last Assessment	-0.05 Z-score Interval -0.31 to 0.34

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Patients Diagnosed With Juvenile-onset HPP n=32 Participants Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age).
Change in Weight Z-score From Baseline to Last Assessment	0.12 Z-score Interval -0.31 to 0.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Any available data during the period of patients' aged 5 to 15 years, inclusive. Baseline is the earliest available assessment value during the period.

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Patients Diagnosed With Juvenile-onset HPP n=32 Participants Patients diagnosed with juvenile-onset HPP (ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age).
Rickets Severity Sale - RSS	0.00 units on a scale Interval 0.0 to 0.5

Adverse Events

Patients Diagnosed With Juvenile-onset HPP

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Medical Director, Clinical Development

Alexion Pharmaceuticals

Phone: 203-272-2596

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER