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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01176266




Registration number
NCT01176266
Ethics application status
Date submitted
29/07/2010
Date registered
5/08/2010
Date last updated
13/03/2019

Titles & IDs
Public title
Open-Label Study of Asfotase Alfa in Infants and Children = 5 Years of Age With Hypophosphatasia (HPP)
Scientific title
An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) in Infants and Children = 5 Years of Age With Hypophosphatasia (HPP)
Secondary ID [1] 0 0
ENB-010-10
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypophosphatasia 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Asfotase alfa - A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP)
Timepoint [1] 0 0
From Baseline to Week 24
Primary outcome [2] 0 0
Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa
Timepoint [2] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [1] 0 0
Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP)
Timepoint [1] 0 0
Up to 72 Months or regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [2] 0 0
Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312)
Timepoint [2] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [3] 0 0
Effect of Asfotase Alfa Treatment on Respiratory Function
Timepoint [3] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [4] 0 0
Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value
Timepoint [4] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [5] 0 0
Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value
Timepoint [5] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [6] 0 0
Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value
Timepoint [6] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [7] 0 0
Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value
Timepoint [7] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [8] 0 0
Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value
Timepoint [8] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [9] 0 0
Effect of Asfotase Alfa Treatment on Tooth Loss
Timepoint [9] 0 0
Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Secondary outcome [10] 0 0
Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast)
Timepoint [10] 0 0
PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Secondary outcome [11] 0 0
Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax)
Timepoint [11] 0 0
PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Secondary outcome [12] 0 0
Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax)
Timepoint [12] 0 0
PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Secondary outcome [13] 0 0
Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt)
Timepoint [13] 0 0
PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose

Eligibility
Key inclusion criteria
Patients must meet all of the following criteria for enrollment in this study:

1. 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.
2. Documented diagnosis of HPP as indicated by:

1. 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.
2. 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.
3. 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
4. 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
3. Onset of symptoms prior to 6 months of age
4. Chronological age or adjusted age for premature infants born = 37 weeks gestation of = 5 years
5. Otherwise medically stable in the opinion of the Investigator and/or Sponsor
Minimum age
1 Minute
Maximum age
5 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria:

1. Clinically significant disease that precludes study participation, in the opinion of the Investigator and/or Sponsor
2. Serum calcium or phosphate levels below the normal range
3. Current evidence of treatable form of rickets
4. Prior treatment with bisphosphonates
5. Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment
6. Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
7. Intolerance to the investigational product (IP) or any of its excipients
8. Previous participation in the same study
9. Family relative of the Investigator

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2016
Sample size
Target
Accrual to date
Final
69
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [2] 0 0
Royal Children'S Hospital Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Canada
State/province [4] 0 0
Manitoba
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
France
State/province [6] 0 0
Toulouse
Country [7] 0 0
Germany
State/province [7] 0 0
Würzburg
Country [8] 0 0
Italy
State/province [8] 0 0
Genova
Country [9] 0 0
Italy
State/province [9] 0 0
Roma
Country [10] 0 0
Japan
State/province [10] 0 0
Fukuoka
Country [11] 0 0
Japan
State/province [11] 0 0
Ishikawa
Country [12] 0 0
Japan
State/province [12] 0 0
Kanagawa
Country [13] 0 0
Japan
State/province [13] 0 0
Tokyo
Country [14] 0 0
Japan
State/province [14] 0 0
Saitama
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Moscow
Country [16] 0 0
Saudi Arabia
State/province [16] 0 0
Riyadh
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid
Country [18] 0 0
Turkey
State/province [18] 0 0
Bursa
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Birmingham
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Manchester
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT01176266
Trial related presentations / publications
Padidela R, Yates R, Benscoter D, McPhail G, Chan E, Nichani J, Mughal MZ, Myer C 4th, Narayan O, Nissenbaum C, Wilkinson S, Zhou S, Saal HM. Characterization of tracheobronchomalacia in infants with hypophosphatasia. Orphanet J Rare Dis. 2020 Aug 6;15(1):204. doi: 10.1186/s13023-020-01483-9.
Hofmann CE, Harmatz P, Vockley J, Hogler W, Nakayama H, Bishop N, Martos-Moreno GA, Moseley S, Fujita KP, Liese J, Rockman-Greenberg C; ENB-010-10 Study Group. Efficacy and Safety of Asfotase Alfa in Infants and Young Children With Hypophosphatasia: A Phase 2 Open-Label Study. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2735-2747. doi: 10.1210/jc.2018-02335.
Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, Thompson DD, Bishop N, Hofmann C. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01176266