UMIN-CTR Clinical Trial

Basic information
Public title	SEARCH FOR CLINICAL MARKERS REFLECTING DISEASE BURDEN OF PERINATAL AND INFANTILE HYPOPHOSPHATASIA
Acronym	Marker study in patients with HPP
Scientific Title	SEARCH FOR CLINICAL MARKERS REFLECTING DISEASE BURDEN OF PERINATAL AND INFANTILE HYPOPHOSPHATASIA
Scientific Title:Acronym	Marker study in patients with HPP
Region	Japan

Condition
Condition	hypophosphatasia
Classification by specialty	Endocrinology and Metabolism Pediatrics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The primary objectives of this study are to investigate the following matters in perinatal lethal/non-lethal and infantile HPP in clinical course: >To identify candidate predictive markers that could correlate with the disease burden of bone manifestation in HPP >To investigate bone calcification and bone quality by BMD, BMC and bone metabolism markers other than RSS and RGI-C, regardless of therapeutic intervention including Asfotase alfa treatment
Basic objectives2	Others
Basic objectives -Others	The secondary objectives of this study are to investigate the following matters in perinatal lethal/non-lethal HPP and infantile HPP in clinical course: >To search for candidate factors to affect motor functions development >To investigate association of the extent of whole body bone calcification with dental manifestations >To investigate disease burden of developmental/mental delay, and to search for the factors associated with developmental/mental delay
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	>Evaluation of bone based on radiographs using Rickets Severity Scale (RSS) and modified Radiographic global impression of change(mRGI-C) as a validated scale of HPP(0, 12, 24, 48, 72, 96week) >Time until intervention with artificial respiratory therapy becomes necessary in the patients who have not received artificial respiratory therapy at the beginning of the observation period (0, 12, 24, 48, 72, 96week) >In the patients who have necessitated artificial respiratory therapy at the beginning of the observation period or during the observation period, evaluation will be made based on the status of artificial respirator, respiratory support time (including the duration of the use of artificial respirator or the duration of oxygen inhalation), frequency of ventilation with artificial respirator or oxygen flow rate, pressure of artificial respirator, and fraction of inspiratory oxygen (FiO2). (0, 12, 24, 48, 72, 96week) >Body weight, height, arm span, head circumference and chest circumference will be determined and physical development will be examined and evaluated. (0, 12, 24, 48, 72, 96week) >Intellectual and motor development will be evaluated using Kyoto Scale of Psychological Development (K scale). (48, 96week) >The clinical course of HPP in teeth will be examined and evaluated on the basis of the clinical findings such as the number, time and site of teeth lost, depth of the periodontal pockets, periodontal bleeding, tooth mobility and dental formula, and imaging evaluation of morphological abnormalities of teeth and dental age on radiographs. (48, 72, 96week) >Gross motor function test will be conducted using Denver IIgross motor development scale. (24, 48, 72, 96week) >Hearing test will be conducted using the auditory brain stem response (ABR) to evaluate the status of impaired hearing. (0, 24week)
Key secondary outcomes	Health Outcomes >ADL will be evaluated using PedsQL and CHAQ. (96week) Biomarkers >PLP, PL (0 or cord blood sample, 12, 24, 48, 72, 96week) and metabolites detected by metabolome technology in plasma 0 or cord blood, 12, 48week will be determined to evaluate the usefulness as metabolic markers >P1NP, CTX, Sclerostin, FGF23 and factors related with bone metabolism tested by multi-plex analysisin serum will be determined as bone metabolism markers to investigate the usefulness as markers reflecting bone quality (0 or cord blood, 12, 48week) >Bone mineral content and bone mineral density will be determined as the markers for ossification using dual-energy X-ray absorptiometry, and the bone mass in the process of ossification in HPP patients will be quantified. Moreover, Lean Body Mass will be determined by DXA as a quantitative marker for muscle mass (48, 96week)

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	1 days-old <=
Age-upper limit	183 days-old >=
Gender	Male and Female
Key inclusion criteria	1.Patients who have not been treated with asfotase alfa 2.Patients aged younger than 6 months at the time of enrollment 3.Patients diagnosed as hypophosphatasia 4.Patients who fall under any of the following items (1) to (6), and who are judged by the physicians to be likely to have HPP (1)The serum total ALP level is lower than the standard value for the age and gender. (2)Fetal ultrasound findings 1)Markedly short extremities (femur length (FL) of -4SD or less in the second and third pregnancy trimesters) 2)Fraying of metaphysis 3)Craniotabes (deformation of the cranial bone by mild compression by a probe) 4)Thoracic hypoplasia (3)Fetal CT findings 1)Marked ossification insufficiency in the whole body 2)Shortening of long bones 3)Metaphyseal cupping 4)Thoracic hypoplasia (4)Following radiographic findings unique to HPP 1)Metaphyseal flaring and fraying 2)Systemic osteopenia 3)Enlargement of growth cartilage area 4)Findings of the metaphyseal radiolucent tongue-like protrusion or sclerosis (5)Two or more items in the following HPP-related findings are satisfied. 1)Past or present history of the following conditions 1.Prenatal or postnatal non-traumatic fracture 2.Delay in fracture healing 2)Past history of nephrocalcinosis and hypercalcemia 3)Craniosynostosis 4)Respiratory dysfunction or rickets-like thoracic deformation 5)Vitamin B6-dependent convulsive seizures 6)Failure to thrive (6)Mutation in the ALPL gene encoding tissue-nonspecific alkaline phosphatase has been identified. 5.Patients for whom informed consent can be obtained in writing from their legally authorized representatives
Key exclusion criteria	1.Patients diagnosed as having rickets from causes other than HPP, such as vitamin D deficient rickets 2.Patients diagnosed as skeletal dysplasia other than HPP, such as osteogenesis imperfecta and campomelic dysplasia 3.Patients with serum calcium concentrations or phosphorus concentrations lower than the lower limit of the institutional standard values of the study sites 4.The serum total ALP level is not lower than the lower limit of the standard values for corresponding age and gender. 5.Patients participating in clinical trials using the drugs, medical devices or treatment methods that are not approved in Japan or at study sites 6.Patients having clinically significant diseases, who is judged by investigators not to be able to participate in this study
Target sample size	20

Research contact person
Name of lead principal investigator	1st name Takuo Middle name Last name Kubota
Organization	Osaka University
Division name	Dept. of Pediatrics, Graduate School of Medicine
Zip code	565-0871
Address	2-2 Yamadaoka, Suita, Osaka, Japan
TEL	06-6879-3932
Email	tkubota@ped.med.osaka-u.ac.jp

Public contact
Name of contact person	1st name Takuo Middle name Last name Kubota
Organization	Osaka University
Division name	Dept. of Pediatrics, Graduate School of Medicine
Zip code	565-0871
Address	2-2 Yamadaoka, Suita, Osaka, Japan
TEL	06-6879-3932
Homepage URL
Email	tkubota@ped.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University
Institute
Department

Funding Source
Organization	Alexion Pharma GK
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Osaka University
Address	2-2 Yamadaoka, Suita, Osaka, Japan
Tel	06-6210-8296
Email	rinri@hp-crc.med.osaka-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

大阪大学医学部附属病院（大阪府）、岡山大学病院（岡山県）、島根大学医学部附属病院（島根県）、新潟大学医歯学総合病院（新潟県）、地域医療機能推進機構（JCHO）大阪病院（大阪府）、名古屋大学医学部附属病院（愛知県）、東北大学病院（宮城県）、大阪母子医療センター（大阪府）、宮城県立こども病院（宮城県）、埼玉県立小児医療センター（埼玉県）、安城更生病院（愛知県）、金沢大学附属病院（石川県）、奈良県立医科大学附属病院（奈良県）、兵庫県立こども病院（兵庫県）、千葉県こども病院（千葉県）、函館五稜郭病院（北海道）、久留米大学病院（福岡県）、順天堂大学医学部附属静岡病院（静岡県）、鳥取大学医学部附属病院（鳥取県）、大阪発達総合医療センター（大阪府）、あいち小児保健医療総合センター（愛知県）、北海道医療大学（北海道）、埼玉医科大学病院（埼玉県）、長野県立こども病院（長野県）、大分大学医学部附属病院（大分県）、筑波大学附属病院（茨城県）、豊橋市民病院（愛知県），名古屋第一日赤医療センター（愛知県）

Other administrative information
Date of disclosure of the study information	2018 Year 09 Month 18 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2018 Year 05 Month 08 Day
Date of IRB	2018 Year 05 Month 08 Day
Anticipated trial start date	2018 Year 05 Month 08 Day
Last follow-up date	2022 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	Observational study of perinatal and infantile hypophosphatasia

Management information
Registered date	2018 Year 09 Month 14 Day
Last modified on	2022 Year 03 Month 18 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037950