UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A multicenter, investigator-initiated phase II clinical trial involving administration of a cross-linked gelatin hydrogel containing recombinant human basic fibroblast growth factor (rh-bFGF) to prevent the collapse of the femoral head
Title of the study (Brief title)	A clinical trial for idiopathic osteonecrosis of femoral head using trafermin (genetical recombination) gelatin hydrogel to evaluate the effectiveness and the safety (TRION)
Region	Japan

Condition
Condition	Osteonecrosis of the femoral head
Classification by specialty	Orthopedics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To assess the efficacy and safety of administering, via a minimally invasive procedure, a cross-linked gelatin hydrogel (denoted here simply as a "gelatin hydrogel") containing genetical recombinant trafermin (rh-bFGF) in the femoral head in patients with idiopathic osteonecrosis of the femoral head. To observe the natural history of osteonecrosis of the femoral head in patients and to use these patients as a control group to compare the efficacy of the gelatin hydrogel containing trafermin.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase II

Assessment
Primary outcomes	The rate of collapse of the femoral head 24 months after administration of the investigational agent
Key secondary outcomes	1.Changes in collapse of the femoral head over time 2.The stage of osteonecrosis of the femoral head over time 3.The type of osteonecrosis of the femoral head over time 4.Assessment of bone regeneration 5.Changes in the Harris Hip Score over time 6.Changes in the UCLA Activity Score over time 7.Incidence of AEs and adverse reactions

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Gelatin hydrogel containing 800 ug of trafermin (genetical recombination)
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	15 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Osteonecrosis of the femoral head meets the diagnostic criteria for that condition and is Stage 1 or Stage 2. 2) Osteonecrosis of the femoral head is Type C1 or C2 depending on the location of necrosis. 3) A gelatin hydrogel can be administered to the necrotic region in the affected femur (guide pins are able to reach the necrotic portion of the femoral head). 4) Patients are ages 15 to 75 when they consent to participate in this trial. 5) The patient is able to provide consent to participate in this trial in writing. If the patient is a minor, the consent of the patient and his/her representative (guardian) is required.
Key exclusion criteria	1) Preoperatively, a plain CT scan of the hip reveals cracks in subchondral bone in the femoral head or disruption of the continuity of the femoral head and neck. 2) Patients with a tumor or tumor-like condition, epiphyseal dysplasia, trauma (e.g. femoral neck fracture or traumatic dislocation of the hip), or slipped capital femoral epiphysis, patients receiving pelvic radiation, patients with decompression sickness and osteonecrosis of the femoral head, and patients with Perthes disease. 3) Patients who were diagnosed with osteonecrosis of the femoral head and who previously underwent this surgery. 4) Patients with a BMI of 30 or greater. 5) Patients with any of the following conditions: *Conditions that could pose major obstacles to the conduct of this trial (poorly controlled diabetes, hypertension, severe heart disease, respiratory disease, renal failure, hepatic failure, etc.) *Patients with a malignancy who have been disease-free for less than 5 years (However, carcinoma in situ and intramucosal carcinoma are not included in active malignancies) *Patients with a psychiatric disorder or psychiatric symptoms that would preclude participation in this trial *Patients with an active infection that would pose a problem clinically. 6) Patients being treated for diabetic retinopathy. (pre-proliferative diabetic retinopathy or proliferative diabetic retinopathy). 7) Patients with a previous history of any of the following: *A gelatin allergy *Patients with a drug allergy or other condition that would pose a problem during this trial. 8) Patients requiring continuous systemic administration of steroids (a dose exceeding an equivalent prednisolone dose of 15 mg/day). 9) Women who are or may be pregnant. Women who are nursing. Men or women who do not consent to use of contraception during this trial. 10) Other individuals whom an investigator or sub-investigator deems inappropriate for participation in this trial.
Target sample size	64

Research contact person
Name of lead principal investigator	Haruhiko Akiyama
Organization	Gifu University Hospital
Division name	Department of Orthopaedic Surgery
Address	1-1 Yanagido, Gifu City 501-1194, Japan
TEL	058-230-6000
Email	trion_office@ml.kuhp.kyoto-u.ac.jp

Public contact
Name of contact person	Yutaka Kuroda
Organization	Kyoto University Hospital
Division name	Department of Orthopaedic Surgery
Address	54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 JAPAN
TEL	075-751-3111
Homepage URL	http://hosp.gifu-u.ac.jp/medical/seikei/tiken.html
Email	trion_office@ml.kuhp.kyoto-u.ac.jp

Sponsor
Institute	Haruhiko Akiyama, Gifu University Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development (AMED)
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

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

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	岐阜大学医学部附属病院(Gifu University Hospital)、京都大学医学部附属病院(Kyoto University Hospital)、東京大学医学部附属病院(The University of Tokyo　Hospital)、大阪大学医学部附属病院（Osaka University Hospital）

Other administrative information
Date of disclosure of the study information	2015 Year 12 Month 25 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 10 Month 20 Day
Anticipated trial start date	2016 Year 01 Month 27 Day
Last follow-up date	2018 Year 12 Month 31 Day
Date of closure to data entry	2019 Year 04 Month 30 Day
Date trial data considered complete	2019 Year 06 Month 30 Day
Date analysis concluded	2019 Year 10 Month 30 Day

Related information
URL releasing protocol	http://www.kuhp.kyoto-u.ac.jp/~seikeigeka/ekigaku/TRION.pdf
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 12 Month 25 Day
Last modified on	2019 Year 01 Month 07 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023495