UMIN-CTR Clinical Trial

Basic information
Public title	A Multi-Center Retrospective Study to Describe Clinical Characteristics and Outcomes of Early EVENITY Users, Transitioning to Antiresorptive Agents in Japan
Acronym	A Multi-Center Retrospective Study to Describe Clinical Characteristics and Outcomes of Early EVENITY Users, Transitioning to Antiresorptive Agents in Japan
Scientific Title	A Multi-Center Retrospective Study to Describe Clinical Characteristics and Outcomes of Early EVENITY Users, Transitioning to Antiresorptive Agents in Japan
Scientific Title:Acronym	A Multi-Center Retrospective Study to Describe Clinical Characteristics and Outcomes of Early EVENITY Users, Transitioning to Antiresorptive Agents in Japan
Region	Japan

Condition
Condition	osteoporosis
Classification by specialty	Orthopedics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	<Primary> To describe the clinical characteristics of Japanese osteoporosis patients who completed 12 months of EVENITY therapy and transitioned to antiresorptive agents. <Secondary> To describe changes in BMD and BTMs from baseline to 12 months (completion of EVENITY therapy) and 18 months of treatment (at least 6 months of first sequential therapy post EVENITY therapy).
Basic objectives2	Others
Basic objectives -Others	Clinical Characteristics
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	- Baseline demographics (age, sex, years since menopause, weight, height) at the initiation of EVENITY - Recent BMD T-score - Prevalent Fxs (including timing of most recent) - Family history of hip Fxs - Rheumatoid Arthritis (RA) prevalence - Co-administered medications (eg, active vitamin D3) - Most recent previous OP medications (active vitamin D3, selective estrogen receptor modulators [SERMs], bisphosphonates [BISs], denosumab, teriparatide [TPTD]) - History of cardiovascular disease, and other comorbidities - Healthcare utilization preceding initiation of EVENITY - Substance use (smoking status and alcohol consumption at EVENITY initiation) - 10-year probability of major osteoporotic and hip FXs based on WHO risk factor criteria (FRAX) calculated with actual femoral neck BMD (in g/cm2) or T-score
Key secondary outcomes	- Absolute value and percent change from baseline at each available time points for BTMs (Type I procollagen-N-propeptide [P1NP], bone specific alkaline phosphatase [BAP], Type I collagen cross-linked C-telopeptide [CTX], tartrate-resistant acid phosphatase 5b [TRACP-5b], Type I collagen cross-linked N-telopeptide [NTX]) and BMD (lumbar spine [LS], total hip [TH], femoral neck [FN]) at 12 months (completion of EVENITY therapy) from baseline - Absolute value and percent change in BMD and BTMs at 18 months (at least 6 months of first sequential therapy post EVENITY therapy) from baseline - Adherence/compliance during EVENITY therapy - Types of first sequential therapy following EVENITY therapy and the reasons for the choice of the sequential therapy

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	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Patients diagnosed with OP at high risk of fracture, defined by the Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society as below (at least one of the following must be met): - Any of LS, TH, or FN BMD below -2.5 standard deviation (SD) and history of at least one fragility fracture - LS BMD less than -3.3 SD - Presence of 2 or more prevalent vertebral Fxs - Any prevalent vertebral Fxs with semi-quantitative (SQ) grade 3 - Other risk factors (cf. prevalent hip fracture) 2. Patients starting treatment with EVENITY after 4th March 2019 and completing 12 months of treatment and having first sequential therapy data for 6 months or longer.
Key exclusion criteria	Conditions specified as contraindication in Japanese package insert: - Patients with a history of hypersensitivity to any of the ingredients of EVENITY - Patients with hypocalcemia
Target sample size	1000

Research contact person
Name of lead principal investigator	1st name Etsuro Middle name Last name Hamaya
Organization	Amgen K.K.
Division name	Medical Affairs
Zip code	107-6239
Address	Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo Japan
TEL	03-5293-9658
Email	ehamaya@amgen.com

Public contact
Name of contact person	1st name Takashi Middle name Last name Takahashi
Organization	IQVIA Services Japan K.K.
Division name	Real-World Evidence Services
Zip code	108-0074
Address	Keikyu Dai-ichi Bldg 4-10-18, Takanawa, Minatoku, Tokyo, Japan
TEL	03-6859-9500
Homepage URL
Email	takashi.takahashi@iqvia.com

Sponsor
Institute	Amgen K.K. Medical Affairs Japan
Institute
Department

Funding Source
Organization	Amgen K.K. Medical Affairs Japan
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	Medical Corporation TOUKEIKAI Kitamachi Clinic ERB
Address	1-1-3 Kitamachi, Musashino-city, Tokyo
Tel	03-6779-8166
Email	chi-pr-ec-kitamachi@cmicgroup.com

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

Other administrative information
Date of disclosure of the study information	2020 Year 11 Month 26 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications
Number of participants that the trial has enrolled	1027
Results	There was a total of 1027 patients in this study of which >=90% were female. The mean age at the initiation of EVENITY for all patients was 77.0 years. A percentage of 54.9% of patients had previous OP medications within 6 months before EVENITY initiation. At 12 and 18 months of treatment, the mean percent change in BMD from baseline was 13.4% and 13.8% for the LS, 4.0% and 4.8% for TH, and 3.6% and 4.5% for FN in the FAS.
Results date posted	2022 Year 03 Month 04 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2021 Year 10 Month 01 Day
Baseline Characteristics	There was a total of 1,027 patients in this study of which >=90% were female. The mean age at the initiation of EVENITY for all patients was 77.0 years. A percentage of 54.9% of patients had previous OP medications within 6 months before EVENITY initiation. The top three previous OP medication were BISs (45.2%), TPTDs (24.9%), and denosumab (16.9%). The most frequently used BIS and TPTDs were minodronic acid hydrate (35.4%) and teriparatide (genetical recombination) (69.3%).
Participant flow	Of the 1,040 enrolled patients, 1,027 patients were included in the FAS and 13 patients were excluded.
Adverse events	Safety data was not collected in this study.
Outcome measures	There was a total of 1,027 patients in this study of which >=90% were female. The mean age at the initiation of EVENITY for all patients was 77.0 years. A percentage of 54.9% of patients had previous OP medications within 6 months before EVENITY initiation. The top three previous OP medication were BISs (45.2%), TPTDs (24.9%), and denosumab (16.9%). The most frequently used BIS and TPTDs were minodronic acid hydrate (35.4%) and teriparatide (genetical recombination) (69.3%). After 12 months of EVENITY therapy, the top three first sequential therapies used were denosumab (genetical recombination) (56.0%), BISs (25.9%) and active vitamin D3 (9.9%). At 12 and 18 months of treatment, the mean percent change in BMD from baseline was 13.4% and 13.8% for the LS, 4.0% and 4.8% for TH, and 3.6% and 4.5% for FN in the FAS. At 12 and 18 months, the median (Q1 - Q3) values of P1NP at baseline (n=555), at 12 months (n=545) and at 18 months (n=396) were 53.0 (27.7 - 81.5), 45.2 (31.5 - 73.0), and 18.9 (13.5 - 31.0), respectively. At 12 months and 18 months the median (Q1 - Q3) values for BSAP (micro g/L) at baseline (n=115), at 12 months (n=123) and at 18 months (n=93) were 11.7 (8.4 - 16.3), 13.7 (11.2 - 17.6), and 8.5 (7.0 - 11.7), respectively. The median (Q1 - Q3) values for TRACP-5b at baseline (n=482), at 12 months (n=441) and at 18 months (n=317) were 412.0 (272.0 - 575.0), 274.00 (206.0 - 399.0), and 229.0 (168.0 - 326.0), respectively. At 12 months and at 18 months, the median (Q1 - Q3) values for NTX in serum at baseline (n=90), at 12 months (n=108), and at 18 months (n=76) were 14.0 (11.9 -16.4), 13.4 (11.8 - 15.4), and 12.9 (11.8 - 15.2), respectively. The median (Q1 - Q3) values for NTX in urine at baseline (n=12), at 12 months (n=7), and at 18 months (n=37) was 59.1 (43.8 - 90.8), 57.3 (39.3 - 82.1), and 27.6 (17.9 - 40.6), respectively. The most common reason for choice of sequential therapy was the requirement of more BMD gain.
Plan to share IPD	NA
IPD sharing Plan description	NA

Progress
Recruitment status	Completed
Date of protocol fixation	2020 Year 07 Month 30 Day
Date of IRB	2020 Year 10 Month 21 Day
Anticipated trial start date	2020 Year 11 Month 27 Day
Last follow-up date	2021 Year 04 Month 13 Day
Date of closure to data entry	2021 Year 06 Month 23 Day
Date trial data considered complete	2021 Year 06 Month 30 Day
Date analysis concluded	2021 Year 09 Month 07 Day

Other

Other related information

Disclosure of clinical study [Purpose and method of data collection] The study objective is to gain a deep understanding of the clinical characteristics and the treatment outcomes of the osteoporosis patients at high risk of fracture with EVENITY after 4 Mar 2019 for 12 months and sequential therapy for 6 months or longer. In the study, the data from medical records will be collected without any clinical samples (i.e., blood). The study results may provide useful and important information for the osteoporosis treatment in future and contribute to the patients and to the society as a whole. [Information to be used or provided] This observational study is a multi-center study in Japan to collect the data of a total of about 1,000 patients at 20 institutions. During the study period from the Ethics Committee approval date to 30Jun2021, the following data on the medical records in the normal medical care will be collected. The data will be anonymized by the doctors or the study staff, and entered electronically into the secured systems on the Internet with the restricted access. - Demographic information: age, gender, height, weight, etc. - Medical history / complications - Concomitant drug - Data on current treatment and treatment history for osteoporosis - Clinical test results related to osteoporosis - Daily smoking / drinking status [Scope of users] This study is sponsored by Amgen K.K. The collected data and the analysis results will be provided to Amgen K. K. and shared among the Amgen affiliates in Japan and overseas. The study staff in the institutions will use the information to conduct the study. Also, the information may be shared with other collaborative institutes. The collection and analysis will be conducted by IQVIA Services Japan Co., Ltd., designated by Amgen K.K. [Name of the person in charge of the information management] Amgen K.K. Medical Affairs Etsuro Hamaya

Management information
Registered date	2020 Year 11 Month 25 Day
Last modified on	2022 Year 03 Month 11 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048505