UMIN-CTR Clinical Trial

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

osteoporosis

Classification by specialty

Orthopedics

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Amgen K.K.
Medical Affairs Japan

Institute

Department

Personal name

Organization

Amgen K.K.
Medical Affairs Japan

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2020

Year

11

Month

26

Day

URL releasing protocol

Publication of results

Published

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

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 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

Registered date

2020

Year

11

Month

25

Day

Last modified on

2022

Year

03

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048505