UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000030575 |
|---|---|
| Receipt number | R000034909 |
| Scientific Title | Comparative study of the inhibitory effect on bone erosion progression with Denosumab treatment and conventional treatment in rheumatoid arthritis patients. An open label randomized controlled trial by HR-pQCT. |
| Date of disclosure of the study information | 2017/12/26 |
| Last modified on | 2022/12/20 18:24:09 |
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Basic information
Public title
Comparative study of the inhibitory effect on bone erosion progression with Denosumab treatment and conventional treatment in rheumatoid arthritis patients.
An open label randomized controlled trial by HR-pQCT.
Acronym
Comparative study of the inhibitory effect on bone erosion progression with Denosumab treatment and conventional treatment in rheumatoid arthritis patients.
An open label randomized controlled trial by HR-pQCT.
Scientific Title
Comparative study of the inhibitory effect on bone erosion progression with Denosumab treatment and conventional treatment in rheumatoid arthritis patients.
An open label randomized controlled trial by HR-pQCT.
Scientific Title:Acronym
Comparative study of the inhibitory effect on bone erosion progression with Denosumab treatment and conventional treatment in rheumatoid arthritis patients.
An open label randomized controlled trial by HR-pQCT.
Region
| Japan |
Condition
Condition
Rheumatoid arthritis
Classification by specialty
| Clinical immunology | Orthopedics |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
To compare inhibitory effect on bone erosion progression in Denosumab treatment and conventional treatment in rheumatoid arthritis patients under treatment with csDMARDs.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Pragmatic
Developmental phase
Not applicable
Assessment
Primary outcomes
Depth change from baseline of bone erosion by HR-pQCT measurement 6 months after starting administration.
Measurement part: second, third metacarpal bone
Key secondary outcomes
Depth change from baseline of bone erosion by HR-pQCT measurement 12 months after starting administration.
Measurement part: second, third metacarpal bone
Depth change from baseline of bone erosion by HR-pQCT measurement.
Measurement part: wrist joint
Width and Volume change from baseline of bone erosion by HR-pQCT measurement.
Measurement part: second, third metacarpal bone and wrist joint
Base
Study type
Interventional
Study design
Basic design
Parallel
Randomization
Randomized
Randomization unit
Individual
Blinding
Open -no one is blinded
Control
Active
Stratification
NO
Dynamic allocation
YES
Institution consideration
Institution is not considered as adjustment factor.
Blocking
NO
Concealment
Central registration
Intervention
No. of arms
2
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
Patients of the group that starts treatment of Denosumab will be treated with Denosumab at the time of visit on Month 0 and Month 6.
Interventions/Control_2
Patients of the group that continues conventional treatment will be not treated with Denosumab as a rule.
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
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
1) Patients who can be visited hospital diagnosed as rheumatoid arthritis by Rheumatoid arthritis classification criteria of ACR (revised in 1987) or ACR / EULAR (2010)
2) Patients with low or moderate disease activity
3) Patients under treatment with csDMARDs.
4) Patients with progressive bone erosion in image examination (either X-ray, MRI or ultrasound)
5) Patients who are 20 years older at the time of obtaining informed consent and can consent to the document to participate by my own will
6) Male and Female
7) Outpatient only
Key exclusion criteria
1) Patients complicated of osteoporosis who have not been treated for osteoporosis
2) Patients under treatment with intravenous bisphosphonate formulation and parathyroid hormone formulation
3) Patients under treatment with Denosumab
4) Patients under treatment with Biological disease-modifying anti-rheumatic drug and JAK inhibitor
5) Patients taking adrenal cortex hormone drug in excess of 10 mg / day in terms of prednisolone
6) Patients with a history of hypersensitivity to the components of Desnomab
7) Patients with hypocalcemia
8) Patients who are or may be pregnant
9) Patients currently participating in trials or studies of other medicines or medical devices
10) Patients who are breastfeeding or who want pregnancy during the study period
11) Patients who jugged unsuitable for this study by the investigator
Target sample size
44
Research contact person
Name of lead principal investigator
| 1st name | Atsushi |
| Middle name | |
| Last name | Kawakami |
Organization
Nagasaki University Hospital
Division name
Department of Immunology and Rheumatology
Zip code
852-8501
Address
1-7-1 Sakamoto Nagasaki, Nagasaki
TEL
095-819-7200
atsushik@nagasaki-u.ac.jp
Public contact
Name of contact person
| 1st name | Fumiyuki |
| Middle name | |
| Last name | Iida |
Organization
EP-CRSU Co., Ltd
Division name
Clinical Research Management Center, CRM Department1
Zip code
162-0814
Address
Acropolis Tokyo Bldg. 3F 6-29 Shinogawamachi, Shinjuku-ku, Tokyo
TEL
03-6759-9900
Homepage URL
prl-ds-17012@eps.co.jp
Sponsor or person
Institute
Daiichi Sankyo Company, Limited
Institute
Department
Personal name
Funding Source
Organization
Daiichi Sankyo Company, Limited
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
Nagasaki University Hospital Clinical Research Ethics Committee
Address
1-7-1 Sakamoto, Nagasaki-shi, Nagasaki-ken
Tel
095-819-7229
gaibushikin@ml.nagasaki-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
長崎大学病院（長崎県）、日本赤十字社長崎原爆病院（長崎県）、社会医療法人春回会長崎北病院（長崎県）
Other administrative information
Date of disclosure of the study information
| 2017 | Year | 12 | Month | 26 | Day |
Related information
URL releasing protocol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691552/pdf/13063_2019_Article_3589.pdf
Publication of results
Published
Result
URL related to results and publications
https://link.springer.com/content/pdf/10.1186/s13075-022-02957-w.pdf
Number of participants that the trial has enrolled
46
Results
The aim of this exploratory study was to compare the effects of denosumab in combination with csDMARDs and csDMARDs alone on ER inhibition by HRpQCT in patients receiving csDMARDs for the treatment of RA. The results of the study suggested that the additional administration of denosumab may be effective in inhibiting the progression of bone erosion and improving bone erosion. Adverse drug reactions of Denosumab treatment were observed in 26.1%, and hypocalcemia was the most common in 17.4%, it was feasible.
Results date posted
| 2022 | Year | 12 | Month | 20 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2022 | Year | 12 | Month | 07 | Day |
Baseline Characteristics
In the denosumab treatment group (21 patients) and the conventional treatment group (22 patients), the mean+-SD of age (years) was 65.6+-8.5 and 65.0+-9.2, the percentage of females was 85.7% and 90.9%, the mean+-SD of disease duration (months) was 162.3+-151.3 and 150.5+-129.0, the percentage of patients with anti-CCP antibody was 76.2% and 77.3%, the mean+-SD of anti-CCP antibody (U/mL) was 76.8+-115.2 and 85.4+-108.2, the percentage of patients with rheumatoid factor was 81.0% and 81.8%, the percentage of patients with bone erosion (HR-pQCT 2nd and 3rd metacarpal bones) was 38.1% and 59.1%.
Participant flow
Forty-six patients were enrolled in this study, randomized to Denosumab treatment group (23 patients) and Conventional treatment group (23 patients). In the Denosumab treatment group, 21 patients were included in FAS (Two patients were excluded from FAS because the test was not performed), of which 20 patients were completed and one patient was discontinued (Because there was an offer to discontinue). In the conventional treatment group, 22 patients were included in FAS (One patient was excluded from FAS because the test was not performed), of which 21 patients were completed and one patient was discontinued (Due to adverse event).
Adverse events
In the safety analysis set, Adverse events that occurred between month 0 and month 12 were 52.2% (12/23) in the Denosumab treatment group (All patients received Denosumab at least one dose) and 56.5% (13/23) in the conventional treatment group. Serious adverse events were 4.3% (1/23, osteoarthritis) in the Denosumab treatment group and 8.7% (2/23, malignant neoplasm of the lung and subdural hematoma) in the conventional treatment continuation group.
Outcome measures
[Primary endpoint]
The estimate mean (95%CI) change of ER-depth at month 6 from baseline was -0.57 (-1.52, 0.39) in the denosumab-treated group vs -0.22 (-0.97, 0.53) in the conventional treatment continuation group, respectively. The estimated difference in the adjusted mean change in HR-pQCT bone erosion (depth [mm]) from baseline to 6 months after the start of treatment in the denosumab-treated group and the conventional treatment continuation group was -0.35. (95% CI: -1.00, 0.31, P = 0.272).
[Secondary evaluation items]
The estimate mean (95%CI) change at month 12 from baseline and the estimated difference in the adjusted mean change from baseline to 12 months after the start of treatment in the denosumab-treated group and the conventional treatment continuation group of the depth (mm) , width (mm) and volume(mm3) of HR-pQCT bone erosion in 'the 2nd and 3rd metacarpal bones' and 'wrist joint' are shown below.
The 2nd and 3rd metacarpal bones:
Depth(mm):-0.56 (-1.41, 0.29),-0.20 (-0.90, 0.49),-0.35(P = 0.225)
Width(mm):-0.27 [-1.10, 0.56],-0.03 [-0.70, 0.64],-0.24(P = 0.436)
Volume(mm3):-6.25 [-23.94, 11.44],-3.18 [-17.56, 11.20],-3.07(P = 0.598)
The wrist joint:
Depth(mm):0.02(-0.18, 0.22),-0.07(-0.29, 0.15),0.09(P = 0.447)
Width(mm):0.13(-0.09, 0.34),0.32(0.11, 0.52),-0.19(P = 0.131)
Volume(mm3):-0.44(-1.04, 0.16),-0.40(-1.01, 0.22),-0.05(P = 0.890)
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2017 | Year | 12 | Month | 04 | Day |
Date of IRB
| 2018 | Year | 01 | Month | 16 | Day |
Anticipated trial start date
| 2018 | Year | 03 | Month | 31 | Day |
Last follow-up date
| 2021 | Year | 04 | Month | 28 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2017 | Year | 12 | Month | 26 | Day |
Last modified on
| 2022 | Year | 12 | Month | 20 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034909
