臨床研究等提出・公開システム

A Confirmatory Study of AMG 162 (Denosumab) in Patients with Rheumatoid Arthritis on DMARDs treatment (Phase III)

AMG 162 Phase III study (DESIRABLE study)

667

Of 654 FAS subjects, 74.8% were women. The mean age was 57.4 years (SD, 12.04) and the mean weight was 56.70 kg (SD, 10.855 kg). The mean duration of rheumatoid arthritis was 2.16 years (SD, 1.308 years) and 61.9% of subjects had positive RF results at baseline. Overall, 20.2% of subjects had osteoporosis. At baseline, 32.1% of subjects were receiving glucocorticoid and 84.9% MTX. The mean weekly MTX dose was 9.65 mg (SD, 3.126). As determined using the modified Sharp methods, the mean TSS was 14.745 (SD, 20.9136), the mean ES was 7.081 (SD, 10.0353), and the mean JSN score was 7.664 (SD, 12.2681). No relevant imbalances among the treatment groups were noted in the demographic and other characteristics.

A total of 679 subjects were randomized (placebo group: 226 subjects, denosumab 60 mg Q6M group: 228 subjects, Q3M group: 225 subjects), and 667 subjects of them received the study drug (placebo group: 223 subjects, Q6M group: 222 subjects, Q3M group: 222 subjects). A total of 60 subjects discontinued the study, and 607 subjects completed the study (placebo group: 208 subjects, Q6M group: 199 subjects, Q3M group: 200 subjects).

The overall incidence of adverse events was 83.0% (186/224) in the placebo group, 85.1% (188/221) in the Q6M group, and 83.3% (185/222) in the Q3M group (hereafter, results are presented in the same order). The overall incidence of adverse events related to the investigational product was 17.0% (38/224), 17.6% (39/221), and 16.7% (37/222), respectively. A subject of the Q3M group experienced a fatal adverse event.

The mean change (SD) from baseline in TSS at Month 12 was 1.488 (3.7558) for the placebo group, 0.989 (3.7677) for the Q6M group, and 0.720 (2.3224) for the Q3M group. The change was significantly smaller in each AMG 162 group than in the placebo group (Q6M, P = 0.0235; Q3M, P = 0.0055).

The change at Month 6 was significantly smaller in each AMG 162 group than in the placebo group (Q6M, P = 0.0360; Q3M, P = 0.0028). The change from baseline in ES at Month 12 was significantly smaller in each AMG 162 group than in the placebo group (Q6M, P = 0.0104; Q3M, P = 0.0001). At Month 6, the change in the Q3M group was significantly smaller than in the placebo group (P = 0.0002). No effect of AMG 162 on the JSN score was observed; none of the differences in the changes from baseline in JSN score at Months 6 and 12 between each AMG 162 group and the placebo group were significant, except at Month 6 for the Q6M group (P = 0.0448). Proportions of subjects with change <=0.5 in TSS were 70.2% in the placebo group, 78.8% in the Q6M group, and 80.4% in the Q3M group at Month 6, and 64.2%, 75.6%, and 78.1%, respectively, at Month 12. The proportions at Months 6 and 12 were significantly higher in both AMG 162 groups than in the placebo group (P = 0.0014-0.0372). Increases in BMD of lumbar spine (L1 to L4) from baseline, with no imputation, were significantly greater at Month 12 in both AMG 162 groups than in the placebo group (both groups, P < 0.0001).

When AMG 162 60 mg was subcutaneously administrated every 6 months or 3 months for 12 months to rheumatoid arthritis patients on DMARDs, both regimens demonstrated significant inhibitory effects, compared with placebo, on the progression of joint destruction, with the change in TSS being smaller for Q3M than for Q6M. Both AMG 162 regimens demonstrated a safety profile similar to that of placebo, indicating that AMG 162 Q6M and Q3M were well tolerated.

April. 29, 2019

https://ard.bmj.com/content/78/7/899.full

Yes

Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Oct. 29, 2013

Interventional

Randomized, double-blind, placebo-controlled

treatment purpose

3

Diagnosed with rheumatoid arthritis according to the American College of Rheumatology (ACR) criteria for rheumatoid arthritis classification (1987 revision) or the 2010 ACR-EULAR (The European League Against Rheumatism) classification criteria for rheumatoid arthritis

Functional class IV according by the ACR revised classification (1991)

Both

rheumatoid arthritis

investigational material(s)
Generic name etc : AMG 162
INN of investigational material : Denosumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : Administer 60 mg every 6 months or every 3 months as a subcutaneous injection

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Administer placebo as a subcutaneous injection

safety
efficacy
confirmatory
total Sharp score(TSS)
modified Sharp method

efficacy
1: Erosion Score, Joint Space Narrowing score
2: BMD

1: modified Sharp method
2: DXA method

Oct. 28, 2013