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A Phase II/III Study of TS-152 in Patients with Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to Methotrexate (MTX) Therapy

A Phase II/III Study of TS-152 in Patients with Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to Methotrexate (MTX) Therapy

381

Of 381 FAS subjects, all subjects were Japanese, and 74.8% were female. The mean age was 55.0 years (SD, 11.2) , the mean weight was 58.72 kg (SD, 12.49) , the mean duration of rheumatoid arthritis was 7.4 years (SD, 7.1) and the mean weekly MTX dose was 10.1 mg (SD, 2.8). No relevant imbalances among the treatment groups were noted in the demographic and other characteristics.

A total of 395 subjects were randomized and 381 subjects of them received the study drug (placebo group: 75 subjects, 30 mg group: 152 subjects, 80 mg group: 154 subjects).Of 381 subjects who received the study drug, 352 subjects completed treatment period A(double blind)(placebo group: 67 subjects, 30 mg group: 141 subjects, 80 mg group: 144 subjects). Early Escape criteria applied to 21 subjects in the placebo group, 9 subjects in the 30 mg group, and 11 subjects in the 80 mg group. Of the 67 subjects in the placebo group who completed treatment period A, 44 subjects received 30 mg (P/30 mg group) and 23 subjects received 80 mg (P/80 mg group) in treatment period B. In addition, there were 9 subjects who received 80 mg in treatment period B after receiving 30 mg in treatment period A (30/80 mg group). 335 subjects completed treatment period B(P/30 mg group: 42 subjects, P/80 mg group: 22 subjects, 30 mg group: 125 subjects, 30/80 group: 7 subjects, 80 mg group: 139 subjects).

The incidence of adverse event (AE) up to 24 weeks was 62.7% in the placebo group (47/75), 76.3% in the 30 mg group (116/152), and 72.1% in the 80 mg group (111/154). The incidence of adverse drug reaction (ADR) up to 24 weeks was 18.7% (14/75), 27.6% (42/152), and 25.3% (39/154) respectively. The incidence of AE up to 52 weeks was 72.7% in the P/30 mg group (32/44), 82.6% in the P/80 mg group (19/23), 90.2% in the 30 mg group (129/143), 88.9% in the 30/80 mg group (8/9), and 89.0% in the 80 mg group (137/154). The incidence of ADR up to 52 weeks was 43.2% (19/44), 39.1% (9/23), 42.7% (61/143), 33.3% (3/9), and 40.3% (62/154) respectively. AE that resulted in death was observed up to 24 weeks in one subject in the 80 mg group, in whom disseminated tuberculosis had developed. It was deemed to have a causal relationship with TS-152. The incidences of AE/ADR in the 30 mg and 80 mg ozoralizumab groups were comparable.No adverse device reactions were reported.

ACR20 response rate at week 16 (complemented using LOCF) was 37.3% in the placebo group (28/75), 79.6% in the 30 mg group (121/152), and 75.3% in the 80 mg group (116/154). The intergroup difference from the placebo group was 42.1 [95 confidence interval (CI): 28.7-53.7, p < 0.001, Cochran-Mantel-Haenszel test] in the 30 mg group, and 37.9 (CI: 24.4-49.7, p < 0.001, Cochran-Mantel-Haenszel test) in the 80 mg group, indicating a significantly higher improvement rate in the TS-152 groups compared with that in the placebo group. ACR20 response rate in the TS-152 groups was comparable irrespective of the dose. Change from baseline (least-squares mean) in the mTSS score at week 24 (complemented using the linear extrapolation method) was 0.8 in the placebo group, 0.6 in the 30 mg group, and 0.4 in the 80 mg group. The intergroup difference from the placebo group was -0.3 (CI: -0.8-0.3) in the 30 mg group, and -0.5 (CI: -1.0-0.1) in the 80 mg group. Using analysis of covariance with baseline value and history of TNF inhibitor usages, no statistically significant inhibition of progression was observed in both TS-152 groups compared with the placebo group.

With regard to secondary endpoints [ACR50, ACR70, DAS28-CRP, DAS28-ESR, ACR-N, TJC(68), SJC(66), Pt-GA, Ph-GA, Pt-PA, duration of morning stiffness, EULAR response rate (CRP), EULAR response rate (ESR), CDAI, SDAI, Boolean remission rate, HAQ-DI, EQ-5D-5L] at week 16 (complemented using LOCF), significant improvement was observed in both TS-152 groups compared with those in the placebo group. Efficacy in the TS-152 groups was comparable irrespective of the dose.

In patients with active RA who had an inadequate response to MTX, TS-152 30 and 80 mg subcutaneously once every 4 weeks demonstrated significant improvement in ACR20 response rate at week 16 compared with placebo, and the efficacy in the TS-152 groups was comparable at both doses. There was no significant difference in the change from baseline in mTSS at week 24 between TS-152 and placebo groups. TS-152 was well tolerated with no notable safety concerns up to week 52 at both doses.

June. 21, 2022

https://onlinelibrary.wiley.com/doi/10.1002/art.42273

No

-

https://www.clinicaltrials.jp/file/RupBHLigd

Taisho Pharmaceutical Co., Ltd.

clinical-trials@taisho.co.jp

Taisho Pharmaceutical Co., Ltd.

clinical-trials@taisho.co.jp

completed

Sept. 04, 2018

Interventional

Multicenter study - Treatment period A Randomized, Placebo-controlled, Double-blind, Parallel-group - Treatment period B Open-label

treatment purpose

2-3

- Patients diagnosed with RA based on the American College of Rheumatology (ACR) 2010 revised criteria for classification of RA

etc.

- Patients who are observed any abnormal findings suggestive of malignant tumor, infection, or interstitial pneumonia.
- Patients with severe cardiovascular, hepatic, and/or renal diseases.

etc.

Both

Rheumatoid Arthritis (RA)

investigational material(s)
Generic name etc : TS-152
INN of investigational material : ozoralizumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : Subcutaneous injection every 4 weeks

control material(s)
Generic name etc : Placebo
INN of investigational material : Placebo
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Usage: Subcutaneous injection every 4 weeks, Dosage: No active ingredients contain

efficacy
safety
ACR20, Modified Total Sharp Score (mTSS)

safety
efficacy
ACR50, ACR70, DAS28-CRP, DAS28-ESR etc.

Aug. 28, 2018