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A Multi-centre Long-term Extension Study to Assess the Safety and Efficacy of GSK3196165 in the Treatment of Rheumatoid Arthritis

Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) (contRAst X)

2916

A total of 2916 subjects were enrolled in this study and all subjects except 1 subject of Otilimab 150 mg group received at least 1 dose of investigational product. -Age: 55.4 years old (mean) -Sex: Female, 2339 subjects (80.2%) and Male, 576 subjects (19.8%) -Race: White, 2304 subjects (79.0%); Asian, 429 subjects (14.7%); American Indian or Alaska Native, 93 subjects (3.2%); Black or African American, 61 subjects (2.1%); other, 28 subjects (1.0%)

A total of 2916 subjects were enrolled. Since 1 subject in the Otilimab 150 mg group did not receive investigational product due to physician's decision, the efficacy and safety populations were 1456 subjects in the Otilimab 90 mg group and 1459 subjects in the Otilimab 150 mg group, respectively. The study was terminated at Week 145.

The incidence of deaths was 10/1456 (0.69%) in the Otilimab 90 mg group and 9/1459 (0.62%) in the Otilimab 150 mg group. The incidence of serious adverse events (SAEs) were 123/1456 subjects (8.45%) in the Otilimab 90 mg group and 114/1459 subjects (7.81%) in the Otilimab 150 mg group. SAEs reported in >= 5 subjects in any group were COVID-19 pneumonia, pneumonia, osteoarthritis, and rheumatoid arthritis. The incidence of adverse events, excluding serious adverse events, was 279/1456 subjects (19.16%) in the Otilimab 90 mg group and 308/1459 subjects (21.11%) in the Otilimab 150 mg group.

The incidence of adverse events (AEs), SAEs, and adverse events of special interests (AESIs) was 902/1456 subjects (62.0%), 123/1456 subjects (8.4%), and 120/1456 subjects (8.2%) in the Otilimab 90 mg group and 931/1459 subjects (63.8%), 114/1459 subjects (7.8%), and 95/1459 subjects (6.5%) in the Otilimab 150 mg group, respectively. -Mean (SD) changes from baseline in platelet count (10^9 cells/L) at Week 24, 48, 96, and 144 were -11.9 (66.86), -12.5 (66.47), -13.8 (60.72), and 17.0 (NA) for the Otilimab 90 mg group and -9.7 (66.82), -7.6 (71.36), -5.7 (72.81), and -37.5 (40.31) for the Otilimab 150 mg group. -Mean (SD) changes from baseline in neutrophils (10^9cells/L) at Week 24, 48, 96, and 144 were -0.348 (2.18), -0.318 (2.2215), -0.243 (1.8851), and -0.360 (NA) for the Otilimab 90 mg group and -0.390 (2.13), -0.541 (2.1426), -0.582 (2.4346), and -0.935 (0.6718) for the Otilimab 150 mg group. -Mean (SD) changes from baseline in lymphocytes (10^9cells/L) at Week 24, 48, 96, and 144 were -0.001 (0.55), -0.022 (0.5385), 0.090 (0.6453), and -0.320 (NA) for the Otilimab 90 mg group and -0.012 (0.55), -0.051 (0.5725), 0.018 (0.5816), and 0.010 (0.3253) for the Otilimab 150 mg group. -Mean (SD) changes from baseline in monocytes (10^9cells/L) at Week 24, 48, 96, and 144 were 0.003 (0.18), -0.002 (0.1871), -0.042 (0.2001), and -0.220 (NA) for the Otilimab 90 mg group and 0.00 (0.194), -0.013 (0.2461), -0.001 (0.2035), and 0.010 (0.0424) for the Otilimab 150 mg group. -Mean (SD) changes from baseline in eosinophils (10^9cells/L) at Week 24, 48, 96, and 144 were 0.027 (0.1623), 0.018 (0.1435), 0.025 (0.1725), and -0.130 (NA) for the Otilimab 90 mg group and 0.022 (0.171), 0.028 (0.1844), and 0.029 (0.1526), none for the Otilimab 150 mg group. -Mean (SD) changes from baseline in basophils (10^9cells/L) at Week 24, 48, 96, and 144 were -0.001 (0.0405), -0.004 (0.0391), -0.007 (0.0423), and 0.000 (NA) for the Otilimab 90 mg group and -0.001 (0.04), -0.006 (0.0403), -0.013 (0.0346), and 0.000 (0.0141) for the Otilimab 150 mg group. -NCI-CTCAE Grade >= 3 hematologic/clinical chemistry abnormalities were observed in the Otilimab 90 mg group: Grade 3 Hypercalcemia in 1 subject, Grade 4 hyperkalemia in 2 subjects, Grade 3 hypernatremia in 1 subject and Grade 3 creatinine increased in 1 subject; and in the Otilimab 150 mg group: Grade 4 hypernatremia in 1 subject and Grade 3 chronic kidney disease in 1 subject.

-The proportions of participants who achieved a total CDAI score of <= 10 (CDAI LDA) at Week 24, 48, 96, and 144 were 47.0%, 44.0%, 40.0%, and none, respectively, in the Otilimab 90 mg group and 46.0%, 47.0%, 47.0%, and 0.0%, respectively, in the Otilimab 150 mg group. -The proportions of participants who achieved a total CDAI score of <= 2.8 (CDAI remission) at Week 24, 48, 96, and 144 were 11.0%, 12.0%, 13.0%, and none, respectively, in the Otilimab 90 mg group and 10.0%, 9.0%, 9.0%, and 0.0%, respectively, in the Otilimab 150 mg group. -The proportion of participants achieving DAS28-CRP < 2.6 (DAS28-CRP remission) at Week 24, 48, 96, and 144 was 26.0%, 25.0%, 26.0%, and none in the Otilimab 90 mg group and 25.0%, 25.0%, 28.0%, and 0.0% in the Otilimab 150 mg group. -The proportion of participants achieving DAS28-ESR < 2.6 (DAS28-ESR remission) at Week 24, 48, 96, and 132 was 15.0%, 14.0%, 16.0%, and 0.0% in the Otilimab 90 mg group and 14.0%, 13.0%, 12.0%, and 33.0% in the Otilimab 150 mg group. -The proportions of participants who achieved remission per ACR/EULAR remission criteria (Boolean and SDAI) at Week 24, 48, 96, and 144 were 7.0%, 8.0%, 8.0%, and none, respectively, in the Otilimab 90 mg group and 6.0%, 4.0%, 9.0%, and 0.0%, respectively, in the Otilimab 150 mg group. -The mean (SD) change in CDAI total score at Week 24, 48, 96, and 144 was 13.42 (10.669), 13.85 (10.612), 14.62 (11.443), and none in the Otilimab 90 mg group and 14.26 (11.637), 14.07 (11.186), 15.22 (13.997), and 11.30 (NA) in the Otilimab 150 mg group. -The mean (SD) changes in DAS28-CRP at Week 24, 48, 96, and 144 were 3.49 (1.237), 3.51 (1.224), 3.44 (1.188), and none in the Otilimab 90 mg group and 3.55 (1.269), 3.54 (1.232), 3.52 (1.389), and 3.21 (NA) in the Otilimab 150 mg group. -Mean (SD) changes in DAS28-ESR at Week 24, 48, 96, and 132 were 3.97 (1.295), 4.02 (1.284), 3.92 (1.216), and 3.77 (NA) for the Otilimab 90 mg group and 4.01 (1.333), 4.05 (1.306), 4.04 (1.470), and 4.26 (1.560) for the Otilimab 150 mg group. -The mean (SD) change in van der Heijde mTSS score (subjects from Studies 201790 and 201791 only) at Week 24 and 48 was 23.26 (34.191) and 23.27 (33.953) for the Otilimab 90 mg group and 30.31 (40.236) and 30.34 (40.432) for the Otilimab 150 mg group.

A total of 2916 subjects were enrolled in this study and received Otilimab 90 mg or Otilimab 150 mg. One subject in the Otilimab 150 mg group did not receive investigational product due to physician's decision. The study was terminated at Week 145. The primary endpoint of the incidence of AEs, SAEs, and AESIs was 902/1456 (62.0%), 123/1456 (8.4%), and 120/1456 (8.2%) in the Otilimab 90 mg group and 931/1459 (63.8%), 114/1459 (7.8%), and 95/1459 (6.5%) in the Otilimab 150 mg group.

Aug. 08, 2024

Yes

[Plan Description] IPD for this study will be made available via the Clinical Study Data Request site. [URL] http://clinicalstudydatarequest.com

https://cdn.clinicaltrials.gov/large-docs/47/NCT04333147/Prot_000.pdf

Okawa Yasutoshi

GlaxoSmithKline K.K.

Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan

jp.gskjrct@gsk.com

Okawa Yasutoshi

GlaxoSmithKline K.K.

Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan

+81-120-561-007

jp.gskjrct@gsk.com

completed

May. 12, 2020

Interventional

randomized controlled trial double blind dose comparison control parallel assignment

treatment purpose

3

-Participants with rheumatoid arthritis who are aged >=18 years at the time of signing informed consent, who have completed one of the qualifying GSK3196165 clinical studies and who, in the opinion of the investigator, may benefit from treatment with GSK3196165.
-Body weight >=40 kilograms (kg).

Other inclusion criteria specified protocol may also be followed.

-Had study intervention permanently discontinued at any time during a qualifying study.
-Were temporarily discontinued from study intervention at the time of the final study visit of a qualifying study and, in the opinion of the investigator, participation in the extension study poses an unacceptable risk for the participant's participation.

Other exclusion criteria specified protocol may also be followed.

Both

Rheumatoid Arthritis

investigational material(s)
Generic name etc :
INN of investigational material : Otilimab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material :

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material :

safety
-Incidence of adverse events (AEs) , serious adverse events (SAEs) and adverse events of special interests (AESI) [ Time Frame: Up to 4 years ]
-Change from Baseline in platelet count, neutrophils lymphocytes, monocytes, eosinophils, and basophils (Giga cells per liter [giga cells/L]) [ Time Frame: Baseline (Day 1) and up to 4 years ]
-Proportion of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) more than or equal to (>=)Grade 3 hematological/clinical chemistry abnormalities [ Time Frame: Up to 4 years ]

efficacy
-Proportion of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=10) (CDAI Low disease activity [LDA]) at Week 24 [ Time Frame: Week 24 ]
-Proportion of participants achieving CDAI total score <=10 (CDAI LDA) at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 [ Time Frame: Week 24 ]
-Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Proportion of participants achieving Disease Activity Score using 28 joint count (DAS28)-C-reactive protein (CRP) <2.6 (DAS28-CRP Remission) at Week 24 [ Time Frame: Week 24 ]
-Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Proportion of participants with DAS28- Erythrocyte sedimentation rate (ESR)<2.6 (DAS28-ESR Remission) at Week 24 [ Time Frame: Week 24 ]
-Proportion of participants with DAS28-ESR<2.6 (DAS28-ESR Remission) at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Proportion of participants achieving American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) remission (Boolean and simplified disease activity index [SDAI]) at Week 24 [ Time Frame: Week 24 ]
-Proportion of participants achieving ACR and EULAR remission (Boolean and SDAI) at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Absolute values of CDAI total score at Week 24 [ Time Frame: Week 24 ]
-Absolute values of CDAI total score at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Absolute values of DAS28-CRP at Week 24 [ Time Frame: Week 24 ]
-Absolute values of DAS28-CRP at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Absolute values of DAS28-ESR at Week 24 [ Time Frame: Week 24 ]
-Absolute values of DAS28-ESR at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Absolute values of van der Heijde modified total sharp score (mTSS) (in participants from 201790 [NCT03980483] and 201791 [NCT03970837] only) at Week 24 [ Time Frame: Week 24 ]
-Absolute values of van der Heijde mTSS (in participants from 201790 [NCT03980483] and 201791 [NCT03970837] only) at Week 48 and every 48 weeks thereafter [ Time Frame: Week 48 and every 48 weeks thereafter, up to 4 years ]
-Other secondary outcome measures

+81-52-611-6261

May. 13, 2020