臨床研究等提出・公開システム

A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study, Comparing GSK3196165 With Placebo and With Tofacitinib in Combination With Conventional Synthetic DMARDs, in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic DMARDs or Biologic DMARDs

Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Drugs (DMARDs) (contRAst 2)

1764

A total of 1625 subjects were enrolled (Global cohort). After that, the enrollment continued only in Asian countries, and a total of 139 additional subjects were enrolled (Asia cohort). A total of 1764 subjects were enrolled. One patient in the Asia cohort was enrolled but did not receive the study drug. The major patient backgrounds of the 1763 patients are as follows. -Age: 18-49 years old: 528 subjects (29.9%), 50-64 years old: 847 subjects (48.0%), >-65 years old: 388 subjects (22.0%) -Sex: Female, 1403 subjects (79.6%) and Male, 360 subjects (20.4%) -Race: White, 1202 subjects (68.2%); Asian, 429 subjects (24.3%); American Indian or Alaska Native, 105 subject (6.0%); Black or African American, 24 subjects (1.4%); Missing, 2 subjects (0.1%); Multiple, 1 subject (0.1%)

<Global cohort> Of 1625 subjects enrolled in Global cohort, 545, 539, 271, 91, 89 and 90 subjects were randomized to the otilimab 90 mg SC weekly group (Hereinafter, referred to as the otilimab 90 mg group), the otilimab 150 mg SC weekly group (Hereinafter, referred to as the otilimab 150 mg group), the tofacitinib 5 mg BID orally group (Hereinafter, referred to as the tofacitinib group), the placebo followed by otilimab 90 mg SC weekly group (Hereinafter, referred to as the placebo followed by otilimab 90 mg group), the placebo followed by otilimab 150 mg SC weekly group (Hereinafter, referred to as the placebo followed by otilimab 150 mg group) and the placebo followed by tofacitinib 5 mg BID orally group (Hereinafter, referred to as the placebo followed by tofacitinib group), respectively. The number of subjects who completed the study was 461, 447, 231, 73, 69 and 68 in the otilimab 90mg group, the otilimab 150mg group, the tofacitinib group, the placebo followed by otilimab 90 mg group, the placebo followed by otilimab 150 mg group and the placebo followed by tofacitinib group, respectively. <Asia cohort> Of 138 subjects enrolled in Asia cohort, 47, 49, 19, 6, 8 and 9 subjects were randomized to the otilimab 90 mg group, the otilimab 150 mg group, the tofacitinib group, the placebo followed by otilimab 90 mg group, the placebo followed by otilimab 150 mg group and the placebo followed by tofacitinib group, respectively. The number of subjects who completed the study was 25, 23, 15, 4, 5 and 4 in the otilimab 90mg group, the otilimab 150mg group, the tofacitinib group, the placebo followed by otilimab 90 mg group, the placebo followed by otilimab 150 mg group and the placebo followed by tofacitinib group, respectively.

A summary of adverse event in each treatment group for the following period is shown as below; otilimab 90 mg group, otilimab 150 mg group, tofacitinib group: Week 0 - Week 59, pooled placebo group: Week 0 - Week 12, placebo followed by otilimab 90 mg group, placebo followed by otilimab 150 mg group, placebo followed by tofacitinib group: Week 12 - Week 59. <Global cohort> The deaths were reported 5/545 (0.92%) in the otilimab 90mg group, 6/539 (1.11%) in the otilimab 150mg group, 2/286 (0.70%) in the tofacitinib group, 0/255 (0.00%) in the pooled placebo group, 1/85 (1.18%) in the placebo followed by otilimab 90 mg group, 1/80 (1.25%) in the placebo followed by otilimab 150 mg group and 0/67 (0.00%) in the placebo followed by tofacitinib group. The incidence of serious adverse events was 44/545 (8.07%) in the otilimab 90mg group, 43/539 (7.98%) in the otilimab 150mg group, 31/286 (10.84%) in the tofacitinib group, 6/255 (2.35%) in the pooled placebo group, 5/85 (5.88%) in the placebo followed by otilimab 90 mg group, 3/80 (3.75%) in the placebo followed by otilimab 150 mg group and 2/67 (2.99%) in the placebo followed by tofacitinib group. Major serious adverse events (>-2 patients in any treatment group) were acute myocardial infarction, cholecystitis acute, appendicitis, COVID-19, COVID-19 pneumonia, pneumonia, osteoarthritis, rheumatoid arthritis, invasive lobular breast carcinoma and pulmonary embolism. The incidence of adverse events, excluding serious events, was 233/545 (42.75%) in the otilimab 90 mg group, 208/539 (38.59%) in the otilimab 150 mg group, 105/286 (36.71%) in the tofacitinib group, 3/255 (1.18%) in the pooled placebo group, 28/85 (32.94%) in the placebo followed by otilimab 90 mg group, 31/80 (38.75%) in the placebo followed by otilimab 150 mg group and 23/67 (34.33%) in the placebo followed by tofacitinib group. <Asia cohort> No death was reported in any of treatment group in Asia cohort. The incidence of serious adverse events was 5/47 (10.64%) in the otilimab 90 mg group, 4/49 (8.16%) in the otilimab 150 mg group, 2/19 (10.53%) in the tofacitinib group, 1/23 (4.35%) in the pooled placebo group, 0/6 (0.00%) in the placebo followed by otilimab 90 mg group, 1/8 (12.50%) in the placebo followed by otilimab 150 mg group and 0/8 (0.00%) in the placebo followed by tofacitinib group. Any of these event was reported in 1 participant each. The incidence of adverse events, excluding serious events, was 28/47 (59.57%) in the otilimab 90 mg group, 39/49 (79.59%) in the otilimab 150 mg group, 18/19 (94.74%) in the tofacitinib group, 10/23 (43.48%) in the pooled placebo group, 6/6 (100.00%) in the placebo followed by otilimab 90 mg group, 5/8 (62.50%) in the placebo followed by otilimab 150 mg group and 7/8 (87.50%) in the placebo followed by tofacitinib group.

<Global cohort> The Percentage of Participants with ACR20 at Week 12 was 54.9% in the otilimab 90mg group. 54.5% in the otilimab 150mg group, 71.1% in the tofacitinib group and 32.5% in the pooled placebo group. The difference between otilimab 90 mg versus placebo at Week 12 and between otilimab 150 mg versus placebo reached statistical significance. <Asia cohort> The Percentage of Participants with ACR20 at Week 12 was 45.0% in the otilimab 90mg group, 40.0% in the otilimab 150mg group, 68.0% in the tofacitinib group and 14.0% in the pooled placebo group.

Percentage of Participants With CDAI Total Score <=10 at Week 12 was 26.5% in the otilimab 90mg group, 25.1% in the otilimab 150mg group, 36.8% in the tofacitinib group, 11.4% in the pooled placebo group. Change (SE) From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 was -0.32 (0.029) in the otilimab 90mg group, -0.31 (0.029) in the otilimab 150mg group, -0.46 (0.037) in the tofacitinib group, -0.14 (0.038) in the pooled placebo group. Percentage of Participants With CDAI Total Score <=10 at Week 12 was 13.0% in the otilimab 90mg group, 12.0% in the otilimab 150mg group, 58.0% in the tofacitinib group, 19.0% in the pooled placebo group. Change (SE) From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 -0.22(0.479) in the otilimab 90mg group, -0.25(0.537) in the otilimab 150mg group, -0.47(0.281) in the tofacitinib group, 0.02(0.577) in the pooled placebo group. Due to a change in the statistical analysis plan, non-inferiority of the Percentage of Participants with ACR20 at Week 12 between otilimab 90 mg or otilimab 150 mg and tofacitinib was not confirmed. For results of other secondary outcome measures, see ClinicalTrials.gov (NCT03970837).

A total of 1625 subjects were enrolled (Global cohort). After that, the enrollment continued only in Asian countries, and a total of 139 additional subjects were enrolled (Asia cohort). A total of 1764 subjects were enrolled. One patient in the Asia cohort was enrolled but did not receive the study drug. Of 1625 subjects enrolled in Global cohort. 545, 539, 271, 91, 89 and 90 subjects were randomized to otilimab 90 mg group, otilimab 150 mg group, tofacitinib group, placebo followed by otilimab 90 mg group

April. 26, 2024

Nov. 30, 2023

https://clinicaltrials.gov/study/NCT03970837?tab=results

Yes

IPD for this study will be made available via the Clinical Study Data Request Site

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

June. 05, 2019

Interventional

randomized controlled trial, double blind, placebocontrol, parallel assignment

treatment purpose

3

- >=18 years of age
- Has had RA for >=6 months and was not diagnosed before 16 years of age
- Has active disease, as defined by having both
- >=6/68 tender/painful joint count (TJC), and
- >=6/66 swollen joint count (SJC)
- Has at least 1 bone erosion present on hand/wrist or foot radiographs
- Has had an inadequate response to one or two of the csDMARDs:
- methotrexate (MTX) 15-25 mg/week oral or injected
- hydroxychloroquine up to 400 mg/day or chloroquine up to 250 mg/day
- sulfasalazine up to 3000 mg/day
- leflunomide up to 20 mg/day
- bucillamine up to 100 mg/day
- iguratimod up to 50 mg/day

Other inclusion criteria specified protocol may also be followed.

- History of other inflammatory rheumatologic or systemic autoimmune disorder, other than Sjogren's syndrome secondary to RA, that may confound the evaluation of the effect of the study intervention.
- Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections.
- Has received prior treatment with an antagonist of GM-CSF or its receptor or Janus kinase (JAK) inhibitors (either experimental or approved).

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 : Tofacitinib
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material :
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material :

efficacy
- Proportion of participants achieving 20% improvement in American College of Rheumatology Criteria (ACR20) at Week 12: superiority comparison with placebo [ Time Frame: Week 12 ]

safety
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 12 [ Time Frame: Week 12 ]
- Change from Baseline in HAQ-DI at Week 12 (Scores on a scale) [ Time Frame: Baseline (Day 1) and Week 12 ]
- Proportion of participants achieving ACR20 at Week 12: non-inferiority comparison with tofacitinib [ Time Frame: Week 12 ]
- Other secondary outcome measures

+81-948-29-8974

Sept. 04, 2019