臨床研究等提出・公開システム

A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO ASSESS THE EFFICACY AND SAFETY OF TOCILIZUMAB VERSUS PLACEBO IN PATIENTS WITH SYSTEMIC SCLEROSIS

Phase III Study of Tocilizumab in Patients with Systemic Sclerosis

212

81% were women, baseline mean values were age 48 years, SSc duration 23 months.

210 patients were treated [PBO, 106; TCZ, 104]

Serious adverse events were reported by 17% of PBO patients and 13% of TCZ patients.

At week 48, the primary end point (change in mRSS) was not met but improved numerically (PBO, -4.41; TCZ, -6.14; adjusted difference in least squares mean, -1.73 ; p = 0.098)

The change (least squares mean) from baseline at week 48 in ppFVC was -4.58% in PBO and -0.38% in TCZ.

The primary end point was not met; however, clinically meaningful differences in FVC were shown in this trial.

Oct. 21, 2018

https://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-for-the-treatment-of-systemic-sclerosis-results-from-a-phase-3-randomized-controlled-trial/

Yes

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

Chugai Pharmaceutical Co., Ltd.

clinical-trials@chugai-pharm.co.jp

Chugai Pharmaceutical Co., Ltd.

clinical-trials@chugai-pharm.co.jp

completed

Jan. 08, 2016

Interventional

Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase III Study

treatment purpose

3

(1)Age >= 18 years at baseline (Day1)
(2)Diagnosis of SSc, as defined using the American College of Rheumatology/EULAR criteria
(3)SSc disease duration of =< 60 months(defined as time from the first non-Raynaud phenomenon manifestation)
(4)mRSS of >= 10 and =< 35 units at screening
(5)Active disease that meets at least one of the following criteria at screening:
-Disease duration of =< 18 months defined as time from the first non-Raynaud phenomenon manifestation
-Increase in mRSS of >= 3 units compared with the most recent assessment performed within the previous 6 months
-Involvement of one new body area and an increase in mRSS of >= 2 units compared with the most recent assessment performed within the previous 6 months
-Involvement of two new body areas within the previous 6 months
-Presence of at least one tendon friction rub
(6)Uninvolved or mildly thickened skin at one of the following possible injection-site locations:
-Front, middle region of the thigh
-Abdomen, except for the 2-inch area directly around the navel
-Outer area of the upper arm(if a patient caregiver is giving the injection)

(1)Skin thickening (scleroderma) limited to areas distal to the elbows or knees at screening
(2)Rheumatic autoimmune disease other than SSc, including but not limited to RA (diagnosed using ACR/EULAR criteria), systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjogren's syndrome, and eosinophilic myalgia syndrome, as determined by the investigator
(3)Previous treatment with anti-IL6 therapy (including and not limited to TCZ)
(4)Treatment with cyclophosphamide within 6 months prior to baseline
(5)Pulmonary disease with FVC =< 55% of predicted (best of three acceptable and repeatable measurements as described in the site's Pulmonary Function Testing Manual) OR DLCO =< 45% of predicted (corrected for hemoglobin, and the average of the 2 highest acceptable and repeatable measurements as described in the Pulmonary Function Testing Manual)
(6)Class II or higher PAH, as defined by the World Health Organization
(7)Treatment with non-investigational or investigational cell-depleting therapies,
including but not limited to alemtuzumab, anti-CD4, anti-CD5, anti-CD3, anti-CD19,and anti-CD20 within 18 months of baseline; or if treatment prior to 18 months from baseline, evidence of peripheral depletion of targeted lymphocyte subset at screening
(8)History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies

Both

Systemic Sclerosis

investigational material(s)
Generic name etc : Tocilizumab
INN of investigational material : tocilizumab
Therapeutic category code : 639 Other biological preparations
Dosage and Administration for Investigational material : 162 mg/W, SC

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Placebo/W, SC

efficacy
The primary efficacy endpoint is the mean change in mRSS from baseline to Week 48.
The primary analysis population for efficacy will be the ITT population, which includes all patients who are randomized and who receive any study drug. Patients in the ITT population will be grouped according to the treatment assigned at randomization.

efficacy
(1)Difference in proportions of patients with >= 20%, >= 40%, and >= 60% improvement in mRSS at Week 48 compared with baseline
(2)Difference in mean change in FVC from baseline to Week 48
(3)Difference in mean change in HAQ-DI from baseline to Week 48
(4)Difference in mean change in Patient's Global Assessment from baseline to Week 48
(5)Difference in mean change in Physician's Global Assessment from baseline to Week 48
(6)Time to treatment failure during the 48 week double-blind treatment period
There is compared between the group of patients who received Tocilizumab 162 mg QW and the group of patients who received placebo.

July. 03, 2015