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A 48-week, 6-arm, Randomized, Double-blind, Placebo-controlled Multicenter Trial to Assess the Safety and Efficacy of Multiple CFZ533 Doses Administered Subcutaneously in Two Distinct Populations of Patients With Sjogren's Syndrome (TWINSS)

Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren's Syndrome (TWINSS)

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Cohort 1: Demographics and baseline characteristics were balanced among all treatment arms. The mean age was between 48.7 and 53.3 years, most patients were female (range: 93.0% to 95.5%), White (range: 81.4% - 88.4%). Cohort 2: Demographics and baseline characteristics were balanced between placebo and iscalimab, comparable to Cohort 1.

Cohort 1: A total of 173 patients were randomized in the study and were as per randomization ratio distributed among the four treatment arms: 43 in the placebo arm, 44 in the iscalimab 150 mg arm, 43 in the iscalimab 300 mg arm and 43 in the iscalimab 600 mg arm. Across the four treatment arms, the most common reason for discontinuation was due to AEs. Most patients (94.2%) completed Treatment Period 1 (up to Week 24) and continued to Treatment Period 2 (up to Week 48). Most patients (93.6%) completed Treatment Period 2 (up to Week 48) and continued to the Post-Treatment Follow-up Period. Cohort 2: Similarly, a total of 100 patients were randomized in the study and were as per randomization ratio distributed among the two treatment arms: 50 in the placebo arm and 50 in the iscalimab 600 mg arm. In Treatment Period 1, discontinuations were higher in the placebo arms vs the iscalimab arm (12.0% vs 4.0%) due to AEs and patient decision. Most patients (93.0%) completed Treatment Period 1 and continued to Treatment Period 2. Most patients (91.0%) completed Treatment Period 2 (up to Week 48) and continued to the Post-Treatment Follow-up Period.

Cohort 1: - In All Study periods, AEs were reported for more than 90% of patients and SAEs were reported in 12.9% of patients in the 'Any iscalimab' group. - AEs leading to discontinuation of the study treatment was overall low and occurred in 5.8% (10/171) of patients in 'Any iscalimab' group. - There were numerically higher rates of AEs with iscalimab 600 mg compared to 150 mg and 300 mg arms. - Overall, there was no apparent dose response for AEs and SAEs. Cohort 2: - In All Study periods, AEs were reported in 84.0% of patients and SAEs were reported in 11.7% of patients in the 'Any iscalimab' group. - AEs leading to discontinuation of the study treatment overall low and occurred in 3.2% (3/94) of patients in 'Any iscalimab' group. - As the exposure time for iscalimab 600 mg treated patients was twice that of the iscalimab 300 mg treated patients, the rate of severe AEs, AEs leading to discontinuation and SAEs was numerically higher on 600 mg. - Overall, there was no apparent dose response for AEs and SAEs. For detailed information on adverse events, please refer to the attached 'Technical Result Summary'.

Cohort 1: - The primary objective of a dose-response on ESSDAI change from baseline at Week 24 was met with a statistically significant dose response in the log-linear response model. ESSDAI reductions over placebo were observed with iscalimab 150 mg (LS mean=-3.0; p = 0.0025), 300 mg (LS mean=-1.4; p=0.1578) and 600 mg (LS mean=-2.9; p = 0.0037). Cohort 2: - The primary objective of the observed effect of iscalimab 600 mg on change from baseline in ESSPRI at Week 24 showed a numerical improvement over placebo (LS mean=-0.57; p=0.1210).

For the results from secondary endpoints, please refer to the attached "Technical Result Summary".

This study met its primary objective. This study suggests a potential treatment benefit of iscalimab in patients with Sjogren's syndrome. Further studies are needed in Phase 3 to further evaluate these treatment benefits.

Yes

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Maruyama Hideki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku@novartis.com

Maruyama Hideki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku@novartis.com

completed

Sept. 25, 2019

Interventional

double-blind, placebo-controlled, multicenter, randomized, pararell group

treatment purpose

2

Classification of Sjogren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2017)

Sjogren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness

Both

Sjogren Syndrome

investigational material(s)
Generic name etc :
INN of investigational material : iscalimab
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 : --- Other
Dosage and Administration for Investigational material :

Efficacy
Cohort 1 - Change in EULAR Sjogren Syndrome Disease Activity Index (ESSDAI) score
Cohort 2 - Change in EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) score

Aug. 26, 2019