臨床研究等提出・公開システム

A TWINSS Extension Trial to Evaluate the Safety and Tolerability of CFZ533 (Iscalimab) at Two Dose Levels Administered Subcutaneously in Patients With Sjogren's Syndrome

Study of Safety and Tolerability of CFZ533 in Patients With Sjogren's Syndrome (TWINSS Extn)

14

Demographics were mostly balanced among treatment arms. Most participants were between 18 and 64 years of age (range: 82.5% to 84.6%), female (range: 92.3% to 100%), White (range: 71.9% to 88.4%).

A total of 206 participants who have completed the core study participated in the extension study and most of them (87.4%) completed treatment in the extension study. Among participants who discontinued treatment, AE and subject decision were the main reasons for treatment discontinuation. Most participants (93.2%) completed the study follow-up. Among participants who discontinued during study follow-up, subject decision was the most frequent reason for discontinuation.

- After being rolled over from the TWINSS core study into this extension study, most participants experienced at least one AE. The overall incidence of AEs seemed to be comparable between the iscalimab 600 mg arm (83.6%) and the 300 mg arm (79.6%). However, numerically higher incident rates were observed in the iscalimab 600 mg arm for higher severity, SAEs, and AEs leading to study drug discontinuation. - Severe AEs were of single occurrence across multiple SOCs without particular trend and were predominately reported in the iscalimab 600 mg arm (8.6%), as compared to 300 mg arm (3.7%). - No deaths were reported in this study - SAEs occurred in 8.6% of participants in the iscalimab 600 mg arm as compared to 3.7% in the 300 mg arm. All SAEs by PT were reported as a single occurrence except Febrile neutropenia that was reported in 2 participants in the iscalimab 600 mg arm. - AEs leading to iscalimab discontinuation were reported for 5.3% participants in the iscalimab 600 mg arm as compared to 3.7% in the 300 mg arm. - Overall, no new safety signal was identified from this study. For detailed information on adverse events, please refer to the attached "Technical Result Summary".

[Primary outcome measures] Please refer to 'Adverse events'. [Secondary outcome measures] Please refer to the attached 'Technical Result Summary'.

Administration of iscalimab at 2 dose levels (600 mg and 300 mg s.c. Q2W) via PFS for an additional 48 weeks were generally well tolerated in participants with SjS who participated in the TWINSS core study.

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.

https://jrct.mhlw.go.jp/latest-detail/jRCT2071200072

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

Complete

Jan. 07, 2021

Interventional

non-randomized controlled trial

double blind

active control

parallel assignment

treatment purpose

1.Participants must have participated in the TWINSS core study, CCFZ533B2201, and must have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60
2.Signed informed consent must be obtained prior to participation in the Extension study (i.e. before commencement of the Week 60 assessments of the core study)
3.In the judgement of the Investigator, participants must be expected to clinically benefit from continued iscalimab therapy

1.Sjogren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness, specifically:
- Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impedes on ability to score ESSDAI domains
- Active rheumatoid arthritis (RA) that impedes on the ability to score the ESSDAI articular domain
- Systemic sclerosis
- Any other concurrent connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease) that is active and requires immunosuppressive treatment outside the scope of this trial and would impede on Sjogren's Syndrome organ domain assessments
2.Use of other investigational drugs other than iscalimab during the core study
3.Active uncontrolled viral, bacterial or other infections requiring systemic treatment at the time of enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
4.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test
5.Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 weeks after stopping of investigational drug

Both

Sjogren's Syndrome

Arm 1 - Iscalimab Dose 1
Arm 2 - Iscalimab Dose 2 and Placebo

Sjogren's Syndrome, autoimmune, ESSDAI, ESSPRI, anti-CD40, CFZ533, iscalimab, TWINSS Extension

1.Incidence of Treatment-emergent AEs (TEAEs) [ Time Frame: 60 weeks ]
2.Change in laboratory evaluations for hematology from baseline to each study visit [ Time Frame: 60 weeks ]
3.Change in laboratory evaluations for serum chemistry from baseline to each study visit [ Time Frame: 60 weeks ]
4.Change in vital sign measurements from baseline for each post-baseline visit [ Time Frame: 60 weeks ]

+81-956-33-7151

Nov. 10, 2020

Australia/Hungary