E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Autoimmune condition of unknown cause where the body's own selfdefenses attack glands that secrete fluids resulting in inflammation of the glands. The inflammatory process can involve other organs. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Cohort 1
To demonstrate a dose-response of CFZ533 (iscalimab) based on change in ESSDAI from baseline at Week 24.
Cohort 2
To estimate the effect of CFZ533 (iscalimab) on the change in ESSPRI at Week 24. |
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E.2.2 | Secondary objectives of the trial |
Cohort 1
To demonstrate a dose response of iscalimab based on change in ESSPRI from baseline at Week 24
Cohort 2
To estimate the effects of iscalimab based on changes in ESSDAI from baseline at Week 24
To evaluate the efficacy of iscalimab in improving the dry eye symptoms measured by IDEEL at Week 24
Cohort 1 & 2
To estimate the effects of iscalimab based on:
- change in FACIT-F from baseline at Week 24
- change in physician's global assessment (PhGA) from baseline at Week 24
To assess:
- the effect of iscalimab in the serum Free Light Chains (FLC) levels over time
- the changes in IgG and IgM levels over time after iscalimab treatment
- the effect of iscalimab on plasma CXCL-13 over time
To assess:
- safety and tolerability of iscalimab
- immunogenicity of iscalimab
- the pharmacokinetics and dose-exposure relationship of iscalimab
To measure soluble CD40 in plasma |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
i) Salivary gland biopsy (2019-02-20, Version 00)
Biopsies will be performed for the purpose of exploring the effects of iscalimab on histopathology features of salivary gland biopsies (optional).
ii) Digital assessments: wearable sensor, cognitive and mood assessments (2019-02-20, Version 00).
Digital assessments will be performed to assess the efficacy of iscalimab in improving fatigue, cognitive and mood status digitally measured with wearable device or smartphone/tablet applications (optional assessments conducted at selected sites)
iii) Pharmacogenetics: blood samples for DNA and RNA analyses (2019-02-20, Version 00):
- The use of DNA to search for biomarkers of disease and drug action.
- The activity (the expression) of genes will be examined using RNA (or other nucleic acid) analytical technologies to examine the effect of iscalimab on transient RNA expression in blood and may support the identification of pathways/markers that characterize the disease or response of treatment with iscalimab.
The genetic research is optional. |
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E.3 | Principal inclusion criteria |
•Signed informed consent
•Male or female patient ≥ 18 years of age
•Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2017)
•Seropositive for anti-Ro/SSA antibodies
•Stimulated whole salivary flow rate of ≥ 0.1 mL/min
Inclusion criteria specific for Cohort 1:
•ESSDAI ≥ 5 within the 8 predefined organ domains
•ESSPRI score of ≥5
Inclusion criteria specific for Cohort 2:
•ESSDAI < 5 within 8 domains scored for inclusion criterion for Cohort 1
•ESSPRI fatigue subscore ≥ 5 or ESSPRI dryness subscore ≥ 5
Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
•Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness
•Use of other investigational drugs
•Prior use of B cell depleting therapies, abatacept or any other immunosuppressants unless specifically allowe be the protocol.
•Use of steroids at dose >10 mg/day.
•Uncontrolled ocular rosacea (affecting the eye adnexa), posterior blepharitis or Meibomian gland disease (this criterion applies only to patients considered for Cohort 2)
•Active viral, bacterial or other infections requiring systemic treatment
•Receipt of live/attenuated vaccine within a 2-month period prior to randomization.
•Chronic infection with hepatitis B (HBV) or hepatitis C (HCV).
•Evidence of active tuberculosis (TB) infection.
Other protocol-defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo [ Time Frame: 24 weeks ]
Cohort 1 - Efficacy
2) Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo. [ Time Frame: 24 weeks ]
Cohort 2 - Efficacy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48, 52, 56, 60
2) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48 |
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E.5.2 | Secondary end point(s) |
1) Change from baseline in ESSPRI at Week 24 [ Time Frame: 24 weeks ]
Cohort 1 - Efficacy (Patient Reported Outcomes)
2) Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24 [ Time Frame: 24 weeks ]
Cohort 1&2 - Efficacy (Patient Reported Outcomes)
3) Change from baseline in Physician Global Assessment (PhGA) at Week 24 [ Time Frame: 24 weeks ]
Cohort 1&2 - Efficacy (Clinical Outcome Measures)
4) Change from baseline in ESSDAI at Week 24 [ Time Frame: 24 weeks ]
Cohort 2 - Efficacy (Clinical Outcome Measures)
5) Proportion of subjects with at least 12 points improvement measured by score of Impact of Dry Eye on Everyday Life (IDEEL) questionnaire symptom bother module at Week 24. [ Time Frame: 24 weeks ]
Cohort 2 - Efficacy (Patient Reported Outcomes)
6) Incidence of adverse events (AEs), serious adverse events (SAEs) from baseline to Week 24 and from week 24 to the end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Safety
7) Serum Free Light Chain (FLC) levels at analysis visit up to end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Biomarkers (1)
8) Immunoglobulin IgG and IgM levels at analysis visits up to end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Biomarkers (2)
9) Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Biomarkers (3) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1), 2), 3), 4) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48
5), 8), 9) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48, 52, 56, 60
6) at baseline and repeatedly until study completion
7) at Baseline and at Weeks 4, 12, 24, 32, 48, 56, 60 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity
Tolerability |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Brazil |
Canada |
Chile |
Colombia |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Portugal |
Romania |
Russian Federation |
Slovenia |
Sweden |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS (last visit of the last subject) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |