Trial Outcomes & Findings for Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren's Syndrome (NCT NCT03905525)

The study was conducted at 71 sites in 23 countries. Argentina (2), Australia (1), Austria (2), Brazil (3), Canada (3), Chile (5), Colombia (3), France (5), Germany (4), Greece (1), Hungary (3), Israel (3), Italy (3), Japan (5), Republic of Korea (1), Netherlands (2), Portugal (4), Romania (2), Russia (6), Sweden (1), Turkey (1), United Kingdom (3), United States (8).

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

ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The total score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.

The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.

The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.

The FACIT F (Functional Assessment of Chronic Illness Therapy-Fatigue) is a validated 13 item patient reported outcome measure assessing fatigue and its impact on daily functioning over the past 7 days, with total scores ranging from 0 to 52, where higher scores indicate less fatigue.

Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.

The FACIT F (Functional Assessment of Chronic Illness Therapy-Fatigue) is a validated 13 item patient reported outcome measure assessing fatigue and its impact on daily functioning over the past 7 days, with total scores ranging from 0 to 52, where higher scores indicate less fatigue.

Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.

ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The final score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.

The Impact of Dry Eye on Everyday Life (IDEEL) questionnaire is a comprehensive dry eye specific questionnaire to evaluate treatment satisfaction, symptom-related bother and impact on daily life in a population with dry eye. This study only utilized the Dry Eye Symptom-Bother module. The Dry Eye Symptom-Bother module of IDEEL is composed of a single dimension (20 items). A 4-point Likert-like scale is used: from "not at all" to "very much". Patients could also answer "I did not have this symptom / Not applicable". One item is scored on a 5-point Likert-like scale from "none of the time" to "all of the time". The range for the symptom-bother score is 0 to 100, with higher scores indicating greater symptom bother.

The distribution of adverse events in Treatment Period 1 was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg, CFZ533 300 mg, CFZ533 150 mg and placebo.

The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg - CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 600 mg 24 Weeks arm includes only patients from Placebo - CFZ533 600 mg arm, who took at least one CFZ533 600 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week 24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm, and subjects from CFZ533 150 mg - CFZ533 150 mg and CFZ533 300 mg - CFZ533 300 mg arms but only took the first or the first two loading dose(s) in period 1.

The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg and placebo.

The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg - CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 300 mg 24 Weeks includes only patients from Placebo - CFZ533 300 mg arm, who received Placebo in Period 1, and either took CFZ533 600 mg loading dose + at least two CFZ533 300 mg subsequent doses in Period 2 or missed CFZ533 600 mg loading dose and took at least one CFZ533 300 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm.

Serum samples for free light kappa (FLCκ) chains were collected and analyzed.

Serum samples for free light kappa (FLCκ) chains were collected and analyzed.

Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.

Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.

Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.

Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.

Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.

Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.