Study in patients with primary Sjögren’s syndrome with the aim to assess safety, tolerability, pharmacokinetics (way the body absorbs, distributes, and gets rid of the drug) and preliminary efficacy of CFZ533

• Register: EUCTR
• Last refreshed on: 11 June 2018
• Main ID: EUCTR2013-004808-19-DE
• Date of registration: 07/12/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study in patients with primary Sjögren’s syndrome with the aim to assess safety, tolerability, pharmacokinetics (way the body absorbs, distributes, and gets rid of the drug) and preliminary efficacy of CFZ533
• Scientific title: A multi-center, randomized, double-blind, placebo-controlled, parallel group study to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of CFZ533 in patients with primary Sjögren’s syndrome - Safety, pharmacokinetics and preliminary efficacy study of CFZ533 in patients with primary Sjögren's
• Date of first enrolment: 05/02/2016
• Target sample size: 66
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004808-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: open-label in part 2 and in entire cohort 3; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: placebo is not used in Cohort 3; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Hungary, Switzerland, United Kingdom, United States

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
• Written informed consent must be obtained before any assessment is performed;
• Male and female patients 18 to 75 years of age included;
• Subjects must have a body weight of 50 – 150 kg (inclusive);
• Diagnosis of primary Sjögren’s syndrome according to revised EU/US consensus criteria (Vitali et al 2002);
• Moderate to severe disease activity as determined by ESSDAI score = 6;
• Presence of autoantibodies at screening as determined by any of the following:
? Elevated serum titers of ANA (= 1:160) and positive rheumatoid factor (RF); or,
? Positive anti-SSA
• Stimulated whole salivary flow rate > 0 mL/min for Cohort 1 and 2;
unstimulated whole salivary flow rate > 0 mL/min for Cohort 3.
• If the patient is on oral glucocorticoid treatment at screening, the dose must NOT exceed 10 mg prednisone or equivalent per day, and must be stable for at least 2 weeks prior to randomization and for the duration of the study;
• If the patient is on chloroquine or hydroxychloroquine at screening, the dose must be stable for at least 4 weeks prior to randomization and for the duration of the study;
• If the patient is treated with oral or parenteral methotrexate at screening, the dose must NOT exceed 25 mg per week for at least 3 months prior to randomization and must be stable for the duration of the study;
• If the patient is treated with oral azathioprine at screening, the dose must NOT exceed 100 mg per day for at least 3 months prior to randomization and must be stable for the duration of the study;
• Subject must be able to communicate well
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 58
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion criteria:
• Secondary Sjögren’s syndrome. Patients with laboratory or clinical signs of another connective tissue disease (e.g., systemic lupus erythematous) may be eligible at the investigators discretion;
• Use other investigational drugs at the time of enrollment, or is within five half-lives of using other investigational drugs or longer if required by local regulations, at the time of enrollment;
• History of hypersensitivity to study drug or to drugs of similar chemical classes;
• Patients having received the following treatments (within given timeframe before randomization):
? Oral or i.v. cyclosphosphamide treatment within 6 months;
? i.v. corticosteroid bolus with dose > 1 mg/kg within 3 months;
? Rituximab within 12 months. For patient who received rituximab earlier, B cell count should be within normal range;
? Belimumab within 6 month;
? Any other biologic within 1 month or five times the half-life, whichever is longer;
? Any other immunosuppressives (despite methotrexate, glucocorticoids, and
hydroxychloroquine on stable doses as described in the inclusion criteria 8, 9, 10, 11) such as cyclosporine A or mycophenolate within 3 months;
• Patients where the primary cause of sicca symptoms (e.g. dry mouth, dry eyes) as judged by the investigator, is attributable to a medication used regularly or intermittently (rather than to primary Sjogren`s syndrome)
• Patients who are at significant risk for thromboembolic events as judged by the investigator or have any one of the following:
? History of either thrombosis or 3 or more spontaneous abortions with or without the presence of anti-cardiolipin autoantibodies;
? Presence of lupus anticoagulant or prolonged partial thromboplastin time (PTT);
• Pancreatic injury or pancreatitis as indicated by abnormal signs or symptoms of pancreatitis or clinically significant elevations in amylase or lipase;
• History or presence of any medically significant cardiac condition which according to the investigator may jeopardize the patient in case of participation in the study, including ischemic heart disease, heart failure, cardiomyopathy, myocardial infarction or stroke;
• Sitting vital signs outside of the following ranges at screening or baseline: body temperature: 35.0 - 37.5°C, systolic blood pressure: 90 - 145 mmHg, diastolic blood pressure: 50 - 90 mmHg, pulse rate 50 - 100 bpm.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases;
• Signs or symptoms of a clinically significant systemic viral, bacterial or fungal infection within 30 days of randomization;

Other protocol defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

primary Sjögren’s syndrome
MedDRA version: 20.0 Level: PT Classification code 10040767 Term: Sjogren's syndrome System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: CFZ533
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not yet established
Current Sponsor code: CFZ533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: • To assess the safety and tolerability of multiple subcutaneous doses of CFZ533 in patients with primary Sjögren’s syndrome as measured by adverse events (AEs).
• To compare the effect of multiple subcutaneous doses of CFZ533 versus placebo on the clinical disease activity of primary Sjögren’s syndrome patients as measured by the change of an EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) after 12 weeks treatment.
• To assess the pharmacokinetics of multiple subcutaneous doses and multiple intravenous infusion of CFZ533 in primary Sjögren’s syndrome patients.

Other protocol defined inclusion criteria may apply;

Main Objective: • To assess the safety and tolerability of multiple intravenous infusion of CFZ533 in patients with primary Sjögren’s syndrome as measured by adverse events (AEs).
• To compare the effect of multiple intravenous infusion of CFZ533 versus placebo on the clinical disease activity of primary Sjögren’s syndrome patients as measured by the change of an EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) after 12 weeks treatment.

Primary end point(s): a. adverse event (AE) monitoring
b. change of an EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) after 12 weeks treatment

Timepoint(s) of evaluation of this end point: a. from screening to End Of Study (EOS) for all AEs/ until 30 days after
EOS for SAEs
b. at week 13

For further information, please refer to the Assessment schedule in the protocol

Secondary Outcome(s)

Secondary end point(s): a. Pharmacokinetics parameters
b. Effect on self-reported outcomes as measured by the EULAR Sjögren’s Syndrome Patient Reported Intensity (ESSPRI), the Short Form (36) Health Survey (SF-36) and the Multidimensional Fatigue Inventory (MFI) Questionnaire after 12 weeks treatment.
c. Changes in the physician global assessment of the patient’s overall disease activity as recorded by a visual analog scale (VAS) after 12 weeks treatment.
d. Changes in the patients global assessment of their disease activity as recorded by a VAS after 12 weeks treatment.

Timepoint(s) of evaluation of this end point: a. Weekly
b. At week 13
c. At week 13
d. At week 13

For further information, please refer to the Assessment schedule in the protocol

Secondary ID(s)

2013-004808-19-GB

CCFZ533X2203

Source(s) of Monetary Support

Novartis Pharma Services AG