CB Proof of Concept Study in patients with Primary Sjogren’s Syndrome

Phase 1

Conditions: Primary Sjogren’s Syndrome
MedDRA version: 19.0Level: PTClassification code 10040767Term: Sjogren's syndromeSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2014-004523-51-SE

Lead Sponsor: CB Celltech, UK

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 58

Inclusion Criteria

•Subject must be between 18 years and 75 years of age
•Women of childbearing potential must agree to use a highly effective method of birth control during the study and for a period of 3 months after their final dose of study drug. Women not agreeing to use birth control must be of non-childbearing potential defined as; permanently sterile, congenitally sterile or postmenopausal for at least 2 years prior to Screening (Visit 1). Women of childbearing potential are required to have a serum pregnancy test taken at Screening (Visit 1), which is confirmed to be negative by urine testing prior to the first dose of study drug at Week 1 (Visit 2).
Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active during the study and for 3 months after the last dose of study drug. In addition female partner of childbearing potential of male subject must be willing to use a highly effective method of contraception for duration of study and for 3 months after last dose of study drug.
•Subject must meet the 2002 AECG criteria for Primary Sjogren’s Syndrome
•Subject must have a serum test positive for anti-SSA/Ro (Ro-52 and Ro-60) and/or anti SSB/La autoantibodies
•Subject must have an ESSDAI score of =5
•Subject must have an unstimulated salivary flow rate of > 0mL/5 minutes
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

•Subject has a diagnosis of any other autoimmune disease, ie, secondary Sjögren’s syndrome (eg, rheumatoid arthritis, systemic lupus erythematosus)
•Subject has a diagnosis of any other sicca syndrome
•Subject has significant fibromyalgia syndrome
•Subject has significant depression as defined by 5th edition Diagnostic and Statistical Manual of Mental Disorders.
•Subject has oral candidiasis
•Subject is female and is breast-feeding, pregnant, or plans to become pregnant or to start breastfeeding during the study or within 3 months after the final dose of the (IMP)
•Subject has evidence of an immunosuppressive state, including (HIV) infection, hypogammaglobulinemias, T-cell deficiencies, or (HTLV-1)
*Positive testing for HIV-1/2 at Screening (Visit 1)
•Subject has a history of chronic infections, including but not limited to concurrent acute or chronic viral hepatitis B (HBV) or hepatitis C (HCV) or tuberculosis (TB).
*Positive testing for HBV at Screening (Visit 1)
*Positive testing for HCV at Screening (Visit 1) *Positive test for TB at Screening (Visit 1)
•A subject with a history of a recent serious or life-threatening infection or any current signs or symptoms that may indicate a significant infection at Screening (Visit 1) to randomization, is also excluded. Subject must have completed any prior anti-infective therapy prior to the first dose of study drug with the exception of anti-infectives taken specifically for the treatment of acne, rosacea, onychomycosis, or vaginal yeast infections; for the prophylaxis of urinary tract infections; or prophylaxis for pre-surgical or pre-procedural reasons (including dental procedures). Note: minocycline may not be used for these purposes
•Subject is at a particularly high risk of significant infection due to their lifestyle and/or occupation.
•Subject has alcohol or substance abuse/dependence or other concurrent medical conditions that could confound study interpretation or affect the subject´s ability to fully participate.
•Subject has received intranasal influenza vaccine within the 8 weeks prior to Screening (Visit 1)
•Subject has significant hematologic abnormalities of hemoglobin <8.0g/dL, or white blood cell (WBC) <2000/mm3, or absolute neutrophil count <1000/mm3, or platelets <30,000/mm3 at Screening (Visit 1)
•Subject has a history of cancer
•Subject has a history of inflammatory bowel disease, peptic ulcers, or recurrent colitis including rectal bleeding
•Subject has >2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (=1.5xULN total bilirubin if known Gilbert’s syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin will be tested to identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
For randomized subjects with a baseline result >ULN for ALT, AST, ALP, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report form (eCRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at Screening, repeat the tests prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject must be discussed with the Medical Monitor.
•Subject has a history of or known

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the efficacy on overall disease activity and safety of UCB5857 added to current treatment relative to placebo in subjects with Primary Sjogren’s Syndrome.;Secondary Objective: 1) The efficacy of UCB5857 on changes:<br>- in salivary function<br>- in tear function<br>- patient reported outcomes<br>- cost effectiveness<br>2)PK profile of UCB5857 in subjects with pSS ;Primary end point(s): Change from Baseline in the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI);Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Change from Baseline in the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI)<br>2) Change from Baseline in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)<br>3) Change from Baseline in the stimulated salivary flow<br>4)Change from Baseline in the unstimulated salivary flow<br>5)Change from Baseline in Schirmer I test (without anesthesia);Timepoint(s) of evaluation of this end point: 1) Week 4 and 8<br>2) Week 4, 8 and 12<br>3) Week 4, 8 and 12<br>4) Week 4, 8 and 12<br>5) Week 12<br> <br>