E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sjogren’s Syndrome |
|
E.1.1.1 | Medical condition in easily understood language |
Primary Sjogren’s Syndrome |
|
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 | 19.0 |
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 |
|
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 |
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. |
|
E.2.2 | Secondary objectives of the trial |
1) The efficacy of UCB5857 on changes: - in salivary function - in tear function - patient reported outcomes 2)PK profile of UCB5857 in subjects with pSS |
|
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 |
Collection of samples for mRNA and DNA to allow for potential exploratory analyses of transcriptome biomarkers and protein biomarkers relevant to inflammatory and immune response processes or relevant to the mechanism of action of UCB5857 |
|
E.3 | Principal 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 |
|
E.4 | Principal 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 (eg, history of head and neck radiation treatment, sarcoidosis chronic graft-versus-host disease) •Subject has significant fibromyalgia syndrome as defined by the American College of Rheumatology 2010 classification criteria. •Subject has significant depression as defined by the 5th edition of the 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 investigational medicinal product (IMP) •Subject has evidence of an immunosuppressive state, including human immunodeficiency virus (HIV) infection, hypogammaglobulinemias, T-cell deficiencies, or human T-cell leukemia virus type 1 (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 in the study.•Subject has received intranasal influenza vaccine within the 8 weeks prior to Screening (Visit 1) •Subject has significant hematologic abnormalities of hemoglobin <10.0g/dL, or white blood cell (WBC) <2000/mm3, or absolute neutrophil count <1000/mm3, or platelets <100,000/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 (within 1 year prior to Screening [Visit 1]). •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 risk factors for liver disease (other than the disease under study), for example (but not limited to): bile duct disorders, hereditary condition with hepatic involvement, exposure to toxins and hepatotropic infectious agents.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline in the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) Change from Baseline in the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) 2) Change from Baseline in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI) 3) Change from Baseline in the stimulated salivary flow 4)Change from Baseline in the unstimulated salivary flow 5)Change from Baseline in Schirmer I test (without anesthesia) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 4 and 8 2) Week 4, 8 and 12 3) Week 4, 8 and 12 4) Week 4, 8 and 12 5) Week 12
|
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
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 | 2 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 29 |
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 | 15 |