Abatacept treatment in primary Sjögrens Syndrome

• Conditions: Primary Sjögren's syndrome (pSS); MedDRA version: 16.1Level: LLTClassification code 10042846Term: Syndrome Sjogren'sSystem Organ Class: 100000004859; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2014-000417-31-NL
• Lead Sponsor: niversity Medical Center Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-20
• Last Update Posted: 14 July 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

- Signed written informed consent
- ESSDAI = 5
- Female or male = 18 years
- pSS according to the American European Consensus Group (AECG) classification criteria (6)
- Disease duration = 7 years at the moment of inclusion
- pSS proven by parotid gland biopsy with characteristic features of SS
- Women of child bearing (WOCBP) potential must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 10 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
- Sexually active fertile men must use effective birth control if their partners are WOCBP
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 66
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

- Presence of any other connective tissue disease.
- Flow rate of stimulated whole saliva =0.05 ml/min in patients without extraglandular manifestations.
- Positive pregnancy test or breast-feeding women.
- Women with a child-bearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period.
- History of alcohol or drug abuse or current alcohol or drug abuse.
- History of any malignancy in the past 5 years, including MALT lymphoma in the last 5 years, or with a current suspicion for cancer, other than non-melanoma skin cell cancers (NMSC), cured by local resection or carcinoma in situ. Existing NMSCs should be removed, the lesion site healed, and residual cancer ruled out before administration of the study drug.
- Subjects with evidence (as assessed by the investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of human immunodeficiency virus (HIV) detected during screening.
- History of chronic or recurrent serious infections. (e.g. chronic pyelonephritis, osteomyelitis or bronchiectasis).
- Subjects with serious bacterial infections within the last 3 month, unless treated and resolved with antibiotics
- Subjects with herpes zoster or cytomegalovirus that resolved less than 2 months before potential enrollment.
- Subjects at risk for TB. Specifically excluded from this study will be subjects with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (= 4 weeks).
- Subjects must not be positive for hepatitis B surface antigen.
- Subjects who are positive for hepatitis C antibody if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay.
- Subjects who have received any live vaccines within 3 months before potential enrollment.
- Underlying cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal, haematological or neurological conditions, chronic or latent infectious diseases or immune deficiency which places the patient at an unacceptable risk for participation in the study.
- Use of prednisone =10 mg less than 1 month before inclusion.
- Use of pilocarpine, hydroxychloroquine, methotrexate, cyclophosphamide, cyclosporin, azathioprine, mycophenolate mofetil (MMF) and leflunomide less than 1 month before inclusion.
- Previously treated with biological DMARDs either marketed or under investigation.
- Lab abnormalities:
a. Serum creatinine =2.8 mg/dl (250 µmol/l)
b. ASAT or ALAT outside 1.5 x upper normal range of the laboratory
c. Hb < 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females
d. Neutrophil granulocytes less than 0.5 x 109/l
e. Platelet count less than 50 x 109/l
- Any other laboratory test results that, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
- Subjects will be asked if they have allergies or adverse drug reactions. The investigator will withdraw subjects at unacceptable risk for participation from the study.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatri

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of weekly SC administration of Abatacept vs placebo on disease activity assessed with ESSDAI at 24 weeks in patients with pSS. ;Secondary Objective: To assess the efficacy of Abatacept on clinical, functional, laboratory, subjective, and histological parameters over 48 weeks in patients with pSS. <br>To evaluate the safety of abatacept, by monitoring SAE, AE, related SAE and AE, treatment discontinuation related to SAE and AE, and lab abnormalities over 48 weeks in patients with pSS.<br>;Primary end point(s): ESSDAI;Timepoint(s) of evaluation of this end point: 24 weeks