Abatacept treatment in patients with primary Sjögren’s syndrome

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-015558-40-NL
• Date of registration: 23/12/2009
• Prospective Registration: Yes
• Primary sponsor: University Medical Center Groningen
• Public title: Abatacept treatment in patients with primary Sjögren’s syndrome
• Scientific title: Abatacept treatment in patients with primary Sjögren’s syndrome
• Date of first enrolment: 28/07/2010
• Target sample size: 15
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-015558-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
? pSS according to the revised European – U.S. criteria(22).
? Male or female ? 18 years.
? Stimulated whole saliva secretion ? 0.15 ml/min.
? Positive autoantibodies (IgM-Rf ?10 and SS-A and/or SS-B).
? Parotid gland biopsy (paraffin material and fresh frozen tissue) with characteristic features of SS performed at time of inclusion (no longer than 12 months ago).
? In female patients: use of reliable method of contraception during the study and at least until 14 weeks after the last infusion, in women of child bearing potential.
? In male patients: use of reliable method of contraception during the study and at least until 14 weeks after the last infusion by partner of patient, in case the partner of the patient is a female of child bearing potential.
? Written informed consent.
? Patients are allowed to continue artificial tears and/or artificial saliva provided that the dosage and schedule regime are stable, and that the usage will be stopped one day prior to each evaluation.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
? Disease duration ? 5 years.
? The presence of any other connective tissue disease.
? Clinically significant serious abnormalities on electrocardiography or chest X ray.
? Lab abnormalities:
o Serum creatine > 2.8 mg/dl (250 ?mol/l);
o ASAT or ALAT outside 1.5 x upper normal range of the laboratory;
o Hb < 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females;
o Neutrophil granulocytes less than 0.5 x 109/l;
o Platelet count less than 50 x 109/l.
? Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases (e.g., patients with hepatitis B or C, patent tuberculosis or latent tuberculosis non-adequately treated) or immune deficiency which places the patient at an unacceptable risk for participation in the study.
? History of cancer, including mucosa associated lymphoid tissue (MALT) lymphoma in the preceding 5 years (except adequately treated basal cell carcinoma of the skin and carcinoma in situ of the skin).
? Positive pregnancy test or breast-feeding.
? Planned major surgery (e.g. joint replacement) within the duration of the treatment period of the study.
? Serious infections in the preceding month.
? Opportunistic infection in the preceding 3 months.
? Subjects with evidence of active or latent bacterial infections at the time enrollment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection.
? Subjects with current clinical or laboratory evidence of active tuberculosis (TB).
? Subjects with a history of active TB treated within the last 3 years.
? Subjects who received treatment for active TB greater than 3 years ago may be eligible for inclusion in this study if there is documentation of the prior anti-TB treatment confirming that it was appropriate in duration and type.
? Subjects with latent TB which was not successfully treated.
? Subjects with a positive TB screening test indicative of latent TB will not be eligible for this study unless active TB infection has been ruled out and they have been initiated treatment for latent TB with isoniazid (INH) for at least 4 weeks prior to dosing of Abatacept and they have a negative chest x-ray for active TB at enrollment. Such subjects should complete 9 months of INH treatment.
? Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
? Preceding treatment with anti-TNF, rituximab or other monoclonal antibodies
? Use of prednisone and/or pilocarpine less than 2 weeks ago
? The use of hydroxychloroquine, azathioprine, cyclofosphamide, cyclosporine, MTX and other DMARDs should be discontinued at least 1 month prior to the first infusion of abatacept.
? History of alcohol or drug abuse.


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

Health Condition(s) or Problem(s) studied

Sjögren’s syndrome (SS) is a chronic, systemic, lymphoproliferative autoimmune disease affecting the exocrine glands. The salivary and lacrimal glands are most commonly affected, resulting in dry mouth and dry eyes. Extraglandular involvement can occur in SS, and includes, amongst others, pulmonary disease, renal disease and vasculitis. Moreover, almost all patients suffer from restricting fatigue.
MedDRA version: 12.0 Level: LLT Classification code 10040767 Term: Sjogren's syndrome

Intervention(s)

Trade Name: Orencia
Pharmaceutical Form: Powder for concentrate for solution for infusion

Primary Outcome(s)

Primary end point(s): primary endpoint:
- Stimulated whole salivary gland function at week 24

secundary endpoints:
- functional parameters (clinical glandular and extraglandular examination)
- laboratory parameters (e.g. B and T cell subsets, IgM-Rf)
- subjective parameters (VAS scores, MFI, SF-36)
- histological/molecular parameters

Secondary Objective: Evaluation of efficay of abatacept treatment in 15 patients with pSS on objective signs and subjective complains.

Main Objective: Evaluation of efficacy (as assessed by the stimulated whole saliva flow rate at 24 weeks) and safety of abatacept treatment in 15 patients with pSS.

Secondary ID(s)

ABACEPT1