Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome

NCT02067910 | Completed Phase 3 DMC

• 1 other identifier: IM101-473
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Sjögren's syndrome (pSS) is a common chronic auto-immune disease, characterised by inflammation of the exocrine glands, resulting in progressive dryness of the eyes and the mouth. Furthermore, many patients experience extraglandular symptoms such as restricting fatigue. Currently, biological agents have been introduced in various systemic autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. No biological agent has yet been approved for the treatment of pSS. In an open-label study, we have shown that abatacept treatment of pSS patients has promising results (Meiners et al., 2014). Therefore, the aim of this study is to evaluate efficacy and safety of subcutaneous abatacept treatment in pSS in a larger and randomized clinical trial.

Conditions

Sjögren's Syndrome

Keywords

Abatacept; Subcutaneous; Sjögren's syndrome; Treatment; Safety; Efficacy

Outcome Measures

Primary Outcomes (1)

• ESSDAI

  24 weeks

Secondary Outcomes (18)

• Safety parameters

  Week 4, 8, 12, 24, 28, 32, 36, 48

• ESSDAI (at time-points other than 24 weeks)

  Week 0, 4, 8, 12, 28, 32, 36, 48

• DAS28(CRP) and DAS28(ESR)

  Week 0, 4, 8, 12, 24, 28, 32, 36, 48

• Corticosteroid dose (decrease, stable, increase)

  Week 0, 4, 8, 12, 24, 28, 32, 36, 48

• Salivary gland function

  Week 0, 12, 24, 36 and 48

Study Arms (2)

Abatacept SC

ACTIVE COMPARATOR

Weekly subcutaneous administration of 125 mg Abatacept during 48 weeks

Drug: Abatacept SC

Placebo

PLACEBO COMPARATOR

First phase: Weekly subcutaneous administration of placebo during 24 weeks. Second phase: Weekly subcutaneous administration of 125 mg Abatacept during 24 weeks.

Drug: Abatacept SC

Interventions

Abatacept SC DRUG

Weekly subcutaneous administration of 125 mg Abatacept

Also known as: Subcutaneous Abatacept, Orencia

Abatacept SC; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• ESSDAI ≥ 5
• Female or male ≥ 18 years
• pSS according to the American European Consensus Group (AECG) classification criteria (6)
• 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

You may not qualify if:

• 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 tuberculosis (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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, 9700RB, Netherlands

Location

Related Publications (3)

• Meiners PM, Vissink A, Kroese FG, Spijkervet FK, Smitt-Kamminga NS, Abdulahad WH, Bulthuis-Kuiper J, Brouwer E, Arends S, Bootsma H. Abatacept treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study). Ann Rheum Dis. 2014 Jul;73(7):1393-6. doi: 10.1136/annrheumdis-2013-204653. Epub 2014 Jan 28.

  PMID: 24473674 BACKGROUND

• Steinmetz TD, Verstappen GM, Schulz SR, de Wolff L, Wilbrink R, Visser A, Terpstra J, Bootsma H, Kroese FGM. Association of Circulating Antibody-Secreting Cell Maturity With Disease Features in Primary Sjogren's Syndrome. Arthritis Rheumatol. 2023 Jun;75(6):973-983. doi: 10.1002/art.42422. Epub 2023 Mar 22.

  PMID: 36533856 DERIVED

• de Wolff L, van Nimwegen JF, Mossel E, van Zuiden GS, Stel AJ, Majoor KI, Olie L, Los LI, Vissink A, Spijkervet FKL, Verstappen GMPJ, Kroese FGM, Arends S, Bootsma H. Long-term abatacept treatment for 48 weeks in patients with primary Sjogren's syndrome: The open-label extension phase of the ASAP-III trial. Semin Arthritis Rheum. 2022 Apr;53:151955. doi: 10.1016/j.semarthrit.2022.151955. Epub 2022 Jan 10.

  PMID: 35091325 DERIVED

MeSH Terms

Conditions

Sjogren's Syndrome

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• H. Bootsma, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 20, 2014
• Study Start: August 1, 2014
• Primary Completion: February 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

NL (1)