Baminercept in Sjögren's Syndrome

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID) Identifier:
First received: March 9, 2012
Last updated: August 7, 2014
Last verified: August 2014

Sjögren's syndrome is an autoimmune disorder in which a person's own immune cells attack the body's tear and salivary glands. This disease is the second most common autoimmune disorder, affects close to four million people in the U.S., and has no known cause. About one-third of patients with Sjögren's syndrome have enlarged parotid glands (the largest salivary glands, the glands that make saliva); inflammation of organs such as the lungs and joints may also occur. There is no known effective treatment other than measures that can relieve symptoms. One of the most bothersome symptoms is dryness of the eyes and mouth. Eye drops and saliva stimulants (which help make more saliva) are common treatments. When other organs are affected, symptoms are treated with corticosteroids (prednisone), non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen), hydroxychloroquine (Plaquenil®) or other medications that suppress the immune system. These drugs may curb or kill cells of the immune system, but they are not always helpful, do not cure Sjögren's syndrome, and can have many side effects.

The purpose of the study is to find out if the experimental study agent, baminercept, is effective in treating patients with Sjögren's syndrome. The study will also determine if the study agent can be safely given to patients with Sjögren's syndrome; examine how it affects symptoms of the disease; and attempt to understand how baminercept affects the underlying mechanisms of Sjögren's syndrome and the immune system.

Condition Intervention Phase
Sjögren's Syndrome
Biological: Baminercept
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial of Baminercept, a Lymphotoxin-beta Receptor Fusion Protein, for the Treatment of Primary Sjögren's Syndrome (ASJ02)

Resource links provided by NLM:

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Change in stimulated whole salivary flow between screening and week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in stimulated and unstimulated salivary flow [ Time Frame: Weeks 4, 8, 12, 18, 24, 30, 36, and 48 ] [ Designated as safety issue: No ]
  • Change in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Changes in patient self-assessment response rate for symptoms of overall dryness, fatigue, and joint pain [ Time Frame: Weeks 4, 8, 12, 18, 24, 30, 36, and 48 ] [ Designated as safety issue: No ]
  • Changes in patient symptom survey of oral and ocular dryness [ Time Frame: Weeks 4, 8, 12, 18, 24, 30, 36, and 48 ] [ Designated as safety issue: No ]
  • Changes in visual analog scale (VAS) scores for patient self-assessments of fatigue, overall dryness, and joint pain [ Time Frame: Weeks 4, 8, 12, 18, 24, 30, 36, and 48 ] [ Designated as safety issue: No ]
  • Changes in VAS scores for patient and physician global assessments of disease activity [ Time Frame: Weeks 4, 8, 12, 18, 24, 30, 36, and 48 ] [ Designated as safety issue: No ]
  • Change in tear secretion measured by the Schirmer's I test [ Time Frame: Weeks 12, 24, 48 ] [ Designated as safety issue: No ]
  • Change between pre-treatment and Week 24 in the tonsilar architecture [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Substudy endpoint - Rochester site only

  • Changes in total lymphocyte count [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Changes in serum B cell activating factor (BAFF), the cytokine LIGHT, and cytokine CXCL 13 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Changes in blood interferon signature [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Changes in focus score from labial salivary gland biopsies [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Change in serum levels of IgM and IgG anti-KLH antibodies and serum anti-pneumococcal polysaccharide antibodies [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Changes in serum levels of autoantibodies [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Changes in responses to SF-36 Health and Well-Being survey [ Time Frame: Weeks 24, 30, and 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects in each arm experiencing a Grade 3 or higher adverse event [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects in each arm experiencing a Grade 3 or higher infection [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects in each arm experiencing injection site reactions and adverse events greater than Grade 1 [ Time Frame: 24 hours after injection ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 72
Study Start Date: July 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Baminercept Biological: Baminercept
Placebo Comparator: Placebo Other: Placebo


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Has provided written informed consent
  • Between the ages of 18-75 years (inclusive)
  • Body weight ≥ 40 kg
  • Meets the revised European criteria proposed by the American-European Consensus Group for primary Sjögren's Syndrome at screening. These criteria include 3 of the following 4 items: ocular symptoms; oral symptoms; Schirmer's I test showing less than 6 mm of wetting per five minutes in at least one eye, or filamentary keratitis on slit lamp examination, or positive lissamine green staining; diminished salivary production (unstimulated whole salivary flow rate ≤ 1.5 mL/15 min); and either positive test for serum SS-A and/or SS-B antibodies or focal lymphocytic sialadenitis, with a focus score ≥ 1.0 per 4 millimeter²(mm) on minor salivary biopsy
  • Stimulated salivary flow of ≥ 0.1 mL/minute (min) (at screening)
  • Has one or more of the following systemic manifestations of Sjögren's Syndrome that are not life-threatening:

    • fatigue (as measured by > 50 mm on a 100 mm VAS)
    • joint pain (as measured by > 50 mm on a 100 mm VAS)
    • peripheral neuropathy (documented by nerve conduction velocity study)
    • interstitial lung disease (documented by radiography and/or altered pulmonary function tests
    • leukocytoclastic vasculitis
    • renal tubular acidosis
    • interstitial nephritis
    • severe parotid swelling
    • other extraglandular manifestations causing organ system dysfunction
  • If taking prednisone (or equivalent corticosteroid), the dose must be ≤ 10 mg/day and stable for at least 4 weeks prior to Screening
  • If taking hydroxychloroquine, the dose must be stable for at least 12 weeks prior to Screening
  • If taking a cholinergic stimulant (e.g. pilocarpine, cevimeline), the dose must be stable for at least 4 weeks prior to Screening
  • Subjects must agree not to become pregnant or to impregnate a female. Because of the risk involved, participants and their partners (if of reproductive potential) must use two methods of birth control. They must continue to use both methods until 6 months after stopping study drug. Two of the birth control methods listed below may be chosen:

    • Hormonal contraception
    • Male or female condoms with or without spermicide
    • Diaphragm or cervical cap with a spermicide
    • Intrauterine device (IUD)

Exclusion Criteria:

  • Has an active infection excluding superficial cutaneous fungal or viral infections
  • Has a chronic or persistent infection that might be worsened by immunosuppressive treatment (e.g., human immunodeficiency virus [HIV], hepatitis B, hepatitis C, or tuberculosis)
  • History of TB or positive intradermal skin test for purified protein derivative (PPD); positive Mantoux test defined as 10 mm of induration (size of raised bump, not redness), or equivalent positive TB test result, as per country clinical standards, during the screening period. Subjects whose PPD induration is ≥ 5 mm but < 10 mm are eligible for the study if they had a negative chest x-ray during the screening period. There must be no other clinical evidence of TB on physical examination of the subject. Note: Subjects who have had prior adequate prophylaxis treatment for latent TB with an appropriate course of isoniazid or equivalent, per country standards, are not excluded from study participation. PPD should not be administered within 6 weeks of a live-virus vaccine
  • History of recurrent significant infections or occurrence of a serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within twelve weeks prior to Day 0
  • Receipt of live vaccine within six weeks prior to Day 0
  • History or presence of primary or secondary immunodeficiency
  • History of any life-threatening allergic reactions
  • Is a pregnant or nursing female
  • Ongoing anticoagulant therapy, which is a contraindication for labial salivary biopsy or tonsil biopsy
  • Concurrent use of anticholinergic agents, such as tricyclic antidepressants, antihistamines, phenothiazines, antiparkinsonian drugs, anti-asthmatic medications, or gastrointestinal (GI) medications that cause xerostomia in more than 10% of patients
  • Treatment with any of the following within the defined period prior to Screening:

    • 2 years for rituximab
    • 24 weeks for cyclophosphamide
    • 8 weeks for azathioprine, cyclosporine, methotrexate, or mycophenolate mofetil
    • 4 weeks for intravenous immunoglobulin
    • 4 weeks for etanercept
    • 8 weeks for adalimumab
    • 12 weeks for infliximab
  • Prednisone (or equivalent corticosteroid) > 10 mg/day
  • A definite diagnosis of RA, SLE, systemic sclerosis, or dermatomyositis
  • A history of alcohol or substance abuse within 12 months of the screening visit
  • A history of head and neck radiation therapy, sarcoidosis, or graft-versus-host disease.
  • A history of malignancy, except for a resected basal or major squamous cell carcinoma, cervical dysplasia, or in situ cervical cancer Grade I, within the last five years
  • Severe pulmonary disease as manifested by one of the following at Screening:

    • Resting oxygen saturation < 92%
    • Force vital capacity (FVC) < 50% predicted
    • Diffusion lung capacity for carbon monoxide (DLCO) < 50%
  • Abnormal laboratory results for the following parameters at the screening visit:

    • Absolute neutrophil count (ANC): < 1,500/mm³,
    • Platelets: < 100,000/mm³,
    • Hemoglobin: < 9 grams (g)/deciliter (dL),
    • Serum creatinine: ≥ 2.0 mg/dL,
    • AST: > 1.5x upper limit of normal, or
    • ALT: > 1.5x upper limit of normal.
  • A psychiatric disorder rendering the subject incapable of providing informed consent.
  • Plans for foreign travel to countries other than Canada or Western Europe within the treatment period
  • Inability or unwillingness to follow the protocol
  • Any condition or treatment that, in the opinion of the investigator, places the subject at an unacceptable risk as a participant in the trial
  • Rochester substudy subjects who meet the following criteria are disqualified from enrolling in the tonsil biopsy substudy if they:

    • Have any side effects to local anesthetics (e.g., lidocaine)
    • Have any side effects to silver nitrate
    • Do not have tonsils
    • Are not able to go 48 hours without any NSAIDS
    • Are not able to go 2 weeks without acetylsalicylic acid (aspirin)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01552681

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
St. Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins Medical Institute
Baltimore, Maryland, United States, 21224
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15260
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: E. William St. Clair, MD Duke University
Study Chair: Judith A. James, MD Oklahoma Medical Research Foundation
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT01552681     History of Changes
Other Study ID Numbers: DAIT ASJ02 
Study First Received: March 9, 2012
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sjogren's Syndrome
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Dry Eye Syndromes
Eye Diseases
Immune System Diseases
Joint Diseases
Lacrimal Apparatus Diseases
Mouth Diseases
Musculoskeletal Diseases
Pathologic Processes
Rheumatic Diseases
Salivary Gland Diseases
Stomatognathic Diseases
Xerostomia processed this record on February 04, 2016