Pilot Study of Raptiva to Treat Sjogren's Syndrome

NCT00344448 | Terminated Phase 2 Results DMC

• 2 other identifiers: 06018106-D-0181
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effect of the drug Raptiva (efalizumab) in patients with Sjögren's syndrome (SS), an autoimmune disease affecting the glands producing saliva \& tears. The cause of SS is not known, but inflammation plays an important role. Raptiva is approved by the Food and Drug Administration to treat psoriasis, an inflammatory skin disease. Patients 18 years of age \& older with SS may be eligible for this study. Candidates are screened with a history \& physical examination, chest x-ray, and oral \& eye examinations. Participants are randomly assigned to receive either Raptiva or placebo (an inactive substance that looks like Raptiva) for the first 3 months of the study. For the next 3 months, all participants receive Raptiva. Both Raptiva \& placebo are injected under the skin once a week. Evaluation during treatment \& for 2 months after treatment as follows: Full comprehensive evaluations (beginning of the study, at weeks 13 \& 25 and 2 months after treatment ends):

• Physical examination \& blood draw.
• Saliva collection done in two ways: 1) suctions cups connected to collection tubes are placed over the salivary gland ducts in the mouth and under the tongue; and 2) a sour-tasting liquid is applied to the top \& sides of the tongue at 30-second intervals to stimulate saliva production.
• Eye exam for tear gland function.
• Questionnaires about mouth \& eye dryness, energy level and overall well-being.
• Lip biopsy (screening \& week 13 visits only). A few minor salivary glands are removed for examination under a microscope. The lower lip is numbed, a small cut is made on the inside of the lip, and several glands are removed. The cut is closed with a few stitches that are removed after 5 to 7 days.
• Magnetic resonance imaging of the parotid glands (salivary glands near the ear) at weeks 1, 13 and 25. The patient lies on a stretcher that is moved into the scanner (a metal cylinder containing a strong magnetic field). The head is held in place during the scan. The study lasts about 90 minutes.
• Short evaluations at weeks 3, 5, 9, 15, 17, 21 and 1 month after treatment ends.
• Medical history \& physical examination, blood draw, evaluation for changes in symptoms and side effects, review of current medications at weeks 3, 9, 15 and 21.
• Laboratory tests, evaluation for changes in symptoms and side effects, review of current medications, saliva collection without the sour liquid and short evaluation of tear production at weeks 5 and 17.
• Blood tests at week 29

Conditions

Sjogren's Syndrome

Keywords

Adhesion Molecule; Interventional Study; Immunomodulation; Autoimmunity; Sjogren Syndrome; SS

Outcome Measures

Primary Outcomes (1)

• Response Rate at the End of the First (Blinded, Placebo Controlled) Phase at 12 Weeks

  Patient will be considered a responder if (s)he demonstrates improvement in 2 / 3 disease activity measures without worsening of the third one. 1. Salivary flow: 0.45 ml / 15 min improvement in unstimulated whole salivary flow from baseline value obtained at the study entry. 2. Salivary gland biopsy: at least 2 points improvement in the focus score on MSG biopsy 3. Tear flow: at least 30% improvement in ophthalmic Oxford grading scheme or normalization of the scale as defined by score of 0 or 2mm improvement in Schirmer test as compared with the baseline in either eye.

  3 months

Study Arms (2)

Raptiva

EXPERIMENTAL

At the beginning of the first (week 1) and second (week 13) phases, all patients will receive reduced dose of the study medication determined at 0.7 mg/kg/week. During all the subsequent administrations, all patients will receive full dose of the study medication determined at 1 mg/kg/week.

Drug: Raptiva

placebo

PLACEBO COMPARATOR

Weekly subcutaneous injection of a placebo (formulated to match the commercial vial of Raptiva in appearance and content except for the active ingredient) for the first 12 weeks of the study.

Drug: Raptiva

Interventions

Raptiva DRUG

During the first phase of the study, subjects are randomized in a double blind fashion to receive weekly subcutaneous injections of efalizumab (Raptiva) or placebo (weeks 0-12). The second 12 weeks long phase is open label with all subjects receiving weekly subcutaneous injections of efalizumab.

Also known as: efalizumab, anti-CD11a monoclonal antibody

Raptiva; placebo

Eligibility Criteria

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

You may qualify if:

• Age at entry at least 18 years
• Must give written informed consent prior to entry in the protocol.
• Must fulfill at least 4 of the 6 following criteria for Primary SS as defined by the American-European Consensus Group Sjogren's Syndrome Classification Criteria, including either item IV or VI, or fulfill 3 of the 4 objective criteria (III, IV, V, VI) \[53\] :
• Ocular symptoms (at least one):
• Dry eyes greater than 3 months
• Foreign body sensation in the eyes
• Use of artificial tears greater than 3x/day
• Oral symptoms (at least one):
• Dry mouth greater than 3 months
• Swollen salivary glands
• Need liquids to swallow dry foods
• Ocular signs (at least one):
• Schirmer test (without anesthesia) less than or equal to 5 mm/5 min
• Positive vital dye staining (van Bijsterveld greater than or equal to 4)
• Histopathology: Minor salivary gland biopsy showing focal lymphocyte sialoadenitis (focus score greater than or equal to 1 per 4 mm(2))

You may not qualify if:

• Past head and neck irradiation.
• Hepatitis B, C, HIV, or HTLV infection.
• History of lymphoma or monoclonal gammopathy of unknown significance (MGUS).
• Sarcoidosis.
• Graft-versus-host disease.
• Women of childbearing potential are required to have a negative pregnancy test at screening.
• Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control during and for a period of three months after the completion of the study.
• Any therapy with human or murine antibodies or any experimental therapy within 3 months.
• Therapy with cyclophosphamide, pulse methylprednisolone or IVIg, azathioprine, mycophenolate mofetil, oral cyclosporine or methotrexate within 4 weeks of first study treatment.
• History of rituximab therapy.
• Prednisone dose greater than or equal to 10 mg/day.
• Allergy to murine or human antibodies.
• History of anaphylaxis.
• Serum creatinine greater than 2.0 mg/dl.
• History of any malignancy.

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Skopouli FN, Moutsopoulos HM. Autoimmune epitheliitis: Sjogren's syndrome. Clin Exp Rheumatol. 1994 Nov-Dec;12 Suppl 11:S9-11.

  PMID: 7768059 BACKGROUND

• Atkinson JC, Fox PC. Sjogren's syndrome: oral and dental considerations. J Am Dent Assoc. 1993 Mar;124(3):74-6, 78-82, 84-6. doi: 10.14219/jada.archive.1993.0064.

  PMID: 8335784 BACKGROUND

• Garcia-Carrasco M, Ramos-Casals M, Rosas J, Pallares L, Calvo-Alen J, Cervera R, Font J, Ingelmo M. Primary Sjogren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore). 2002 Jul;81(4):270-80. doi: 10.1097/00005792-200207000-00003. No abstract available.

  PMID: 12169882 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sjogren's Syndrome; Autoimmune Diseases

Interventions

efalizumab

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; Immune System Diseases

Limitations and Caveats

Early termination due to serious adverse event described in psoriasis which led to the withdrawal of the drug from market.

Results Point of Contact

• Title: Gabor G Illei, Md, principal Investigator
• Organization: National Institute of Dental and Craniofacial Research

illeig@mail.nih.gov

301 496-4072

Study Officials

• Gabor G Illei, MD, PhD, MHS

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Sjogren's Syndrome Clinic

Study Record Dates

• First Submitted: June 23, 2006
• First Posted: June 26, 2006
• Study Start: June 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: December 21, 2015
• Results First Posted: December 21, 2015

Record last verified: 2015-11

Locations

US (1)