Ignite Creation Date:
2024-05-05 @ 4:54 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00344448
Status:
TERMINATED
Last Update Posted:
2015-12-21
First Post:
2006-06-23
Brief Title:
Pilot Study of Raptiva to Treat Sjogrens Syndrome
Sponsor:
National Institute of Dental and Craniofacial Research NIDCR
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Placebo Controlled Proof of Concept Study of Raptiva a Humanized Anti-CD-11a Monoclonal Antibody in Patients With Sjogrens Syndrome
Status:
TERMINATED
Status Verified Date:
2015-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Increased risk of PML associated with raptiva in other studies
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the effect of the drug Raptiva efalizumab in patients with Sjögrens 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
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
Detailed Description:
The LFA-1ICAM-1 interaction is important in migration of lymphocytes to inflammatory sites T-lymphocyte activation antigen presentation and maintaining the integrity of the immunologic synapse In both murine and human Sjogrens Syndrome increased expression of LFA-1 was found on activated lymphocytes and increased expression of ICAM-1 was present on the activated endothelial cells in the diseased salivary and lacrimal glands In animal models blockade of the LFA-1ICAM-1 interaction resulted in reduction of glandular inflammation
Raptiva efalizumab is a recombinant humanized monoclonal antibody that binds to human CD11a the alpha-subunit of Leukocyte Function Antigen-1 LFA-1 and inhibits the LFA-1ICAM-1 interaction Raptiva is an FDA-approved medication for treatment of mild-to-moderate psoriasis
In this pilot proof of concept randomized double-blind placebo-controlled study up to 25 patients with Sjogrens syndrome may be enrolled In the first double-blind phase of the study patients will be randomized and treated with weekly subcutaneous SC injections of either Raptiva 1mgkg or placebo for 12 weeks In the second open label phase all patients will be treated with weekly SC injections of Raptiva 1mgkg for another 12 weeks and then followed for an additional 8 weeks Safety will be evaluated using standard clinical and laboratory parameters To assess the potential effect of Raptiva on Sjogrens syndrome minor salivary gland biopsy oral and ocular evaluations and measurements of surrogate markers of inflammation will be compared between the Raptiva and placebo treated groups before and after the treatment Patients who either do not tolerate the drug or have worsening in their disease activity will be withdrawn from the protocol
If Raptiva is well tolerated in this study and the treatment is associated with improvement in clinical parameters of Sjogrens Syndrome further large studies of efficacy are planned
Raptiva efalizumab is a recombinant humanized monoclonal antibody that binds to human CD11a the alpha-subunit of Leukocyte Function Antigen-1 LFA-1 and inhibits the LFA-1ICAM-1 interaction Raptiva is an FDA-approved medication for treatment of mild-to-moderate psoriasis
In this pilot proof of concept randomized double-blind placebo-controlled study up to 25 patients with Sjogrens syndrome may be enrolled In the first double-blind phase of the study patients will be randomized and treated with weekly subcutaneous SC injections of either Raptiva 1mgkg or placebo for 12 weeks In the second open label phase all patients will be treated with weekly SC injections of Raptiva 1mgkg for another 12 weeks and then followed for an additional 8 weeks Safety will be evaluated using standard clinical and laboratory parameters To assess the potential effect of Raptiva on Sjogrens syndrome minor salivary gland biopsy oral and ocular evaluations and measurements of surrogate markers of inflammation will be compared between the Raptiva and placebo treated groups before and after the treatment Patients who either do not tolerate the drug or have worsening in their disease activity will be withdrawn from the protocol
If Raptiva is well tolerated in this study and the treatment is associated with improvement in clinical parameters of Sjogrens Syndrome further large studies of efficacy are planned
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-D-0181 | OTHER | The National Institutes of Health | None |