Primary Sjögren's SyndromePhase 2NCT00426543
Effect of B-cell Depletion in Patients With Primary Sjögren's Syndrome
A Phase 2 study testing MabThera (rituximab) and Rituximab, Mabthera in people with Primary Sjögren's Syndrome and Xerostomia, run by University of Copenhagen at 1 site in Denmark.
Trial summary
The primary purpose of the study is to determine whether B-cell depletion with Rituximab has an effect on the oral, ocular and general disease manifestations in patients with primary Sjögren´s syndrome, that is, an effect on the symptoms of oral and ocular dryness, improvement of the glandular function and a… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Primary Sjögren's Syndrome, Xerostomia, Hyposalivation
- What is being tested?
- MabThera (rituximab) and Rituximab, Mabthera
- Type of treatment
- Injection or infusion
- How many people
- 21 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2007to Aug 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Female patients fulfilling the current American-European consensus classification criteria.
- Fertile-age female patients must use safe anticonceptional methods such as pills, mini-pills, or intrauterine spiral.
- The fertile-age females included in the study must not get pregnant in at least 12 months after the last treatment with Rituximab.
Who cannot join
- Pregnancy and lactation.
- Fertile-age females who do not use safe anticonceptional methods.
- Patients in systemic treatment with cytostatics.
- Patients who previously have been treated with Rituximab.
- Patient with an active infection that requires antibiotic treatment.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Institute of Odontology, Faculty of Health Sciences, University of Copenhagen
Copenhagen, 2200
About this study
Official title: Phase 1 Study of B-cell Depletion With Rituximab on Oral, Ocular and General Disease Manifestations in Patients With Primary Sjögren's Syndrome
The primary purpose of the study is to determine whether B-cell depletion with Rituximab has an effect on the oral, ocular and general disease manifestations in patients with primary Sjögren´s syndrome, that is, an effect on the symptoms of oral and ocular dryness, improvement of the glandular function and a beneficial effect on the general symptoms such as fatigue. The secondary purpose of the study is the investigate the underlying autoimmune and pathophysiological mechanisms in Sjögren´s syndrome.
Read the detailed description
The trial is designed as a double-blind parallel comparison between 2 infusions of 1 g Rituximab and solvent (saline) given two weeks apart, in 22 patients with the diagnosis of primary Sjögren's syndrome as based on the current American-European consensus classification criteria. The patients will be followed at the Department of Oral Medicine, Clinical Oral Physiology, Oral Pathology \& Anatomy, University of Copenhagen, the Department of Rheumatology, Rigshospitalet and at the Department of Ophthalmology, Rigshospitalet.
The primary endpoints are clinical and a response has been delineated as at least 50% improvement in score. With the provision that this occurs for any item in at least 60% of the treated patients as compared to 1% in the control patients, a power of over 80% at doubled sided significance level of 5% is found with 20 patients.The patients will be followed within this study for 6 months after Rituximab.
The study will allow the first real dynamic appraisal of the immunologic pathophysiology in Sjögren's syndrome. Hence attempts will be made to determine at the best possible level if and how Rituximab influences and possibly resets the autoimmunity both at the whole body and particularly at the local level in the salivary glands. Also the basal transport mechanism in salivary secretion which must necessarily be perturbed in Sjögren's syndrome will be scrutinized employing the best available of techniques. Every possible effort to envisage a priory, and then monitor, the decisive mechanisms has been made.
In particular this includes repetitive biopsies from the parotid glands, which will allow combining functional and structural data to reduce as much as possible random variability of crucial quantities. Also this will allow for the first time to assess the relative and combined utility of obtaining biopsies from both the parotid and labial salivary glands.
Roche A/S provide investigational medicine, but the study was initiated and is entirely controlled by the investigators.
- Conditions
- Primary Sjögren's Syndrome, Xerostomia, Hyposalivation, Keratoconjunctivitis Sicca, Fatigue
- Being tested
- MabThera (rituximab), Rituximab, Mabthera
- Keywords
- Clinical trial, Intervention study, Double-blind randomised controlled study
- Medical subject headings
- Xerostomia, Keratoconjunctivitis Sicca, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MabThera (rituximab)Drug
Also called Mabthera
1000 mg infusion twice with 14 days interval
Rituximab, MabtheraDrug
1000 mg Rituximab infusion in 500 ml isotonic sodiumchloride twice with 14 days interval
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the effect of Rituximab on subjective disease symptoms including oral dryness, ocular dryness, myoartralgia and fatigue.
Measured: Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment.
Secondary outcomes (6)
To study the effect of Rituximab: on the structural changes (focal lymphocytic infiltrates) in the labial salivary gland tissue, including changes in the T- and B-cell ratio in the infiltrates as well as in the expression of M3-receptors
Measured: Baseline and 6 months after treatment
On the salivary gland function, incl. the production and composition of whole saliva and parotid saliva, the cellular signalling mechanisms and also the distribution of M3-receptors (M3R), the expression of aquaporins,
Measured: Baseline, 1 month, 3 months and 6 months after treatment
On the circulating serum autoantibodies (anti-SSA/-SSB, rheumatoid factors) and on antibodies against the M3R and α-fodrin and on the IgG level.
Measured: Baseline, 1 month, 3 months and 6 months after treatment
On the phenotype of circulating T- and B-cells as well as cytokines and immunoregulators, especially BLyS/BAFF.
Measured: Baseline, 1 month, 3 months and 6 months after treatment
On the function of the tear glandula, including the quantity and quality of tear as well as the extent of corneal changes.
Measured: Baseline, 1 month, 3 months and 6 months after treatment
To evaluate the side-effects in relation to the use of Rituximab-/placebo treatment.
Measured: After first and second treatment and after 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2007 (estimated)
- Study startJan 2007
- Primary completionJun 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Sjögren's SyndromeStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Principal investigator, Anne Marie Lynge Pedersen, University of Copenhagen
- Investigators
- Anne Marie Lynge Pedersen, PhD, DDS, Principal investigator, Institute of Odontology, Faculty of Health Sciences, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00426543
- Sponsor's protocol ID
- KF 02 282294
- Other IDs
- EudractCT-no. 2005-004740-31
- Status last verified
- Mar 2017
- First submitted
- 23 Jan 2007
- Last updated
- 14 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ring T, Kallenbach M, Praetorius J, Nielsen S, Melgaard B. Successful treatment of a patient with primary Sjogren's syndrome with Rituximab. Clin Rheumatol. 2006 Nov;25(6):891-4. doi: 10.1007/s10067-005-0086-0. Epub 2005 Nov 8.
PubMed 16283417
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of B-cell Depletion With Rituximab on Oral, Ocular and General Disease Manifestations in Patients With Primary Sjögren's Syndrome
- ClinicalTrials.gov ID
- NCT00426543
- Acronym / sponsor ID
- KF 02 282294
- Conditions
- Primary Sjögren's Syndrome, Xerostomia, Hyposalivation, Keratoconjunctivitis Sicca, Fatigue
- Keywords
- Clinical trial, Intervention study, Double-blind randomised controlled study
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- Jan 2007
- Primary completion
- Jun 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 24 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the study is to determine whether B-cell depletion with Rituximab has an effect on the oral, ocular and general disease manifestations in patients with primary Sjögren´s syndrome, that is, an effect on the symptoms of oral and ocular dryness, improvement of the glandular function and a beneficial effect on the general symptoms such as fatigue. The secondary purpose of the study is the investigate the underlying autoimmune and pathophysiological mechanisms in Sjögren´s syndrome.
Detailed description
The trial is designed as a double-blind parallel comparison between 2 infusions of 1 g Rituximab and solvent (saline) given two weeks apart, in 22 patients with the diagnosis of primary Sjögren's syndrome as based on the current American-European consensus classification criteria. The patients will be followed at the Department of Oral Medicine, Clinical Oral Physiology, Oral Pathology \& Anatomy, University of Copenhagen, the Department of Rheumatology, Rigshospitalet and at the Department of Ophthalmology, Rigshospitalet.
The primary endpoints are clinical and a response has been delineated as at least 50% improvement in score. With the provision that this occurs for any item in at least 60% of the treated patients as compared to 1% in the control patients, a power of over 80% at doubled sided significance level of 5% is found with 20 patients.The patients will be followed within this study for 6 months after Rituximab.
The study will allow the first real dynamic appraisal of the immunologic pathophysiology in Sjögren's syndrome. Hence attempts will be made to determine at the best possible level if and how Rituximab influences and possibly resets the autoimmunity both at the whole body and particularly at the local level in the salivary glands. Also the basal transport mechanism in salivary secretion which must necessarily be perturbed in Sjögren's syndrome will be scrutinized employing the best available of techniques. Every possible effort to envisage a priory, and then monitor, the decisive mechanisms has been made.
In particular this includes repetitive biopsies from the parotid glands, which will allow combining functional and structural data to reduce as much as possible random variability of crucial quantities. Also this will allow for the first time to assess the relative and combined utility of obtaining biopsies from both the parotid and labial salivary glands.
Roche A/S provide investigational medicine, but the study was initiated and is entirely controlled by the investigators.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Female patients fulfilling the current American-European consensus classification criteria.
- Fertile-age female patients must use safe anticonceptional methods such as pills, mini-pills, or intrauterine spiral.
- The fertile-age females included in the study must not get pregnant in at least 12 months after the last treatment with Rituximab.
Key exclusion criteria (5 listed)
- Pregnancy and lactation.
- Fertile-age females who do not use safe anticonceptional methods.
- Patients in systemic treatment with cytostatics.
- Patients who previously have been treated with Rituximab.
- Patient with an active infection that requires antibiotic treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MabThera (rituximab)Also: Mabthera1000 mg infusion twice with 14 days interval | Drug | – |
| Rituximab, Mabthera1000 mg Rituximab infusion in 500 ml isotonic sodiumchloride twice with 14 days interval | Drug | – |
Primary outcome
To investigate the effect of Rituximab on subjective disease symptoms including oral dryness, ocular dryness, myoartralgia and fatigue.
Time frame: Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment.
6 secondary outcomes
To study the effect of Rituximab: on the structural changes (focal lymphocytic infiltrates) in the labial salivary gland tissue, including changes in the T- and B-cell ratio in the infiltrates as well as in the expression of M3-receptors
Time frame: Baseline and 6 months after treatment
On the salivary gland function, incl. the production and composition of whole saliva and parotid saliva, the cellular signalling mechanisms and also the distribution of M3-receptors (M3R), the expression of aquaporins,
Time frame: Baseline, 1 month, 3 months and 6 months after treatment
On the circulating serum autoantibodies (anti-SSA/-SSB, rheumatoid factors) and on antibodies against the M3R and α-fodrin and on the IgG level.
Time frame: Baseline, 1 month, 3 months and 6 months after treatment
On the phenotype of circulating T- and B-cells as well as cytokines and immunoregulators, especially BLyS/BAFF.
Time frame: Baseline, 1 month, 3 months and 6 months after treatment
On the function of the tear glandula, including the quantity and quality of tear as well as the extent of corneal changes.
Time frame: Baseline, 1 month, 3 months and 6 months after treatment
To evaluate the side-effects in relation to the use of Rituximab-/placebo treatment.
Time frame: After first and second treatment and after 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2017.
- Background: PubMed 16283417Ring T, Kallenbach M, Praetorius J, Nielsen S, Melgaard B. Successful treatment of a patient with primary Sjogren's syndrome with Rituximab. Clin Rheumatol. 2006 Nov;25(6):891-4. doi: 10.1007/s10067-005-0086-0. Epub 2005 Nov 8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Marie Lynge Pedersen, PhD, DDS principal investigator
Institute of Odontology, Faculty of Health Sciences, University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MabThera (rituximab) and Rituximab, Mabthera in people with Primary Sjögren's Syndrome and Xerostomia, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To investigate the effect of Rituximab on subjective disease symptoms including oral dryness, ocular dryness, myoartralgia and fatigue. (time frame: Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00426543, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2017.