Early and Severe Systemic SclerosisPhase 2NCT00379431
A Protocol Based Treatment for Early and Severe Systemic Sclerosis With (Anti-CD20), Rituximab
A Phase 2 study testing Administration of rituximab and methylprednisolone in people with Early and Severe Systemic Sclerosis, run by University Hospital, Ghent at 4 sites in Belgium.
Trial summary
Rituximab 1000 mg i.v. will be given on day 1 and 15, week 26 - 28, together with a corticosteroid regimen consisting of methylprednisolone 100 mg i.v. 30 minutes prior to both infusions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early and Severe Systemic Sclerosis
- What is being tested?
- Administration of rituximab and methylprednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesBelgium
- Study dates
- 27 Nov 2006to 2 Feb 2009
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female >= 18 years
- SSc according to the ARA criteria for systemic sclerosis
- Disease duration less than 4 years (from the appearance of skin changes (oedema, fibrosis)
- Inadequate response to methotrexate (at least 12 weeks 10 mg/w, except if not tolerated
- Antibodies specific for systemic sclerosis: anti-topoisomerase; anti-centromere antibodies
- Severe disease defined by either one of the following: a modified Rodnan skin score (TSS° >= 14 ), disease activity score >= 3
- Contraception for women with childbearing potential. Sexual abstinence is an alternative to contraception.
- Patient has signed informed consent.
Who cannot join
- disease duration more than 4 years
- FVC <= 50%
- LVEF <= 40% of predicted value
- DLCO <= 40% of predicted value
- Lack of peripheral venous access
- Pregnancy or breast feeding
Show all 24Show fewer
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease), evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine or gastrointestinal disorders which, in the investigator's opinion, would preclude patient participation
- Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
- Known active infection of any kind (excluding fungal infections of mail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to baseline.
- History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline.
- History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to screening).
- History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured).
- History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins.
- Concurrent treatment with any biologic agent or DMARD other than MTX. Treatment must be discontinued 14 days prior to baseline , except for the following: azathioprine for ≥ 28 days; leflunomide for ≥ 8 weeks (or ≥ 14 days after 11 days of standard cholestyramine or activated charcoal washout); infliximab ≥ 8 weeks; adalimumab ≥ weeks.
- Previous treatment with > 1 biological agent.
- Previous treatment with any cell depleting therapies, including investigational agents.
- Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (xhich ever is the longer).
- Receipt of any vaccine within 28 days prior to baseline
- Intolerance or contraindications to i.v. glucocorticoids.
- Positive serum human chorionic gonadotropin (hCG) measured at screening or a positive pregnancy test prior to the first rituximab infusion.
- Positive tests for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.
- Hemoglobin < 8.0 g/dL.
- Concentrations of serum IgG and/or IgM below 5.0 and 0.40 mg/mL, respectively.
- Absolute neutrophil count (ANC) < 1.5 X 10³/µL.
Trial locations and contacts
4 sites in 1 country.
Belgium4 sites
UCL St. Luc Brussel
Brussels
UZ Brussel
Brussels
University Hospital Ghent
Ghent, 9000
UZ Gasthuisberg Leuven
Leuven
About this study
Rituximab 1000 mg i.v. will be given on day 1 and 15, week 26 - 28, together with a corticosteroid regimen consisting of methylprednisolone 100 mg i.v. 30 minutes prior to both infusions.
- Conditions
- Early and Severe Systemic Sclerosis
- Being tested
- Administration of rituximab and methylprednisolone
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of rituximab and methylprednisoloneDrug
Rituximab:
Pharmaceutical form: Concentrate for solution for infusion. Maximum duration of treatment: 28 weeks Maximum dose allowed: 2000 mg (use of total dose) Route of administration: intravenous use.
| Study group | Role | What they receive |
|---|---|---|
| Administration of rituximab and methylprednisolone | Experimental | Not described Receives: Drug: Administration of rituximab and methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death
Measured: 28 weeks
Heart failure defined as a LVEF< 30%
Measured: 28 weeks
Lung failure defined as a resting PaO2< 60mmHg
Measured: 28 weeks
Evolution of antibody titers.
Measured: 28 weeks
Deterioration, improvement or stabilisation of, disease activity score, 6-m walking distance, SHAQ, LVEF and creatinine clearance
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2006 (estimated)
- Study start27 Nov 2006
- Primary completion2 Feb 2009
- Study completion2 Feb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Early and Severe Systemic SclerosisStudies of the same condition, open and under way.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Filip De Keyser, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00379431
- Sponsor's protocol ID
- 2006/257
- Status last verified
- Dec 2022
- First submitted
- 20 Sep 2006
- Last updated
- 20 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Melsens K, De Keyser F, Decuman S, Brusselle G, De Pauw M, Deschepper E, De Wilde K, Elewaut D, Piette Y, Vandecasteele E, Smith V. Assessment of sensitivity to change of the European Scleroderma Study Group activity index. Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):148-151. Epub 2016 Jul 18.
PubMed 27463733Smith V, Pizzorni C, Riccieri V, Decuman S, Brusselle G, DE Pauw M, Deschepper E, Piette Y, Ruaro B, Sulli A, Vandecasteele E, Melsens K, DE Keyser F, Cutolo M. Stabilization of Microcirculation in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement following Rituximab Treatment: An Open-label Study. J Rheumatol. 2016 May;43(5):995-6. doi: 10.3899/jrheum.151018. No abstract available.
PubMed 27134280Bonroy C, Smith V, Deschepper E, De Keyser F, Devreese K. Specific Antinuclear Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis Are Associated with Improvement of Skin Thickening. J Rheumatol. 2016 Jan;43(1):247-9. doi: 10.3899/jrheum.150105. No abstract available.
PubMed 26724322Smith V, Piette Y, van Praet JT, Decuman S, Deschepper E, Elewaut D, De Keyser F. Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. J Rheumatol. 2013 Jan;40(1):52-7. doi: 10.3899/jrheum.120778. Epub 2012 Nov 1.
PubMed 23118116Smith V, Van Praet JT, Vandooren B, Van der Cruyssen B, Naeyaert JM, Decuman S, Elewaut D, De Keyser F. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis. 2010 Jan;69(1):193-7. doi: 10.1136/ard.2008.095463.
PubMed 19103636
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Protocol Based Treatment for Early and Severe Systemic Sclerosis With (Anti-CD20), Rituximab
- ClinicalTrials.gov ID
- NCT00379431
- Acronym / sponsor ID
- 2006/257
- Conditions
- Early and Severe Systemic Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Study start
- 27 Nov 2006 (actual)
- Primary completion
- 2 Feb 2009 (actual)
- Study completion
- 2 Feb 2009 (actual)
- First posted
- 21 Sep 2006 (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.
Rituximab 1000 mg i.v. will be given on day 1 and 15, week 26 - 28, together with a corticosteroid regimen consisting of methylprednisolone 100 mg i.v. 30 minutes prior to both infusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Administration of rituximab and methylprednisolone | Experimental | Drug: Administration of rituximab and methylprednisolone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- male or female >= 18 years
- SSc according to the ARA criteria for systemic sclerosis
- Disease duration less than 4 years (from the appearance of skin changes (oedema, fibrosis)
- Inadequate response to methotrexate (at least 12 weeks 10 mg/w, except if not tolerated
- Antibodies specific for systemic sclerosis: anti-topoisomerase; anti-centromere antibodies
Key exclusion criteria (24 listed)
- disease duration more than 4 years
- FVC <= 50%
- LVEF <= 40% of predicted value
- DLCO <= 40% of predicted value
- Lack of peripheral venous access
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 |
|---|---|---|
| Administration of rituximab and methylprednisoloneRituximab: Pharmaceutical form: Concentrate for solution for infusion. Maximum duration of treatment: 28 weeks Maximum dose allowed: 2000 mg (use of total dose) Route of administration: intravenous use. | Drug | Administration of rituximab and methylprednisolone |
Primary outcome
Death
Time frame: 28 weeks
Heart failure defined as a LVEF< 30%
Time frame: 28 weeks
Lung failure defined as a resting PaO2< 60mmHg
Time frame: 28 weeks
Evolution of antibody titers.
Time frame: 28 weeks
Deterioration, improvement or stabilisation of, disease activity score, 6-m walking distance, SHAQ, LVEF and creatinine clearance
Time frame: 28 weeks
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 20 Dec 2022.
- Derived from this study: PubMed 27463733Melsens K, De Keyser F, Decuman S, Brusselle G, De Pauw M, Deschepper E, De Wilde K, Elewaut D, Piette Y, Vandecasteele E, Smith V. Assessment of sensitivity to change of the European Scleroderma Study Group activity index. Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):148-151. Epub 2016 Jul 18.
- Derived from this study: PubMed 27134280Smith V, Pizzorni C, Riccieri V, Decuman S, Brusselle G, DE Pauw M, Deschepper E, Piette Y, Ruaro B, Sulli A, Vandecasteele E, Melsens K, DE Keyser F, Cutolo M. Stabilization of Microcirculation in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement following Rituximab Treatment: An Open-label Study. J Rheumatol. 2016 May;43(5):995-6. doi: 10.3899/jrheum.151018. No abstract available.
- Derived from this study: PubMed 26724322Bonroy C, Smith V, Deschepper E, De Keyser F, Devreese K. Specific Antinuclear Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis Are Associated with Improvement of Skin Thickening. J Rheumatol. 2016 Jan;43(1):247-9. doi: 10.3899/jrheum.150105. No abstract available.
- Derived from this study: PubMed 23118116Smith V, Piette Y, van Praet JT, Decuman S, Deschepper E, Elewaut D, De Keyser F. Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. J Rheumatol. 2013 Jan;40(1):52-7. doi: 10.3899/jrheum.120778. Epub 2012 Nov 1.
- Derived from this study: PubMed 19103636Smith V, Van Praet JT, Vandooren B, Van der Cruyssen B, Naeyaert JM, Decuman S, Elewaut D, De Keyser F. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis. 2010 Jan;69(1):193-7. doi: 10.1136/ard.2008.095463.
- Website University Hospital GhentLink provided by the sponsor.
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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.
Filip De Keyser, MD, PhD principal investigator
University Hospital, Ghent
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Administration of rituximab and methylprednisolone in people with Early and Severe Systemic Sclerosis, run by University Hospital, Ghent at 4 sites in Belgium.
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 8 inclusion and 24 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 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium. 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?
Death (time frame: 28 weeks). The study lists 5 primary outcomes in all. 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 NCT00379431, which also lists 5 linked publications.
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 20 Dec 2022.