A Protocol Based Treatment for Early and Severe Systemic Sclerosis With (Anti-CD20), Rituximab

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT00379431
First received: September 20, 2006
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Early and Severe Systemic Sclerosis
Drug: Administration of rituximab and methylprednisolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Protocol Based Treatment for Early and Severe Systemic Sclerosis With (Anti-CD20), Rituximab

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • Death [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
  • Heart failure defined as a LVEF< 30% [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
  • Lung failure defined as a resting PaO2< 60mmHg [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
  • Evolution of antibody titers. [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Deterioration, improvement or stabilisation of, disease activity score, 6-m walking distance, SHAQ, LVEF and creatinine clearance [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: November 2006
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Administration of rituximab and methylprednisolone Drug: Administration of rituximab and methylprednisolone

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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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.
  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 ClinicalTrials.gov identifier: NCT00379431

Locations
Belgium
UCL St. Luc Brussel
Brussel, Belgium
UZ Brussel
Brussel, Belgium
University Hospital Ghent
Ghent, Belgium, 9000
UZ Gasthuisberg Leuven
Leuven, Belgium
Sponsors and Collaborators
University Hospital, Ghent
Investigators
Principal Investigator: Filip De Keyser, MD, PhD University Hospital, Ghent
  More Information

Additional Information:
No publications provided by University Hospital, Ghent

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT00379431     History of Changes
Other Study ID Numbers: 2006/257
Study First Received: September 20, 2006
Last Updated: February 1, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Rituximab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014