Clinical trial NCT00537290: A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome
Official title: A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome (RITAPS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Antiphospholipid Syndrome
Keywords: antiphospholipid syndrome
Lead sponsor: Hospital for Special Surgery, New York
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2007-10-01
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RITuximab AntiphosPholipid Syndrome (RITAPS) Study is designed to evaluate whether a medication called rituximab would reduce the signs and symptoms of antiphospholipid antibody (aPL) -related certain clinical problems.

Detailed description: Persistently antiphospholipid antibody (aPL)-positive patients, age 18 - 75 years of age, with anticoagulation-resistant manifestations of APS and fulfilling protocol defined study inclusion criteria will receive two doses of Rituximab, and will be followed for 6 and 12 months for clinical and safety outcomes, respectively.

Patients are eligible to take part in this study if their blood test is persistently positive for aPL and they have one or more of the aPL-related clinical problem(s) listed below: low platelet (blood cells involved in the prevention of bleeding) count; anemia (deficiency of red blood cells); heart valve disease; skin ulcers; kidney smal vessel blood clots; and/or memory problems.

Eligibility criteria: Inclusion Criteria:

* - Positive aPL profile defined as:

  * Positive lupus anticoagulant test as defined by the International Society on Thrombosis and Haemostasis, on two or more occasions, at least 12 weeks apart and/or
  * Positive anticardiolipin antibody (aCL) immunoglobulin G(Ig)G/M/A isotype, present in \> 40U, on two or more occasions, at least 12 weeks apart and/or
  * Positive anti-β2-glycoprotein-I (aβ2GPI) IgG/M/A isotype, present in \> 40U, on two or more occasions, at least 12 weeks apart

AND

- Clinical features attributable to aPL that are resistant to warfarin and/or heparin:

* Persistent thrombocytopenia and/or
* Persistent autoimmune hemolytic anemia and/or
* Cardiac valve disease and/or
* Chronic skin ulcers and/or
* Renal thrombotic microangiopathy and/or
* Cognitive dysfunction with/without white matter changes

Exclusion Criteria (selected):

* \> 4/11 American College of Rheumatology Classification Criteria for SLE
* Acute thrombosis
* History of stroke (only for patients with cognitive dysfunction)
* Positive Hepatitis B or C serology
* History of positive HIV
* Acute or chronic pancreatitis
* Treatment with any investigational agent within 4 weeks of screening
* Receipt of a live vaccine within 4 weeks prior to randomization
* Previous Treatment with Rituximab (MabThera® / Rituxan®)
* Previous treatment with Natalizumab (Tysabri®)
* Known active bacterial, viral fungal mycobacterial, or other infection
* Pregnancy
* Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
* History of psychiatric disorder that would interfere with normal participation in this protocol
* Significant cardiac or pulmonary disease

Primary outcomes:
measure: Number of Participants Experiencing Serious and Non Serious Adverse Events
timeFrame: 52 weeks + additional 4 months if needed
Secondary outcomes:
measure: The Efficacy of Rituximab
timeFrame: 24 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery
state: New York
Study officials:
affiliation: Hospital for Special Surgery, New York
name: Doruk Erkan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Erkan D, Vega J, Ramon G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum. 2013 Feb;65(2):464-71. doi: 10.1002/art.37759.
citation: Khattri S, Zandman-Goddard G, Peeva E. B-cell directed therapies in antiphospholipid antibody syndrome--new directions based on murine and human data. Autoimmun Rev. 2012 Aug;11(10):717-22. doi: 10.1016/j.autrev.2011.12.011. Epub 2012 Jan 16.