A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome

Study Overview
=================
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.

Official Title
-----------------
A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome (RITAPS)

Conditions
-----------------
Antiphospholipid Syndrome

Intervention / Treatment
-----------------
* Drug: Rituximab


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15. | Drug: Rituximab<br>* Rituximab 1000mg IV on Days 0 and 15<br>* Other names: Rituxan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Serious and Non Serious Adverse Events | Serious and non-serious adverse events were evaluated throughout 52 weeks + additional 4 months for the patients with low B cell counts. | 52 weeks + additional 4 months if needed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy of Rituximab | Outcome measures scored as complete response(CR),partial(PR),and none(NR) at 24 weeks.For thrombocytopenia,CR defined as a platelet count of ≥150×109/μl,PR as 100-149,and NR as <100.For CVD,CR defined as the disappearance of cardiac lesions,PR as 50%improvement,and NR as no change.For skin ulcer,CR defined as disappearance,PR as 50% improvement,and NR as no change.For aPL nephropathy,CR defined as a normal serum creatinine level,inactive urinary sediment,and urinary protein:creatinine 0.5;PR as a serum cr level 15%above baseline,RBCs per high-power field 50%above baseline with no casts,50%improvement in the urinary prt:cr,and estimated GFR 10%above baseline;and NR as the absence of C/PR.For cognitive dysfunction,CR defined as normalization of the cognitive impairment index with 50%improvement,PR as abnormal index with 50%,and NR as no change. | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
antiphospholipid syndrome