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

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

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.

Study Overview

• Status: Completed
• Conditions: Antiphospholipid Syndrome
• Intervention / Treatment: Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rituximab; All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.	Drug: Rituximab; Rituximab 1000mg IV on Days 0 and 15; 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

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Doruk Erkan, MD, Hospital for Special Surgery, New York

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Hospital for Special Surgery Clinical Trials List
• Barbara Volcker Center for Women and Rheumatic Disease

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: September 28, 2007
• First Submitted That Met QC Criteria: September 28, 2007
• First Posted (Estimate): October 1, 2007

Study Record Updates

• Last Update Posted (Actual): October 31, 2017
• Last Update Submitted That Met QC Criteria: October 2, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: antiphospholipid syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease; Syndrome; Antiphospholipid Syndrome; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: IRB 27022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No