Antiphospholipid Syndrome
Conditions
Keywords
antiphospholipid syndrome
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.
Interventions
DRUGRituximab
Rituximab 1000mg IV on Days 0 and 15
Sponsors
Genentech, Inc.
Hospital for Special Surgery, New York
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Serious and Non Serious Adverse Events | 52 weeks + additional 4 months if needed | Serious and non-serious adverse events were evaluated throughout 52 weeks + additional 4 months for the patients with low B cell counts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Efficacy of Rituximab | 24 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Patients who were ≥18 years of age, did not have other systemic autoimmune diseases, and fulfilled at least one of the laboratory criteria and one of the clinical criteria were eligible for inclusion in the study.
Pre-assignment details
Laboratory criteria defined as positive results of a LAC test, positive aCL IgG/IgM/IgA isotype (≥40), and/or positive anti-β2GPI IgG/IgM/IgA isotype (≥40) on 2 or more occasions, at least 12 weeks apart. Clinical criteria defined as 1)persistent thrombocytopenia 2)Cardiovascular disease 3)skin ulcer 4)aPL nephropathy 5) cognitive dysfunction.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Rituximab: Rituximab 1000mg IV on Days 0 and 15 | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 40.5 years STANDARD_DEVIATION 13.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 17 / 19 |
| serious Total, serious adverse events | 12 / 19 |
Outcome results
Primary
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.
Time frame: 52 weeks + additional 4 months if needed
Population: All patients enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab | Number of Participants Experiencing Serious and Non Serious Adverse Events | 19 Participants |
Secondary
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.
Time frame: 24 weeks
Population: All patients enrolled in the study
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab | The Efficacy of Rituximab | Complete Response | 7 Participants |
| Rituximab | The Efficacy of Rituximab | Could not tolerate the infusion (not evaluated) | 2 Participants |
| Rituximab | The Efficacy of Rituximab | Partial Response | 4 Participants |
| Rituximab | The Efficacy of Rituximab | No Response | 6 Participants |