Antiphospholipid Syndrome (APS) ACTION Plaquenil

Based on the randomization, patients will be assigned to receive Hydroxychloroquine or no
treatment in addition to their standard regimen. Hydroxychloroquine dose will be
weight-adjusted: 200 mg daily for patients weighing < 60kg; and 400 mg daily (200 mg twice a
day) for patients weighing > 60kg. Hydroxychloroquine tablets will be dispensed by the study
site's pharmacy. The patient compliance will be documented by the pill counts during study
visits that will be completed every 6 months. Patients will be aware of the
hydroxychloroquine doses that they will receive.

Inclusion Criteria:

- Age 18-60

- Persistent (at least 12 weeks apart) aPL-positivity within 12 months prior to the
screening defined as:

- aCL IgG/M (> 40U, medium-to-high titer, and/or greater than the 99th percentile)
and/or

- aβ2GPI IgG/M (>40U, medium-to-high titer, and/or greater than the 99th percentile)
and/or

- Positive LA test based on the International Society of Thrombosis & Haematosis
Recommendations

Exclusion Criteria:

- History of thrombosis (arterial, venous, and/or biopsy proven microthrombosis)

- Of note, history of superficial thrombophlebitis is not an exclusion criterion.

- History of Transient Ischemic Attack Confirmed by a Neurologist

- SLE Diagnosis based on the ACR Classification Criteria > 4/11

- Other Systemic Autoimmune Diseases diagnosed based on ACR Classification Criteria
(e.g., RA, Systemic Vasculitis, Spondylarthropathy, Systemic Sclerosis, Inflammatory
Muscle Disease, Sjogren Syndrome, Mixed Connective Tissue Disorder)

- Current HCQ or another antimalarial treatment (-3 months)

- Current warfarin treatment (- 3 months)

- Current heparin therapy (- 3 months)

- Current pregnancy

- Acute seizure within 7 days prior to screening (contraindication for HCQ treatment)

- Psoriasis (contraindication for HCQ treatment)

- History of HCQ eye toxicity

- History of Hydroxychloroquine allergy

- Liver disease with AST or ALT two times of the upper limit

- Known glucose-6-phosphate dehydrogenase deficiency

- Known malignancy (with the exception of non-metastatic squamous cell and basal cell
skin carcinomas)

- Alcoholism (chronic alcohol abuse)

- Known illicit drug abuse

- Patient refusal

- Inability to comply with study and follow-up procedures