Phase IIa Trial of ALXN1007 for the Treatment of Non-criteria Manifestations of Antiphospholipid Syndrome
Condition: Antiphospholipid (aPL)-Positive
MeSH terms: Antiphospholipid Syndrome
Intervention: Study Drug- ALXN1007
Intervention description: 10 mg/kg IV q 2 weeks x 12 doses
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Antiphospholipid (aPL)-positive; Antiphospholid syndrome (APS)

Summary:

      The primary purpose of this study was to evaluate the safety and tolerability of intravenous
      (IV) ALXN1007 in persistently antiphospholipid (aPL)-positive patients with at least 1 of the
      following non-criteria manifestations of APS: aPL-nephropathy, skin ulcers and/or
      thrombocytopenia.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients with a persistent and clinically significant aPL profile

        Patients with at least 1 of the following non-criteria manifestations of APS:

          1. aPL-nephropathy (diagnosed by kidney biopsy within 12 months of Screening) confirmed
             based on the updated APS Classification Criteria recommendations, and urine protein to
             creatinine ratio > 1.0 at the time of the Screening visit and/or

          2. Skin ulcers (non-infected livedoid vasculitis-like skin ulcer and/or large skin
             ulceration resembling pyoderma gangrenosum) for at least 4 weeks prior to the
             Screening visit, diagnosed by physical examination, and/or

          3. Persistent active thrombocytopenia (diagnosed by platelet counts <100 x 103/μL and ≥20
             x 103/μL [SI: <100 x 109/L and ≥ 20 x 109/L]) and confirmed at the time of screening
             (at least 4 weeks after previous test) based on the updated APS Classification
             Criteria recommendations Patients and spouse/partner who is of childbearing potential
             must be using highly effective contraception consisting of 2 forms of birth control
             (at least 1 of which must be a barrier method) starting at Screening and continuing
             through the entire study.

        Patients with aPL-nephropathy must be receiving or agree to initiate an ACE inhibitor or
        angiotensin receptor blocker at least 4 weeks prior to initiation of ALXN1007 treatment;
        unless patient is documented to be intolerant. Patients receiving oral corticosteroids must
        be on a stable dose of ≤ 10 mg/day of prednisone or equivalent dose of another
        corticosteroid preparation for at least 4 weeks prior to the first dose of ALXN1007.
        Patients receiving immunosuppressive medications (including but not limited to
        methotrexate, hydroxychloroquine, azathioprine, cyclosporine and mycophenolate mofetil)
        must be on a stable dose for at least 4 weeks prior to the first dose of ALXN1007. Patients
        receiving oral anticoagulants or antiplatelet agents (including but not limited to aspirin)
        must be on stable doses for at least 4 weeks prior to first dose of ALXN1007.

        Patients must be willing and able to give written informed consent and to comply with all
        study visits and procedures.

        Exclusion Criteria:

        Patients meeting the ACR classification criteria for systemic lupus erythematosus, systemic
        sclerosis or other systemic autoimmune diseases other than Primary APS.

        Patients experiencing an acute thrombosis or a Major Adverse Vascular Event (MAVE) within
        12 weeks prior to first administration of ALXN1007.

        Patients with skin ulcers from causes other than aPL or who are positive for DVT or venous
        insufficiency at Screening. Patients with renal function status requiring chronic dialysis
        (defined as dialysis on a regular basis as renal replacement therapy). Patients with
        unresolved meningococcal disease or with known active bacterial, viral, fungal,
        mycobacterial or other infection. Patients that have received IVIg treatment within 4 weeks
        prior to first dose of ALXN1007. Patients that have received a course of rituximab
        (RITUXAN®) therapy within 12 months prior to first dose of ALXN1007 or have evidence of
        persistent depletion of the targeted lymphocyte population. Women who are pregnant or
        nursing.