Antiphospholipid (aPL)-Positive Clinical Trial
Official title:
An Open-Label Proof of Concept Phase IIa Trial of ALXN1007 for the Treatment of Non-criteria Manifestations of Antiphospholipid Syndrome
The primary purpose of this study is 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.
| Status | Completed |
| Enrollment | 9 |
| Est. completion date | June 2016 |
| Est. primary completion date | June 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 75 Years |
| Eligibility |
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. |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Hospital das Clínicas da Faculdade de Medicina da USP | São Paulo | Sao Paulo |
| France | Hopital Claude Huriez - CHU Lille | Lille | Nord |
| France | Hôpital Cochin | Paris | France 75679 |
| Italy | Azienda Ospedaliera di Padova | Padova | |
| Japan | Hokkaido University Hospital | Sapporo-shi | Hokkaido 060-8648 |
| United Kingdom | University College London Hospitals | London | Greater London |
| United States | O & O Alpan, LLC | Fairfax | Virginia |
| United States | University of Texas Medical Branch | Galveston | Texas |
| United States | Hospital for Special Surgery | New York | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Alexion Pharmaceuticals |
United States, Brazil, France, Italy, Japan, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | To assess the effect of ALXN1007 on aPL-nephropathy, skin ulcers and thrombocytopenia | Urine protein to creatinine ratio for patients with aPL-nephropathy. Manual measurement of ulcer area and objective analysis of digital photographs for patients with skin ulcers. Platelet count for patients with thrombocytopenia. |
Treatment Period (24 weeks) and Follow-up Period (12 weeks). | No |
| Primary | 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 | Safety will be assessed based on the incidence and severity of treatment emergent adverse events and serious adverse events. Incidence of clinical laboratory abnormalities and changes from baseline through study completion in vital signs, physical examinations, ECGs and laboratory tests will also be evaluated | Treatment Period (24 weeks) and Follow-up Period (12 weeks). | Yes |
| Secondary | To evaluate the pharmacokinetic (PK) parameters of IV ALXN1007. | Estimates of PK parameters will include, at a minimum, time to maximum observed plasma concentration (tmax), maximum observed plasma concentration (Cmax), and total body clearance (CLR). | Treatment Period (24 weeks) and Follow-up Period (12 weeks). | No |
| Secondary | To evaluate the pharmacodynamic (PD) effects of IV ALXN1007. | The PD endpoints will include changes from baseline in several complement protein levels and assessment of effect on terminal complement activity through Week 24. | Treatment Period (24 weeks) and Follow-up Period (12 weeks). | No |