Clinical trial NCT02128269: Phase IIa Trial of ALXN1007 for the Treatment of Non-criteria Manifestations of Antiphospholipid Syndrome
Official title: An Open-Label Proof of Concept Phase IIa Trial of ALXN1007 for the Treatment of Non-criteria Manifestations of Antiphospholipid Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Antiphospholipid (aPL)-Positive
Keywords: Antiphospholipid (aPL)-positive
Antiphospholid syndrome (APS)
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-01
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Safety and Tolerability of Intravenous (IV) ALXN1007 as Measured by Percentage of Patients Reporting Adverse Events
timeFrame: Treatment Period (24 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Fairfax
country: United States
facility: O & O Alpan, LLC
state: Virginia
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da USP
state: Sao Paulo
city: Paris
country: France
facility: Hôpital Cochin
state: France 75679
city: Lille
country: France
facility: Hopital Claude Huriez - CHU Lille
state: Nord
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido 060-8648
city: London
country: United Kingdom
facility: University College London Hospitals
state: Greater London
Study officials:
affiliation: Alexion Medical Monitor
name: Bert Yao, M.D., Ph.D.
role: STUDY_DIRECTOR
References: