Phase IIa Trial of ALXN1007 for the Treatment of Non-criteria Manifestations of Antiphospholipid Syndrome

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 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.

Study Overview

• Status: Terminated
• Conditions: Antiphospholipid (aPL)-Positive
• Intervention / Treatment: Biological: Study Drug- ALXN1007

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • Hospital das Clínicas da Faculdade de Medicina da USP
• France
  • France 75679
    • Paris, France 75679, France, 75679
      • Hôpital COCHIN
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Claude Huriez - CHU Lille
• Italy
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
• Japan
  • Hokkaido 060-8648
    • Sapporo-shi, Hokkaido 060-8648, Japan, 060-8648
      • Hokkaido University Hospital
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, NW12PG
      • University College London Hospitals
• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • O & O Alpan, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1007- Open label study; ALXN1007	Biological: Study Drug- ALXN1007; 10 mg/kg IV q 2 weeks x 12 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability of Intravenous (IV) ALXN1007 as Measured by Percentage of Patients Reporting Adverse Events	Treatment Period (24 weeks)

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Investigators: Study Director: Bert Yao, M.D., Ph.D., Alexion Medical Monitor

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: April 30, 2014
• First Posted (Estimate): May 1, 2014

Study Record Updates

• Last Update Posted (Actual): July 13, 2017
• Last Update Submitted That Met QC Criteria: June 14, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Antiphospholipid (aPL)-positive; Antiphospholid syndrome (APS)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Antiphospholipid Syndrome
• Other Study ID Numbers: ALXN1007-APS-201; 2013-003588-73 (EudraCT Number)