IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients

A Phase II Pilot Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics and Pharmacokinetics of IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients With Low ADAMTS13 Activity

The main purpose of this study is to evaluate safety and tolerability in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity after receiving single intravenous dose of IdeS.

Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is an IgG specific endopeptidase which cleaves IgG molecules and efficiently neutralizes Fc-mediated activities. IdeS-mediated IgG degradation constitutes a novel therapeutic principle for the treatment of IgG-driven human diseases.

In addition to assessing the safety and tolerability of IdeS the study will also assess the efficacy of IdeS to significantly increase the ADAMTS13 activity and decrease the anti-ADAMTS13 antibody levels in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity.

Inclusion Criteria:

• Age 18 years or above
• Diagnosed with acquired TTP with ADAMTS13 levels of ≤ 10 % in clinical remission and with measurable or previously confirmed ADAMTS13 antibodies

Exclusion Criteria:

• Prior malignancy within 5 years
• Test positive for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV)
• Ongoing infectious disease including P-CRP >10
• Test positive for IgE antibodies against IdeS
• Secondary cause of TTP
• Rituximab treatment or other antibody-based therapy within 7 days prior to IdeS dosing
• Treatment with investigational medicinal product within the last 12 weeks proceeding screening
• Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
• History of any other clinically significant disease or disorder which may either put the patient at increased risk because of participation in the study, or influence the results or the patient's ability to participate in the study
• Hypogammaglobulinemia defined as any values of P-total IgG less than 3 g/L
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to IdeS (e. g. streptokinase and/or staphylokinase)
• Substance abuse or other concurrent medical condition that could confound study interpretation or affect the patient's ability to tolerate or complete the study
• Breast feeding women or women with a positive pregnancy test
• Previously received IdeS treatment