Clinical trial NCT02854059: IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Purpura, Thrombotic Thrombocytopenic
Keywords: Asymptomatic antibody-mediated TTP
Lead sponsor: Hansa Biopharma AB
Sponsor class: INDUSTRY
Collaborators: name: University College London Hospitals
First posted: 2016-08-03
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events
timeFrame: From dosing until end of follow up on day 64
Secondary outcomes:
measure: Number of Patients With Change From Baseline in ADAMTS13 Activity
timeFrame: From day of dosing until end of follow up on day 64
measure: Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels
timeFrame: From day of dosing until end of follow up on day 64
measure: Number of Patients for Whom a Decreased ADAMTS13 Activity Returned to Normal Levels at Different Time-points in the Study
timeFrame: From day of dosing until end of follow up on day 64
measure: Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of IgG
timeFrame: From day of dosing until end of follow up on day 64
measure: Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies
timeFrame: From day of dosing until end of follow up on day 64
measure: Maximum Serum Concentration (Cmax) of IdeS
timeFrame: From day of dosing until day 14
measure: Time-point for Maximum Serum Concentration of IdeS
timeFrame: From day of dosing until day 14
measure: Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of F(ab')2 Fragments
timeFrame: From day of dosing until end of follow up on day 64
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College London Hospitals NHS
state: Greater London
Study officials:
affiliation: Hansa Biopharma AB
name: Elisabeth Sonesson, PhD
role: STUDY_DIRECTOR
References:
citation: Stubbs MJ, Thomas M, Vendramin C, Sonesson E, Kjellman C, Jarnum S, Stenberg Y, Elfving C, Scully M. Administration of immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) for persistent anti-ADAMTS13 antibodies in patients with thrombotic thrombocytopenic purpura in clinical remission. Br J Haematol. 2019 Jul;186(1):137-140. doi: 10.1111/bjh.15706. Epub 2018 Nov 29. No abstract available.