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

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

Sponsors

Lead sponsor: Hansa Biopharma AB

Collaborator: University College London Hospitals

Source Hansa Biopharma AB
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.

Overall Status Terminated
Start Date September 2016
Completion Date January 2017
Primary Completion Date January 2017
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events From dosing until end of follow up on day 64
Secondary Outcome
Measure Time Frame
Number of Patients With Change From Baseline in ADAMTS13 Activity From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels From day of dosing until end of follow up on day 64
Number of Patients for Whom a Decreased ADAMTS13 Activity Returned to Normal Levels at Different Time-points in the Study From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of IgG From day of dosing until end of follow up on day 64
Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies From day of dosing until end of follow up on day 64
Maximum Serum Concentration (Cmax) of IdeS From day of dosing until day 14
Time-point for Maximum Serum Concentration of IdeS From day of dosing until day 14
Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of F(ab')2 Fragments From day of dosing until end of follow up on day 64
Enrollment 2
Condition
Intervention

Intervention type: Biological

Intervention name: IdeS (0.25 mg/kg)

Description: Single i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of efficacy and safety in the first 3 patients the dose may be increased in the following 3 patients to 0.5 mg/kg.

Arm group label: Treatment IdeS (0.25 mg/kg)

Other name: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes

Intervention type: Biological

Intervention name: IdeS (0.50 mg/kg)

Description: Single i.v. infusion of IdeS (0.50 mg/kg).

Arm group label: Treatment IdeS (0.50 mg/kg)

Other name: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Elisabeth Sonesson, PhD Study Director Hansa Biopharma AB
Location
facility University College London Hospitals NHS
Location Countries

United Kingdom

Verification Date

September 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Treatment IdeS (0.25 mg/kg)

Arm group type: Experimental

Description: A single 30 minutes i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of safety and efficacy in 3 patients receiving 0.25 mg/kg there will be a potential to increase the IdeS dose to 0.5 mg/kg for the remaining 3 patients.

Arm group label: Treatment IdeS (0.50 mg/kg)

Arm group type: Experimental

Description: A single 30 minutes i.v. infusion of IdeS (0.50 mg/kg).

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov