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

Phase 2

Terminated

• Conditions: Purpura, Thrombotic Thrombocytopenic
• Interventions: Biological: IdeS (0.25 mg/kg); Biological: IdeS (0.50 mg/kg)

• Registration Number: NCT02854059
• Lead Sponsor: 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.

Study Timeline

• Study First Submitted: 2016-07-27
• Study First Submitted QC: 2016-07-29
• Study First Posted: 2016-08-03
• Study Start: 2016-09
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Results First Submitted: 2019-06-10
• Status Verified: 2019-09
• Results First Submitted QC: 2019-09-12
• Last Update Submitted: 2019-09-12
• Results First Posted: 2019-09-13
• Last Update Posted: 2019-09-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment IdeS (0.25 mg/kg)	IdeS (0.25 mg/kg)	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.
Treatment IdeS (0.50 mg/kg)	IdeS (0.50 mg/kg)	A single 30 minutes i.v. infusion of IdeS (0.50 mg/kg).

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events	From dosing until end of follow up on day 64	Data on AEs were obtained if spontaneously reported by the patient, if reported in response to an open question from the study personnel or if revealed by observation.; A treatment emergent AE (TEAE) is defined as any AE occurring after administration of the IMP and within the time of the residual drug effect period (i.e. 30 days after IMP administration).; AEs reported in ClinicalTrials.gov include TEAEs and post-treatment AEs, i.e. all AEs occurring after administration of IdeS until end of study.; Please refer to Adverse Event section for details on reported AEs

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Change From Baseline in ADAMTS13 Activity	From day of dosing until end of follow up on day 64	ADAMTS13 is an enzyme which is inhibited in patients with TTP. The efficacy of IdeS on ADAMTS13 activity was measured througout the study as change from baseline.
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	IdeS cleaves IgG molecules. The concentration of uncleaved IgG in the patient's serum was measured throughout the study to determine change from baseline following IdeS administration.
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	The ADAMTS13 activity in TTP patients is decreased. The efficacy of IdeS on ADAMTS13 activity was assessed throughout the study to identify the time-point of return to normal levels.
Maximum Serum Concentration (Cmax) of IdeS	From day of dosing until day 14	The concentration of IdeS in serum was measured to identify the pharmacokinetic parameter Cmax of IdeS in TTP patients.
Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels	From day of dosing until end of follow up on day 64	The efficacy of IdeS on ADAMTS13 antibody cleaving was measured througout the study as change from baseline in ADAMTS13 antibody concentration.
Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies	From day of dosing until end of follow up on day 64	Most humans have been infected with S. pyogenes which is the origin of IdeS. It was therefore expected that patients in this study might have antibodies against IdeS before being exposed to IdeS in the study. The concentration of ant-IdeS antibodies was measured before dosing and throughout the study.
Time-point for Maximum Serum Concentration of IdeS	From day of dosing until day 14	The concentration of IdeS in serum was measured to identify the pharmacokinetic parameter Tmax of IdeS in TTP patients. Tmax refers to the time-point when the serum concentration of IdeS reaches maximum.
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	The efficacy of IdeS can be measured as change from baseline in F(ab')2 fragments (i.e. the antigen binding fragment of IgG).

Trial Locations

Locations (1)

University College London Hospitals NHS; 🇬🇧 London, Greater London, United Kingdom