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

September 12, 2019 updated by: Hansa Biopharma AB

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Greater London
      • London, Greater London, United Kingdom, NW1 2PG
        • University College London Hospitals NHS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment 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.
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.
Other Names:
  • HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes
Experimental: Treatment IdeS (0.50 mg/kg)
A single 30 minutes i.v. infusion of IdeS (0.50 mg/kg).
Single i.v. infusion of IdeS (0.50 mg/kg).
Other Names:
  • HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events
Time Frame: 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

From dosing until end of follow up on day 64

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Change From Baseline in ADAMTS13 Activity
Time Frame: 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.
From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
From day of dosing until end of follow up on day 64
Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies
Time Frame: 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.
From day of dosing until end of follow up on day 64
Maximum Serum Concentration (Cmax) of IdeS
Time Frame: 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.
From day of dosing until day 14
Time-point for Maximum Serum Concentration of IdeS
Time Frame: 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.
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
Time Frame: 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).
From day of dosing until end of follow up on day 64

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Elisabeth Sonesson, PhD, Hansa Biopharma AB

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

July 27, 2016

First Submitted That Met QC Criteria

July 29, 2016

First Posted (Estimate)

August 3, 2016

Study Record Updates

Last Update Posted (Actual)

September 13, 2019

Last Update Submitted That Met QC Criteria

September 12, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

An internal monitoring committee (IMC) at the sponsor will review available safety and tolerability data after 3 patients have received a dose of 0.25 mg/kg before proceeding to the next dose (0.5 mg/kg). Safety data collected up to and including day 14 will be evaluated.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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