- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02854059
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Greater London
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London, Greater London, United Kingdom, NW1 2PG
- University College London Hospitals NHS
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
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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:
|
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.
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From day of dosing until end of follow up on day 64
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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.
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From day of dosing until end of follow up on day 64
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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.
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From day of dosing until end of follow up on day 64
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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.
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From day of dosing until end of follow up on day 64
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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
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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.
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From day of dosing until end of follow up on day 64
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Maximum Serum Concentration (Cmax) of IdeS
Time Frame: From day of dosing until day 14
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The concentration of IdeS in serum was measured to identify the pharmacokinetic parameter Cmax of IdeS in TTP patients.
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From day of dosing until day 14
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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.
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From day of dosing until day 14
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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
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Elisabeth Sonesson, PhD, Hansa Biopharma AB
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 15-HMedIdeS-08
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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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