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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02854059
Recruitment Status : Terminated (Sponsor review of initial results demonstrates a non-favourable risk benefit)
First Posted : August 3, 2016
Results First Posted : September 13, 2019
Last Update Posted : September 13, 2019
Sponsor:
Collaborator:
University College London Hospitals
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Purpura, Thrombotic Thrombocytopenic Biological: IdeS (0.25 mg/kg) Biological: IdeS (0.50 mg/kg) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017


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.
Biological: IdeS (0.25 mg/kg)
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 Name: 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).
Biological: IdeS (0.50 mg/kg)
Single i.v. infusion of IdeS (0.50 mg/kg).
Other Name: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02854059


Locations
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United Kingdom
University College London Hospitals NHS
London, Greater London, United Kingdom, NW1 2PG
Sponsors and Collaborators
Hansa Biopharma AB
University College London Hospitals
Investigators
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Study Director: Elisabeth Sonesson, PhD Hansa Biopharma AB
  Study Documents (Full-Text)

Documents provided by Hansa Biopharma AB:
Study Protocol  [PDF] June 21, 2016
Statistical Analysis Plan  [PDF] September 22, 2017


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Responsible Party: Hansa Biopharma AB
ClinicalTrials.gov Identifier: NCT02854059    
Other Study ID Numbers: 15-HMedIdeS-08
First Posted: August 3, 2016    Key Record Dates
Results First Posted: September 13, 2019
Last Update Posted: September 13, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.
Keywords provided by Hansa Biopharma AB:
Asymptomatic antibody-mediated TTP
Additional relevant MeSH terms:
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Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs