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

NCT ID: NCT02854059

Last Updated: 2019-09-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2017-01-31

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.

Conditions

Purpura, Thrombotic Thrombocytopenic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

IdeS (0.25 mg/kg)

Intervention Type: BIOLOGICAL

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.

Treatment IdeS (0.50 mg/kg)

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

Group Type: EXPERIMENTAL

IdeS (0.50 mg/kg)

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: BIOLOGICAL

IdeS (0.50 mg/kg)

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

Intervention Type: BIOLOGICAL

Other Intervention Names

HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes; 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College London Hospitals

OTHER

Sponsor Role: collaborator

Hansa Biopharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisabeth Sonesson, PhD

Role: STUDY_DIRECTOR

Hansa Biopharma AB

Locations

University College London Hospitals NHS

London, Greater London, United Kingdom

Countries

United Kingdom

References

Stubbs MJ, Thomas M, Vendramin C, Sonesson E, Kjellman C, Jarnum S, Stenberg Y, Elfving C, Scully M. Administration of immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) for persistent anti-ADAMTS13 antibodies in patients with thrombotic thrombocytopenic purpura in clinical remission. Br J Haematol. 2019 Jul;186(1):137-140. doi: 10.1111/bjh.15706. Epub 2018 Nov 29. No abstract available.

Reference Type: DERIVED

PMID: 30488420 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

15-HMedIdeS-08

Identifier Type: -

Identifier Source: org_study_id