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

NCT02854059 | Terminated Phase 2 Results DMC

• 1 other identifier: 15-HMedIdeS-08
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Purpura, Thrombotic Thrombocytopenic

Keywords

Asymptomatic antibody-mediated TTP

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events

  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 Outcomes (8)

• Number of Patients With Change From Baseline in ADAMTS13 Activity

  From day of dosing until end of follow up on day 64

• Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels

  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

  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

  From day of dosing until end of follow up on day 64

• Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies

  From day of dosing until end of follow up on day 64

Study Arms (2)

Treatment IdeS (0.25 mg/kg)

EXPERIMENTAL

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)

Treatment IdeS (0.50 mg/kg)

EXPERIMENTAL

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

Biological: IdeS (0.50 mg/kg)

Interventions

IdeS (0.25 mg/kg) 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.

Also known as: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes

Treatment IdeS (0.25 mg/kg)

IdeS (0.50 mg/kg) BIOLOGICAL

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

Also known as: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes

Treatment IdeS (0.50 mg/kg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hansa Biopharma AB: lead
• University College London Hospitals: collaborator

Study Sites (1)

University College London Hospitals NHS

London, Greater London, NW1 2PG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30488420 DERIVED

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Limitations and Caveats

Early termination leading to small number of subjects analyzed.

Results Point of Contact

• Title: Elisabeth Sonesson (Director Clinical Operations)
• Organization: Hansa Biopharma AB

elisabeth.sonesson@hansabiopharma.com

+46 (0)708 54 86 46

Study Officials

• Elisabeth Sonesson, PhD

  Hansa Biopharma AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 3, 2016
• Study Start: September 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: September 13, 2019
• Results First Posted: September 13, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)