Phase II Study to Evaluate Safety and Efficacy of Intravenous Immunoglobulin G Degrading Enzyme of Streptococcus Pyogenes (IdeS) in Chronic Kidney Disease

Chronic Kidney Disease Clinical Trial

Official title:

A Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous IdeS After Administration of Ascending Doses in Chronic Kidney Disease Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02224820
• Other study ID #: 13-HMedIdeS-02
• Secondary ID: 2013-005417-13
• Status: Completed
• Phase: Phase 2
• First received: August 15, 2014
• Last updated: March 17, 2015
• Start date: June 2014
• Est. completion date: February 2015

Study information

• Verified date: March 2015
• Source: Hansa Medical AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Swedish medicines products agency
• Study type: Interventional

Clinical Trial Summary

IdeS is an immunoglobulin g (IgG) cleaving enzyme. It will given to patients with donor specific antibodies to reduce the antibody load and thus enable kidney transplantation. IdeS antibody reducing efficacy and its safety will be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with chronic kidney disease and in dialysis with identified antibodies against at least two HLA antigens of which at least one is 3000 MFI or more as measured by SAB assay on at least two occasions.

Exclusion Criteria:

• Prior malignancy within 2 years excluding adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ and prostate cancer Gleason <6 and prostate-specific antigen (PSA) <10 ng/mL.

• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV

• Clinical signs of ongoing infectious disease.

• Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > New York Heart Association (NYHA) grade 3, unstable coronary disease or oxygen dependent chronic obstructive pulmonary disease (COPD)

• History of any other clinically significant disease or disorder which, in the opinion of the investigator, 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, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to IdeS (e. g streptokinase and/or staphylokinase)

• Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within 4 months of the first administration of investigational product in this study. Patients consented and screened but not dosed in previous studies are not excluded

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Biological:
• IdeS

Locations

Country	Name	City	State
Sweden	Dept. of Transplant Surgery, Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Hansa Medical AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetics (T1/2, Cmax, Tmax, AUCt) up to day 21	IdeS concentration in plasma	21 days	No
Primary	efficacy	Efficacy defined as the IdeS dosing scheme resulting in anti human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as an mean fluorescent intensity (MFI) of less than 1100 as measured in an single antigen bead (SAB) assay, within 24 hours from dosing	24 hours	No
Secondary	Safety	Adverse events, clinical laboratory tests, vital signs and ECGs	9 weeks	Yes
Secondary	Pharmacodynamics up to day 64	IgG cleavage and regeneration measured by ELISA and gel analysis	64 day	Yes
Secondary	ADA up to day 64	Anti drug antibody formation at different time points up to day 64 after dosing	64 days	Yes