Phase II Study, Evaluation of Safety and Efficacy of IdeS in Chronic Kidney Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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Study 13-HMedIdeS-02 (EudraCT no. 2013-005417-13) is a single centre, single arm, dose finding, Phase II study in sensitized CKD patients assessing safety, tolerability, pharmacokinetics (PK) and efficacy of HMED-IdeS without intent to transplantation. However, patients are not removed from the transplant waitlist during the study. Included patients has a panel reactive antibody [PRA] >70% (n=7).

Official Title
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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

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Biological: IdeS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous IdeS<br>One or two doses of IdeS in ascending doses | Biological: IdeS<br>* Doses are administered in ascending doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Efficacy was defined as the IdeS dosing scheme in the majority of the patients resulting in human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as mean fluorescent intensity (MFI) of less than 1100, within 24 hours from dosing. MFI was determined by single antigen bead (SAB) assay and detection of complement fixating ability (CIq Screen) in serum. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs) | 9 weeks | 
| Pharmacodynamics | IgG cleavage and regeneration measured by ELISA | Up to day 64 | 
| Immunogenicity | Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period | Up to 64 days | 
| Pharmacokinetics | IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded. | Up to 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transplantation, sensitised patients, HLA-antibodies