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

Phase 2

Completed

Conditions: Chronic Kidney Disease

Interventions: Biological: IdeS

Registration Number: NCT02224820

Lead Sponsor: Hansa Biopharma AB

Brief 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.

Detailed Description: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intravenous IdeS	IdeS	One or two doses of IdeS in ascending doses

Primary Outcome Measures

Name	Time	Method
Efficacy	24 hours	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.

Secondary Outcome Measures

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