Chronic Kidney Disease
Conditions
Keywords
transplantation, sensitised patients, HLA-antibodies
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).
Interventions
BIOLOGICALIdeS
Doses are administered in ascending doses
Sponsors
Hansa Biopharma AB
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Safety | 9 weeks | Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs) |
| Pharmacodynamics | Up to day 64 | IgG cleavage and regeneration measured by ELISA |
| Immunogenicity | Up to 64 days | Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period |
| Pharmacokinetics | Up to 21 days | IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded. |
Countries
Sweden
Participant flow
Recruitment details
The study was performed at a medical clinic, the Department of Transplantat Surgery, Uppsala, SE between 10 Jun 2014 and 13 Feb 2015. The patients had chronic kidney disease, were in dialysis and on the waiting list for transplantation. (Transplantation was not part of the protocol).
Pre-assignment details
In total, 10 patients were assessed for eligibility. One patient declined to participate and one patient was not available for recieving information about the study. Eight patients were enrolled and started treatment.
Participants by arm
| Arm | Count |
|---|---|
| Intravenous IdeS One or two doses of IdeS in ascending doses
IdeS | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Intravenous IdeS |
|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 11.9 |
| BMI | 25.1 kg/mg^2 STANDARD_DEVIATION 4.5 |
| Gender Female | 5 Participants |
| Gender Male | 3 Participants |
| Height | 172.3 cm STANDARD_DEVIATION 9.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Weight (kg) | 74.5 kg STANDARD_DEVIATION 14.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 4 / 8 |
Outcome results
Primary
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.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous IdeS | Efficacy | 372 MFI |
Secondary
Immunogenicity
Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period
Time frame: Up to 64 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravenous IdeS | Immunogenicity | 8 participants |
Secondary
Pharmacodynamics
IgG cleavage and regeneration measured by ELISA
Time frame: Up to day 64
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous IdeS | Pharmacodynamics | 30 µg/mL | Standard Deviation 3 |
Secondary
Pharmacokinetics
IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.
Time frame: Up to 21 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous IdeS | Pharmacokinetics | 5 h |
Secondary
Safety
Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)
Time frame: 9 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravenous IdeS | Safety | 76 Adverse events |