Renal Disease
Conditions
Keywords
End Stage Renal Disease, Kidney Transplant, Desensitization, Highly Sensitized, Antibodies
Brief summary
This is a single center phase I/II open label, exploratory study assessing safety and efficacy of IdeS® (Hansa Medical, Lund, Sweden) given immediately prior to kidney transplantation. We hope that IdeS® will help eliminate DSAs in HS patients who are DSA+ and flow cytometry (FCMX) crossmatch + at time of transplant. We plan to enroll a total of 20 patients. Patients will be followed for 6 months post administration of IdeS®.
Detailed description
IdeS® is an IgG-degrading enzyme of S.pyogenes that cleaves all four human subclasses of IgG with strict specificity. Alloantibodies are a major deterrent to access to and success of life-saving organ transplants. We hypothesize that the use of IdeS® pre-transplant in HS patients will represent a more robust and complete technique to eliminate DSA from the sera of HS patients. A single dose administration of IdeS® in the pre-operative period to HS patients with positive DSAs and flow cytometry crossmatches will durably eliminate circulating DSAs, allow transplantation to occur without ABMR and, in conjunction with standard desensitization therapy, result in a durable suppression of DSA levels thus eliminating the risk for ABMR.
Interventions
DRUGIdeS® (Imlifidase)
0.24mg/kg IdeS
Sponsors
Hansa Biopharma AB
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* End-stage renal disease awaiting transplantation on the UNOS list. * No known contraindications for therapy with IVIG10%/Rituximab, plasmapheresis (PLEX) or IdeS®. * Age 18-70 years at the time of screening. * Calculated PRA (CPRA)\> 50% demonstrated on 3 consecutive samples, Patient highly-HLA sensitized and a candidate for DD transplantation after desensitization at CSMC. * At transplant, patient must have donor-specific antibody/ crossmatch positive (DSA/CMX+) non-HLA identical donor. * Pre-transplant vaccination with Streptococcus pneumoniae and Nisseria meningitides * Subject/Parent/Guardian must be able to understand and provide informed consent.
Exclusion criteria
* Positivity for anti-IdeS IgE * Use of IVIG 4 weeks prior to planned IdeS® administration * Recipients of Extended Criteria Donors (ECD) or Living Donors (LD) * Lactating or pregnant females. * Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception. * HIV-positive subjects. * Subjects who test positive for HBV infection \[positive HBVsAg, HBVcAb, or HBVeAg/DNA\] or HCV infection \[positive Anti-HCV (EIA) and confirmatory HCV RIBA\]. * Subjects with active TB. * Subjects with selective IgA deficiency, those who have known anti-IgA antibodies, and those with a history of anaphylaxis or severe systemic responses to any part of the clinical trial material. * Subjects who have received or for whom multiple organ transplants are planned. * Recent recipients of any licensed or investigational live attenuated vaccine(s) within two months of the screening visit (including but not limited to any of the following: 1. Adenovirus \[Adenovirus vaccine live oral type 7\] 2. Varicella \[Varivax\] 3. Hepatitis A \[VAQTA\] 4. Rotavirus \[Rotashield\] 5. Yellow fever \[Y-F-Vax\] 6. Measles and mumps \[Measles and mumps virus vaccine live\] 7. Measles, mumps, and rubella vaccine \[M-M-R-II\] 8. Sabin oral polio vaccine 9. Rabies vaccines \[IMOVAX Rabies I.D., RabAvert\]) * A significantly abnormal general serum screening lab result defined as a WBC \< 3.0 X 103/ml, a Hgb \< 8.0 g/dL, a platelet count \< 100 X 103/ml, , an SGOT \> 3X upper limit . * Individuals deemed unable to comply with the protocol. * Subjects with active CMV or EBV infection as defined by CMV-specific serology (IgG or IgM) and confirmed by quantitative PCR with or without a compatible illness. * Subjects with a known history of previous myocardial infarction within one year of screening. * Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease. * Subjects with Protein C and Protein S deficiency * Use of investigational agents within 4 weeks of participation. * Known allergy/sensitivity to IdeS® infusions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Allograft Rejection | 6 months | Number of participants with allograft rejection will be assessed at 6 month post transplant renal biopsy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| eGFR | 6 months post transplant | eGFR based on serum creatinine will be collected 6 months post transplant. |
| Proteinuria | 6 months post transplant | Urine total protein & urine creatinine will be drawn from day 0 to day 30, and urinalysis will be collected on day 180 from transplant. |
| Number of Participants With Donor Specific Antibodies (DSA) Post-transplant | 6 months post transplant | Donor specific antibody levels will be checked at Day 180 post transplant to see if patients developed new antibodies or antibody intensity levels worsened post transplant. The DSA mean fluorescence intensity (MFI) was recorded, in comparison to the levels at transplant. This outcome measure was intended to record if any of the participants had a new DSA formation at Day 180, or if any participant had higher MFI levels of the DSA at Day 180, compared to baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IdeS® 0.24 mg/kg patients who received 0.24mg/kg (n=17) | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | IdeS® 0.24 mg/kg | — |
|---|---|---|
| Age, Customized | 41.6 years STANDARD_DEVIATION 13 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 17 participants | — |
| Sex: Female, Male Female | 9 Participants | — |
| Sex: Female, Male Male | 8 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 17 |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 5 / 17 |
Outcome results
Primary
Number of Participants With Allograft Rejection
Number of participants with allograft rejection will be assessed at 6 month post transplant renal biopsy.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IdeS® 0.24 mg/kg | Number of Participants With Allograft Rejection | 7 Participants |
Secondary
eGFR
eGFR based on serum creatinine will be collected 6 months post transplant.
Time frame: 6 months post transplant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IdeS® 0.24 mg/kg | eGFR | 66 ml/min/m2 | Standard Deviation 48 |
Secondary
Number of Participants With Donor Specific Antibodies (DSA) Post-transplant
Donor specific antibody levels will be checked at Day 180 post transplant to see if patients developed new antibodies or antibody intensity levels worsened post transplant. The DSA mean fluorescence intensity (MFI) was recorded, in comparison to the levels at transplant. This outcome measure was intended to record if any of the participants had a new DSA formation at Day 180, or if any participant had higher MFI levels of the DSA at Day 180, compared to baseline.
Time frame: 6 months post transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IdeS® 0.24 mg/kg | Number of Participants With Donor Specific Antibodies (DSA) Post-transplant | 4 Participants |
Secondary
Proteinuria
Urine total protein & urine creatinine will be drawn from day 0 to day 30, and urinalysis will be collected on day 180 from transplant.
Time frame: 6 months post transplant
Population: This outcome was not assessed