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Ides in Highly Sensitized (HS) Patients Awaiting Kidney Transplantation

Primary Purpose

Renal Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IdeS® (Imlifidase)
Sponsored by
Cedars-Sinai Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Disease focused on measuring End Stage Renal Disease, Kidney Transplant, Desensitization, Highly Sensitized, Antibodies

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cedars-Sinai Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IdeS®

Arm Description

Twenty patients will receive 0.24mg/kg (n=20)

Outcomes

Primary Outcome Measures

Number of Participants With Allograft Rejection
Number of participants with allograft rejection will be assessed at 6 month post transplant renal biopsy.

Secondary Outcome Measures

eGFR
eGFR based on serum creatinine will be collected 6 months post transplant.
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.
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.

Full Information

First Posted
April 22, 2015
Last Updated
April 21, 2022
Sponsor
Cedars-Sinai Medical Center
Collaborators
Hansa Biopharma AB
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1. Study Identification

Unique Protocol Identification Number
NCT02426684
Brief Title
Ides in Highly Sensitized (HS) Patients Awaiting Kidney Transplantation
Official Title
A Phase I/II Trial to Evaluate the Safety and Tolerability of Ides® (IgG Endopeptidase) to Eliminate Donor Specific HLA Antibodies (DSAs) and Prevent Antibody-Mediated Rejection Post-Transplant in Highly-HLA Sensitized Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 16, 2015 (Actual)
Primary Completion Date
November 10, 2017 (Actual)
Study Completion Date
November 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cedars-Sinai Medical Center
Collaborators
Hansa Biopharma AB

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Disease
Keywords
End Stage Renal Disease, Kidney Transplant, Desensitization, Highly Sensitized, Antibodies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IdeS®
Arm Type
Experimental
Arm Description
Twenty patients will receive 0.24mg/kg (n=20)
Intervention Type
Drug
Intervention Name(s)
IdeS® (Imlifidase)
Other Intervention Name(s)
IgG endopeptidase
Intervention Description
0.24mg/kg IdeS
Primary Outcome Measure Information:
Title
Number of Participants With Allograft Rejection
Description
Number of participants with allograft rejection will be assessed at 6 month post transplant renal biopsy.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
eGFR
Description
eGFR based on serum creatinine will be collected 6 months post transplant.
Time Frame
6 months post transplant
Title
Proteinuria
Description
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
Title
Number of Participants With Donor Specific Antibodies (DSA) Post-transplant
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Adenovirus [Adenovirus vaccine live oral type 7] Varicella [Varivax] Hepatitis A [VAQTA] Rotavirus [Rotashield] Yellow fever [Y-F-Vax] Measles and mumps [Measles and mumps virus vaccine live] Measles, mumps, and rubella vaccine [M-M-R-II] Sabin oral polio vaccine 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stanley C Jordan, MD
Organizational Affiliation
Cedars-Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22248585
Citation
von Pawel-Rammingen U. Streptococcal IdeS and its impact on immune response and inflammation. J Innate Immun. 2012;4(2):132-40. doi: 10.1159/000332940. Epub 2012 Jan 17.
Results Reference
background
PubMed Identifier
28767349
Citation
Jordan SC, Lorant T, Choi J, Kjellman C, Winstedt L, Bengtsson M, Zhang X, Eich T, Toyoda M, Eriksson BM, Ge S, Peng A, Jarnum S, Wood KJ, Lundgren T, Wennberg L, Backman L, Larsson E, Villicana R, Kahwaji J, Louie S, Kang A, Haas M, Nast C, Vo A, Tufveson G. IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation. N Engl J Med. 2017 Aug 3;377(5):442-453. doi: 10.1056/NEJMoa1612567. Erratum In: N Engl J Med. 2017 Oct 26;377(17 ):1700.
Results Reference
derived

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Ides in Highly Sensitized (HS) Patients Awaiting Kidney Transplantation

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