- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02426684
Ides in Highly Sensitized (HS) Patients Awaiting Kidney Transplantation
April 21, 2022 updated by: Stanley Jordan, MD, Cedars-Sinai Medical Center
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.
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®.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 68 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IdeS®
Twenty patients will receive 0.24mg/kg (n=20)
|
0.24mg/kg IdeS
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Allograft Rejection
Time Frame: 6 months
|
Number of participants with allograft rejection will be assessed at 6 month post transplant renal biopsy.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
eGFR
Time Frame: 6 months post transplant
|
eGFR based on serum creatinine will be collected 6 months post transplant.
|
6 months post transplant
|
Proteinuria
Time Frame: 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.
|
6 months post transplant
|
Number of Participants With Donor Specific Antibodies (DSA) Post-transplant
Time Frame: 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.
|
6 months post transplant
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 16, 2015
Primary Completion (Actual)
November 10, 2017
Study Completion (Actual)
November 10, 2017
Study Registration Dates
First Submitted
April 22, 2015
First Submitted That Met QC Criteria
April 24, 2015
First Posted (Estimate)
April 27, 2015
Study Record Updates
Last Update Posted (Actual)
May 16, 2022
Last Update Submitted That Met QC Criteria
April 21, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IdeSCSMC
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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