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

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 66 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:

    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

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: IdeS®
Twenty patients will receive 0.24mg/kg (n=20)
Drug: IdeS® (Imlifidase)
0.24mg/kg IdeS
Other Names:
  • IgG endopeptidase

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cedars-Sinai Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hansa Biopharma AB

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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 16, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 10, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 10, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 22, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 27, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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