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Kidney Failure, ChronicPhase 2HighdesNCT02790437

A Phase II Study to Evaluate the Efficacy of IdeS to Desensitize Transplant Patients With a Positive Crossmatch Test

A Phase 2 study testing IdeS and Kidney transplantation in people with Kidney Failure, Chronic, run by Hansa Biopharma AB at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the effectiveness of the study drug IdeS in patients who are on the waiting list for kidney transplant and have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Kidney Failure, Chronic
What is being tested?
IdeS and Kidney transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
5 sitesin 3 countries
Study dates
Jun 2016to 3 Jul 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients on the kidney transplant waitlist who have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. The breadth and strength of sensitization will predict an extremely low likelihood of successful desensitization or kidney paired donation.
  • Patients with a live or deceased donor with a positive crossmatch test.

Who cannot join

  • Previous treatment with IdeS
  • Previous high dose IVIg treatment (2 g/kg BW) within 28 days prior to IdeS treatment
  • Lactating or pregnant females
  • Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception
  • HIV-positive patients
  • Patients with clinical signs of HBV or HCV infection
Show all 15Show fewer
  • Patients with active tuberculosis
  • A significantly abnormal general serum screening lab result according to the investigator's judgement. Hgb cannot be < 6.0 g/dL
  • Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
  • Individuals deemed unable to comply with the protocol
  • Patients with clinical signs of CMV or EBV infection
  • Patients with a history of major thrombotic events, patients with active peripheral vascular disease or patients with proven hypercoagulable conditions
  • Patients should not have received investigational drugs within 4 half-lives (or similar)
  • Known allergy/sensitivity to IdeS infusions
  • Patients who have a live donor and test positive for ImmunoCap anti-IdeS IgE

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

United States3 sites

  • The Johns Hopkins Hospital

    Baltimore, Maryland, 21205

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • New York University School of Medicine

    New York, New York, 10016

Other trials in United States

France1 site

  • Necker Hospital

    Paris, 75743

Other trials in France

Sweden1 site

  • Uppsala University Hospital

    Uppsala, 75185

Other trials in Sweden

About this study

Official title: A Phase II Study to Evaluate the Efficacy of IdeS (IgG Endopeptidase) to Desensitize Transplant Patients With a Positive Crossmatch Test

The purpose of this study is to evaluate the effectiveness of the study drug IdeS in patients who are on the waiting list for kidney transplant and have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. At study entry, the patients will have an available deceased or live donor with a positive crossmatch test. The study will assess IdeS efficacy and safety in removing Donor Specific Antibodies (DSAs) and thereby convert a positive crossmatch test to negative.

Read the detailed description

The study will assess the IdeS efficacy in creating a negative crossmatch test (XM) in patients who exhibit donor specific antibodies (DSA) and have a positive crossmatch test to their available live or deceased donors. The first 3 patients in this study will receive a kidney from a deceased donor. The study will primarily examine the efficacy of IdeS in creating a negative XM. The first 3 patients will receive one dose of 0.25 mg/kg BW IdeS on study day 0. If it is considered safe and negative crossmatch test is not achieved after the first dose, an additional IdeS infusion can be given within 2 days of the first infusion. The dose schedule may be increased to 0.5 mg/kg BW given once or twice after the first 3 patients have been tested. The decision to escalate the dose will be done after evaluation of safety and efficacy.

Being tested
IdeS, Kidney transplantation
Medical subject headings
Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IdeSDrug

    Also called IgG endopeptidase

    One dose of 0.25 mg/kg BW IdeS on study day 0. If negative crossmatch is not achieved, a second dose can be given within 2 days of the first infusion.

  • Kidney transplantationProcedure or surgery

    Performed following IdeS treatment

Study groups in NCT02790437
Study groupRoleWhat they receive
Treatment IdeSExperimentalIdeS intravenous infusion
Receives: Drug: IdeS; Procedure: Kidney transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Crossmatch Conversion (Positive to Negative)

    IdeS ability to create a negative crossmatch (XM) test in patients who before treatment exhibit Donor Specific Antibodies (DSAs) and have a positive XM test to their available live or deceased donor kidney.

    XM was assessed using both FACS and CDC XM tests. FACS XM is a multi-staining procedure where the recipient's serum is used to stain donor cells to identify presence of DSAs in recipient's serum. T- and B-cells are identified using conjugated antibodies against CD3 and CD19. DSAs are identified using a conjugated anti-human antibody. CDC XM evaluates the cytotoxic capacity of the DSAs. The recipient's serum is mixed with donor cells prior to addition of complement. Fluorescent dyes are added and the live/dead cells (%) is scored using a fluorescent microscope. CDC XM amplified with anti-human globulin is not compatible with imlifidase and should not be used.

    The endpoint was met if at least one XM test was positive pre-dose and the last test within 24 h was negative.

    Measured: Within 24 hours of IdeS dosing

Secondary outcomes (14)

  1. Number of Patients With Donor Specific Antibodies With an MFI Value >3000

    Donor specific antibodies (DSA) level at different time points within 180 days after administration of IdeS.

    DSA levels were measured using the single antigen beads (SAB) anti-HLA assay. The levels were determined as mean fluorescence intensity (MFI).

    Positive DSA (i.e. HLA antibodies) were defined as having a MFI value >3000.

    Measured: Within 180 days after administration of IdeS.

  2. Time to Create a Negative CDC Crossmatch Test

    Time to create a negative CDC crossmatch (XM) was defined as the first timepoint all CDC XM results were negative.

    Measured: 2h, 6h, 24h after administration of IdeS.

  3. Time to Create a Negative FACS Crossmatch Test

    Time to create a negative FACS crossmatch (XM) was defined as the first timepoint all FACS XM results were negative.

    Measured: 2h, 6h, and 24h after administration of IdeS

  4. Kidney Function After IdeS Treatment Assessed by eGFR

    Estimated glomerular filtration rate (eGFR) was calculated as described by the MDRD equation. eGFR is a measure of kidney function.

    eGFR for a kidney with normal function is 90 mL/min/1.72m2. Kidney disease is characterised by a decreased eGFR value.

    Measured: Within 180 days after administration of IdeS

  5. Serum IgG Concentration After Administration of IdeS

    The patient's immunoglobulin G (IgG) is cleaved by IdeS in two steps. The first cut separates one of the heavy chains from the Fc part, generating so called single-cleaved IgG (scIgG), and the second cut separates the other heavy chain from the Fc part, thus generating one F(ab')2 fragment and one Fc fragment. The IgG concentration measured for this outcome is the sum of intact and scIgG because the assay used cannot discriminate between the two. A decrease in IgG concentration therefore represents complete cleavage of the IgG molecules to Fc and F(ab')2 fragments.

    Please note that intravenous IgG (IVIg) was administered Day 7.

    Measured: Within 180 days after administration of IdeS.

  6. Pharmacokinetics - Cmax (First Dose)

    Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)

    Measured: Pre-dose to Day 14 after administration of IdeS.

  7. Pharmacokinetics - Cmax (Second Dose)

    Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)

    Measured: Pre-dose until Day 14 after administration of IdeS

  8. Pharmacokinetics - Tmax (First Dose)

    Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)

    Measured: Pre-dose to Day 14 after administration of IdeS

  9. Pharmacokinetics - Tmax (Second Dose)

    Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)

    Measured: Pre-dose to Day 14 after administration of IdeS

  10. Pharmacokinetics - AUC

    AUC = Area under the plasma concentration versus time curve (Non-compartmental PK analysis)

    Measured: Pre-dose to Day 14 after administration of IdeS.

  11. Pharmacokinetics - t1/2

    Alpha-t1/2 = Half-life during distribution phase Beta-t1/2 = Half-life during elimination phase Non-compartmental PK analysis

    Measured: Pre-dose to Day 14 after administration of IdeS.

  12. Pharmacokinetics - CL

    CL = Clearance Non compartmental PK analysis

    Measured: Pre-dose to Day 14

  13. Pharmacokinetics - Vss

    Vss = Volume of distribution at steady state Non compartmental PK analysis

    Measured: Pre-dose to Day 14 after administration of IdeS

  14. Pharmacokinetics - Vz

    Vz = Volume of distribution during the elimination phase Non compartmental PK analysis

    Measured: Pre-dose to Day 14 after administration of IdeS.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion12 Dec 2017
  4. Study completion3 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02790437
Sponsor's protocol ID
15-HMedIdeS-06
Acronym
Highdes
Status last verified
Apr 2021
First submitted
30 May 2016
Last updated
20 May 2021
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Lorant T, Lonze BE, Montgomery RA, Desai NM, Legendre C, Lundgren T, von Zur-Muhlen B, Vo AA, Sjoholm K, Runstrom A, Tollemar J, Jordan SC. Five Years Follow-up of Imlifidase Desensitized Kidney Transplant Recipients. Transpl Int. 2025 Nov 27;38:15425. doi: 10.3389/ti.2025.15425. eCollection 2025.

    PubMed 41394519

  • Jaffe IS, Runstrom A, Tatapudi VS, Weldon EP, Deterville CL, Dieter RA, Montgomery RA, Lonze BE, Mangiola M. Clinical Outcomes and Donor-specific Antibody Rebound 5 y After Kidney Transplant Enabled by Imlifidase Desensitization. Transplant Direct. 2025 Jan 9;11(2):e1752. doi: 10.1097/TXD.0000000000001752. eCollection 2025 Feb.

    PubMed 39802198

  • Kjellman C, Maldonado AQ, Sjoholm K, Lonze BE, Montgomery RA, Runstrom A, Lorant T, Desai NM, Legendre C, Lundgren T, von Zur Muhlen B, Vo AA, Olsson H, Jordan SC. Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients. Am J Transplant. 2021 Dec;21(12):3907-3918. doi: 10.1111/ajt.16754. Epub 2021 Jul 19.

    PubMed 34236770

  • Jordan SC, Legendre C, Desai NM, Lorant T, Bengtsson M, Lonze BE, Vo AA, Runstrom A, Laxmyr L, Sjoholm K, Schiott A, Sonesson E, Wood K, Winstedt L, Kjellman C, Montgomery RA. Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes). Transplantation. 2021 Aug 1;105(8):1808-1817. doi: 10.1097/TP.0000000000003496.

    PubMed 33093408

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IdeS and Kidney transplantation in people with Kidney Failure, Chronic, run by Hansa Biopharma AB at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, France, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Crossmatch Conversion (Positive to Negative) (time frame: Within 24 hours of IdeS dosing). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02790437, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2021.

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