What side effects are associated with this type of intervention?

Common treatments for kidney transplantation, such as immunosuppressive therapies and high-dose immunoglobulins, can have several side effects. Immunosuppressive agents like glucocorticoids, cyclophosphamide, and mycophenolate mofetil can lead to increased risk of infections, gastrointestinal disturbances, and potential bone marrow suppression. High-dose immunoglobulins, used to modulate antibody levels, may cause infusion-related reactions, headaches, and in rare cases, thromboembolic events. These treatments aim to reduce the risk of organ rejection but require careful monitoring to manage these potential side effects.

What prior FDA approvals exist?

FDA-approved treatments for kidney transplantation include various immunosuppressive agents aimed at preventing organ rejection. These include calcineurin inhibitors like tacrolimus and cyclosporine, antiproliferative agents such as mycophenolate mofetil, and mTOR inhibitors like sirolimus. Additionally, monoclonal antibodies such as basiliximab and alemtuzumab are used for induction therapy. While Imlifidase is an IgG-cleaving enzyme used for desensitization in highly sensitized patients, similar desensitization strategies include the use of intravenous immunoglobulin (IVIG) and plasmapheresis to reduce antibody levels and improve transplant outcomes.

What other types of research exist?

Promising alternatives to Imlifidase for kidney transplantation patients include CTLA4-Ig (developed by Bristol-Myers Squibb) and other immunomodulatory agents like rituximab and mycophenolate mofetil. These agents are being explored for their potential to manage antibody levels and improve transplant outcomes.

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Enzyme

Imlifidase Desensitization for Kidney Transplant Patients (ConfIdeS Trial)

Phase 3

Waitlist Available

Research Sponsored by Hansa Biopharma AB

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Chronic kidney disease (CKD) stage 5, highly sensitized as evaluated by standard selection criteria, and active on the OPTN waiting list for a DD kidney transplant

Male or female age 18-70 years at the time of screening

Must not have

History of a proven hypercoagulable condition

Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure ≥grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent chronic obstructive pulmonary disease (COPD)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from signing informed consent to 12 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing imlifidase, a treatment that removes harmful antibodies, in highly sensitized kidney transplant patients. These patients are at high risk of rejecting a new kidney due to their antibodies. Imlifidase helps clear these antibodies to prevent rejection and holds promise to be a game-changer for sensitized patients in need of lifesaving organ transplants.

Who is the study for?

This trial is for adults aged 18-70 with chronic kidney disease stage 5, highly sensitized (cPRA ≥99.9%), and on the waitlist for a deceased donor kidney transplant. They must be able to follow the study plan and join a 4-year extension trial. Pregnant or breastfeeding individuals, those with certain infections like HIV/HBV/HCV, active tuberculosis, or severe conditions that prevent transplantation are excluded.

What is being tested?

The study tests if imlifidase used before a kidney transplant can improve renal function in patients who have high antibody levels against potential donors. It's compared to standard care including anti-CD20 antibodies and other treatments like PLEX and IVIg in an open-label, randomized Phase 3 trial over one year.

What are the potential side effects?

Possible side effects include reactions related to immune system suppression such as increased risk of infections, infusion-related reactions from medications given through veins, allergic responses to drugs used during desensitization processes like Imlifidase or Eculizumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have severe kidney disease, am highly sensitized, and waiting for a donor kidney.

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I am between 18 and 70 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a confirmed condition that causes excessive blood clotting.

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I do not have severe heart issues, unstable heart disease, or severe COPD needing oxygen.

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I received a high dose IVIg treatment within the last 28 days.

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I have or had TTP, or it runs in my family.

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I show signs of CMV or EBV infection.

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I show signs of hepatitis B or C infection.

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I have active tuberculosis.

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I have been treated with imlifidase before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from signing informed consent to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from signing informed consent to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from signing informed consent to 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Mean estimated glomerular filtration rate (eGFR) at 12 months

Secondary study objectives

Patient survival at 12 months

Other study objectives

Anti-drug antibodies (ADA)

Antibody-mediated rejection (AMR) frequency

Cell-mediated rejection (CMR) frequency

+18 more

Side effects data

From 2020 Phase 2 trial • 15 Patients • NCT03157037

40%

Anaemia

27%

Nausea

20%

Hypertension

13%

Vomiting

13%

Urinary tract infection

13%

Hyperglycaemia

13%

Diarrhoea

13%

Tinnitus

13%

Leukopenia

Diarrhea

Back pain

Decreased appetite

Haematuria

Pyrexia

Viral infection

Pneumonia

Dehydration

Muscle spasms

Sinus pain

Cardiac failure

Hypogammaglobulinaemia

Blood iron decreased

Pneumonia klebsiella

Foreign body sensation in eyes

Fatigue

Herpes zoster

Hyperphosphataemia

Thrombophlebitis

Thrombocytopenia

Cryoglobulinaemia

Clostridium difficile infection

Red blood cell count decreased

Hypoglycaemia

Steroid diabetes

Rash erythematous

Urticaria

Arthralgia

Ecchymosis

Dyspnoea

Hyperhidrosis

Gastroenteritis

Pelvic venous thrombosis

Mouth ulceration

Rectal haemorrhage

Influenza like illness

Nasopharyngitis

Cystitis

Humerus fracture

Fall

Vision blurred

Chest discomfort

Clostridium difficile colitis

Limb injury

Anti-glomerular basement membrane antibody positive

Borrelia test positive

Hyperkalaemia

Tendon pain

Post herpetic neuralgia

Menorrhagia

Chronic obstructive pulmonary disease

Dermatitis allergic

Lipoma

Deep vein thrombosis

Cognitive disorder

Dizziness

Headache

Bronchial obstruction

Lymphopenia

100%

80%

60%

40%

20%

Study treatment Arm

Safety Analysis Set

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: ImlifidaseExperimental Treatment1 Intervention

Imlifidase, is provided as a freeze-dried powder for concentrate for solution for infusion, 11 mg per vial. After reconstitution with sterile water for injection, the concentrate contains 10 mg/mL imlifidase. Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes generally 24 hours prior to transplantation. A second dose of 0.25 mg/kg may be given if the first imlifidase dose is considered not to have had sufficient effect.

Group II: Best available treatmentExperimental Treatment5 Interventions

Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Anti-CD20 antibodies

2022

Completed Phase 4

~30

Eculizumab

2009

Completed Phase 4

~1200

Imlifidase

2017

Completed Phase 2

~80

PLEX

2007

Completed Phase 4

~90

IVIg

2013

Completed Phase 2

~140

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for kidney transplantation, such as Imlifidase, plasmapheresis, IVIG, and monoclonal antibodies like rituximab, work by reducing antibody levels in the blood. Imlifidase is an IgG-cleaving enzyme that directly breaks down antibodies, while plasmapheresis physically removes them, IVIG neutralizes them, and rituximab depletes the B cells that produce them. These mechanisms are crucial for highly sensitized patients who have pre-existing antibodies that can attack the transplanted kidney, as reducing antibody levels helps prevent acute rejection and improves the chances of transplant success and long-term kidney function.

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