Felzartamab in Late Antibody-Mediated Rejection

  • STATUS
    Recruiting
  • End date
    Dec 17, 2024
  • participants needed
    20
  • sponsor
    Farsad Eskandary
Updated on 4 October 2022

Summary

This prospective trial will assess the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and efficacy of the fully human CD38 monoclonal antibody felzartamab in kidney transplant recipients with late active or chronic-active ABMR. The study is designed as a randomized, controlled, double-blind pilot phase 2 trial. Participants will be randomized to receive either felzartamab or placebo for a period of six months, and then followed for another six months. After six and twelve months, study participants will be subjected to follow-up allograft biopsies.

Description

This prospective bi-center study (University of Vienna, Charité Universitätsmedizin Berlin; Sponsor: Medical University of Vienna, Vienna, Austria; Funder: MorphoSys AG, Planegg, Germany) is an investigator-driven pilot trial designed to assess the safety&tolerability (primary endpoint), pharmacokinetics, immunogenicity, pharmacodynamics and efficacy (preliminary assessment) of the fully human CD38 monoclonal antibody felzartamab in kidney transplant recipients diagnosed with late active or chronic-active antibody-mediated rejection (ABMR) after kidney transplantation.

Adult renal allograft recipients with anti-HLA donor-specific antibodies (DSA) and biopsy-proven ABMR (Banff 2019 classification) ≥180 days post-transplantation will be identified and recruited at the kidney transplantation outpatient services of the two center sites.

The primary endpoint will be safety and tolerability. Participants will be randomized to receive either felzartamab (intravenous administration) or placebo (1:1 randomization stratified by study site and according to ABMR categories) for a period of 6 months (administration of felzartamab/placebo at day 0, 7, 14, 21, and thereafter in 4-weekly intervals. After six (week 24) and twelve months (week 52), study participants will be subjected to follow-up allograft biopsies.

Primary goals of the trial are to assess the safety, pharmacokinetics and pharmacodynamics (peripheral blood plasma cell and natural killer cell depletion) of a 6-month course of treatment over a period of 12 months. The trial will in addition provide first data on efficacy (progression/activity of rejection, blood biomarkers) and potential associations of treatment with parameters reflecting clinical progression of allograft dysfunction, including the course of estimated glomerular filtration rate.

Details
Condition Antibody-mediated Rejection
Treatment Placebo, Felzartamab
Clinical Study IdentifierNCT05021484
SponsorFarsad Eskandary
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Voluntary written informed consent
Age >18 years (maximum: 80 years)
Functioning living or deceased donor allograft after ≥180 days post-transplantation
eGFR ≥20 ml/min/1.73 m2 (CKD-EPI formula)
HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA)
Active or chronic/active ABMR (±C4d in PTC) according to the Banff 2019 classification
Molecular ABMR score (MMDx) ≥0.2

Exclusion Criteria

Patients actively participating in another clinical trial
Age ≤18 years
Female subject is pregnant or lactating or not on adequate contraceptive therapy
ABO-incompatible transplant
Index biopsy results
T-cell-mediated rejection classified Banff grade ≥I
De novo or recurrent severe thrombotic microangiopathy
Polyoma virus nephropathy
De novo or recurrent glomerulonephritis
Acute rejection treatment ≤3 month before screening
Previous treatment with other CD38 monoclonal antibodies (e.g. daratumumab)
Previous treatment with other immunomodulatory monoclonal/polyclonal antibodies (e.g. CD20 Ab rituximab, IL-6/IL-6R Ab) ≤3 months before study treatment
Total bilirubin >2×the upper limit of normal [ULN], alanine transaminase and aspartate aminotransferase >2·5×ULN
Haemoglobin <8 g/dL
Thrombocytopenia: Platelets <100 G/L
Leukopenia: Leukocytes <3 G/L
Neutropenia: Neutrophils < 1.5 G/L
Hypogammaglobulinemia: Serum IgG <400 mg/dL
Active viral, bacterial or fungal infection precluding intensified immunosuppression
Active malignant disease precluding intensified immunosuppressive therapy
Latent or active tuberculosis (positive QuantiFERON-TB-Gold test)
Administration of a live vaccine within 6 weeks of screening
History of alcohol or illicit substance abuse
Serious medical or psychiatric illness likely to interfere with participation in the study
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note