Clinical trial NCT04935177: Renal Function in Highly Sensitized Patients 1 Year After Desensitization With Imlifidase Prior to DD Kidney Tx
Official title: An Open-label, Controlled, Randomized Phase 3 Trial Evaluating 12-month Kidney Function in Highly Sensitized (cPRA ≥99.9%) Kidney Tx Patients With Positive XM Against a Deceased Donor, Comparing Desensitization Using Imlifidase With SoC
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Kidney Transplantation in Highly Sensitized Patients
Keywords: Desensitization
Highly sensitized
Positive crossmatch
Unlikely to be transplanted
Renal transplantation
Deceased donor
Lead sponsor: Hansa Biopharma AB
Sponsor class: INDUSTRY
First posted: 2021-06-22
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, controlled and randomized
Primary purpose: TREATMENT

Brief summary: An open-label, controlled, randomized Phase 3 trial evaluating 12-month kidney function in highly sensitized (cPRA ≥99.9%) kidney transplant patients with positive crossmatch against a deceased donor, comparing desensitization using imlifidase with standard of care

Detailed description: After being informed about the study and potential risks, all patients giving written informed consent will undergo pre-screening to determine eligibility for study entry.

Once an organ offer is received, a virtual crossmatch (vXM) is performed. If the crossmatch is considered predictive of a positive flow cytometry crossmatch (FCXM), the patient will be evaluated if eligible to receive the desensitization currently in use at the study site. Subsequently the patient will be randomized in a 1:1 ratio to the imlifidase or the control arm.

If the patient is randomized to the imlifidase arm, the organ will be accepted and shipped, and the patient will proceed to imlifidase treatment (generally within 24 h prior to transplantation) followed by transplantation. If the patient is randomized to the control arm, transplantation made possible by the local desensitization regimen will occur. If the institution-specific desensitization protocol is deemed not to be successful, the organ offer will be turned down, and the patient will remain active on the waiting list and remain in the trial, while the kidney will be allocated to another recipient through the kidney allocation system (KAS).

All transplanted patients will receive induction therapy and maintenance immunosuppression. All patients will be followed for 12 months.

Estimated glomerular filtration rate (eGFR) will be assessed 12 months after randomization as the primary endpoint reasonably likely to predict a clinical benefit in patient survival.

All patients with donor specific antibodies (DSA) are at risk of developing antibody-mediated rejection (AMR). Imlifidase removes DSA quickly and efficiently at the time of transplantation but, as with other desensitization methods, the antibodies are expected to re-occur after transplantation. In the imlifidase treatment arm, and for desensitized control arm patients, protocol kidney biopsies will be performed at the time of transplantation and at 1 year after transplantation.

Eligibility criteria: Inclusion Criteria:

* Signed Informed Consent obtained before any trial-related procedures
* Male or female age 18-70 years at the time of screening
* 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
* Original calculated panel reactive antibody (cPRA) ≥99.9%
* Virtual crossmatch (vXM), predictive of a positive crossmatch to an available deceased donor (DD)
* Willingness and ability to comply with the protocol
* Willingness to participate in the planned 4-year extension trial

Exclusion Criteria:

* High dose IVIg (2 g/kg) treatment within 28 days prior to imlifidase treatment
* Previous treatment with imlifidase
* Breast feeding or pregnancy
* Women of child-bearing potential not willing or able to practice FDA-approved forms of contraception, or abstinence. Two medically acceptable methods of highly effective contraception must be used for the duration of the study (e.g. oral, transdermal, intravaginal, injectable or implantable contraceptive; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; bilateral tubal occlusion; or double barrier method). For a woman to be considered postmenopausal this ascertainment must be made according to medical records and clinical history and may be aided by measurement of elevated postmenopausal serum gonadotropin levels (FSH).
* ABO blood group incompatible transplantations (A2 or A2B kidneys will not be accepted for B recipients)
* Positive serology for human immunodeficiency virus (HIV)
* Clinical signs of hepatitis B virus (HBV) or hepatitis C virus (HCV) infections
* Clinical signs of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infections
* Positive test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (according to local hospital routines)
* Active tuberculosis
* 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)
* Any condition that in the view of the Investigator precludes transplantation
* History of a proven hypercoagulable condition
* Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
* Intake of investigational drugs within 5 half-lives of the drug or 3 months, whichever is the longest
* Contemporaneous participation in a medical device study
* Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities
* Inability by the judgement of the investigator to participate in the trial for any other reason

Primary outcomes:
measure: Mean estimated glomerular filtration rate (eGFR) at 12 months
timeFrame: 12 months after randomization
Secondary outcomes:
measure: Patient survival at 12 months
timeFrame: 12 months after randomization
Other outcomes:
measure: Frequency of dialysis dependency at 12 months
timeFrame: 12 months after randomization
measure: Graft failure-free survival at 12 months
timeFrame: 12 months after randomization
measure: Graft survival at 12 months
timeFrame: 12 months after randomization
measure: Frequency of wait-list categories at 12 months
timeFrame: 12 months after randomization
measure: Frequency of delayed graft function
timeFrame: Within 7 days after transplantation
measure: Antibody-mediated rejection (AMR) frequency
timeFrame: During 12 months after randomization
measure: Cell-mediated rejection (CMR) frequency
timeFrame: During 12 months after randomization
measure: Conversion of positive crossmatch test to negative
timeFrame: Within 4 hours after imlifidase treatment
measure: Donor specific antibody (DSA) levels for all antibodies with a mean fluorescence intensity (MFI) of ≥1000
timeFrame: Prior first dose, 2, 4, 24, 48, 72 h and Days 5, 6, 8,15 and Months 1, 3, 6, 8, 10, and 12
measure: Anti-drug antibodies (ADA)
timeFrame: Prior first dose, 48 hours, Days 8, 15, and Months 1, 2, 3, 6, 8, 10, and 12
measure: Imlifidase pharmacokinetics (AUC)
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 15
measure: Imlifidase pharmacokinetics (Cmax)
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 15
measure: Imlifidase pharmacokinetics (tmax)
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 15
measure: Imlifidase pharmacokinetics (t1/2)
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 15
measure: Imlifidase pharmacokinetics (CL)
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 15
measure: Imlifidase pharmacokinetics (Vz)
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 15
measure: Imlifidase pharmacodynamics
timeFrame: Within 24 hours prior to imlifidase treatment and up to Day 10
measure: Safety as measured by adverse events (AEs)
timeFrame: From signing informed consent to 12 months
measure: Safety as measured by serious adverse events (SAEs)
timeFrame: From signing informed consent to 12 months
measure: Safety as measured by other adverse events (AEs)
timeFrame: From signing informed consent to 12 months
measure: Change in patient-reported life participation, as measured by PROMIS-SF-8a
timeFrame: At pre-screening and at 12 months after randomization
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) Hospital
state: Alabama
city: Phoenix
country: United States
facility: Banner Health - University Medical Center - Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: Keck Hospital of University of Southern California (USC)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: Sutter Health - California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) Medical Center
state: California
city: Washington
country: United States
facility: Georgetown Transplant Institute
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University (NYU) Langone Transplant Institute, NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: New York-Presbyterian - Weill Cornell Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania, Penn Medicine
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital Specialty and Transplant
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Hansa Biopharma AB
name: Clinical Operations
role: STUDY_DIRECTOR
References: