Antibody-mediated Rejection
Conditions
Keywords
Active AMR, Chronic active AMR, Late AMR
Brief summary
The purpose of this study is to assess the safety, tolerability, and efficacy of efgartigimod PH20 SC given by a prefilled syringe in participants with Antibody-Mediated Rejection (AMR) after kidney transplantation. After a screening period of up to 6 weeks, eligible participants will be randomized in a 1:1:1 ratio. The study drug will be administered subcutaneously while patients remain on their standard background immunosuppression therapy (tacrolimus, mycophenolate mofetil, steroids) during the treatment period (48 weeks). At the end of the treatment period, the participants will enter an observational/follow-up period (approximately 24 weeks). The participants will be in the study for up to 78 weeks.
Interventions
COMBINATION_PRODUCTEfgartigimod PH20 SC - prefilled syringe
Subcutaneous efgartigimod PH20 SC given by prefilled syringe
OTHERPlacebo PH20 SC - prefilled syringe
Subcutaneous placebo PH20 SC given by prefilled syringe
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* The participant is within the ages of 18 and 80 years old * The participant had a kidney transplant (living or deceased donor) at least 6 months before the study * The participant has received a diagnosis of active or chronic active antibody-mediated rejection (AMR) with detectable donor-specific antibodies at time of the study * A participant may be allowed into the study if they receive the following medications: 1. Received mycophenolate mofetil for at least 20 weeks before the study 2. Has remained on a stable dose of mycophenolate mofetil and tacrolimus for at least 4 weeks before being allowed to participate in the study 3. Has remained on tacrolimus doses between 5 to 10 ng/mL at least 4 weeks before being allowed to participate in the study 4. Steroid dose was between 0 to 10 mg per day of prednisone (or dose equivalent) for at least 4 weeks before being allowed to participate in the study
Exclusion criteria
* Confirmed T-cell or mixed rejection at time of the study * Recent change in immunosuppressive therapy agents * Any other medical condition that, in the investigator's opinion, would interfere with the results of the study or put the participant at undue risk * Pregnant or lactating state or intention to become pregnant during the study The complete list of criteria can be found in the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events (AEs) | Up to 78 weeks |
| Percentage of participants with permanent treatment discontinuation due to adverse events (AEs) | Up to 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline (slope) of the estimated glomerular filtration rate (eGFR) | Up to 72 weeks | — |
| Histological changes in kidney biopsy | Up to 72 weeks | — |
| Urine protein creatinine ratio (UPCR) | Up to 72 weeks | — |
| Graft and participant survival | Up to 72 weeks | — |
| Proportion of participants with biopsy-proven histologic resolution (BPHR) over time | Up to 72 weeks | — |
| Changes from baseline in AMR/MVI index score over time | Up to 72 weeks | MVI: microvascular inflammation. AMR/MVI score is a continuous index derived from Banff histological lesions (g, ptc, cg, and C4d positivity) and used to quantify the intensity of microvascular inflammation linked to AMR. It aims to describe where a biopsy lies along the spectrum from no rejection to probable AMR to complete AMR/MVI, providing a more granular measure of disease severity than dichotomous Banff categories. |
| Percentage change from baseline in total IgG levels in serum over time | Up to 60 weeks | — |
| Efgartigimod serum concentration-time profile and PK parameter Ctrough | Up to 48 weeks | — |
| Incidence of antidrug antibodies (ADA) against efgartigimod in serum over time | Up to 72 weeks | — |
| Incidence of antibodies against rHuPH20 in plasma over time | Up to 72 weeks | — |
Countries
Austria, Belgium, Canada, Czechia, France, Germany, Spain, United States
Outcome results
None listed