ARGX-117 in Deceased Donor Kidney Transplant Recipients at Risk for Delayed Graft Function

Study Overview
=================
Brief Summary
-----------------
This is a phase 2 study to evaluate the safety, efficacy and tolerability of ARGX-117 in Deceased Donor Kidney Transplant Recipients at Risk for Delayed Graft Function

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study to Assess the Safety, Efficacy, and Tolerability of ARGX-117 in Improving Allograft Function in Recipients of a Deceased Donor Renal Allograft at Risk for Delayed Graft Function

Conditions
-----------------
Delayed Graft Function

Intervention / Treatment
-----------------
* Biological: ARGX-117
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is at least the local legal age of consent for clinical studies and at least aged 18 years and less than 70 years when signing the ICF Is capable of providing signed informed consent and complying with protocol requirements Agree to use contraceptive measures consistent with local regulations Have dry body weight less than 120 kg and body mass index less than 40 kg/m2 at screening Are diagnosed with ESRD and have been stable on chronic dialysis for at least 3 months Are recipients of de novo or second-time, single kidney transplant from a deceased donor, either DCD or DBD Are ABO compatible with donor allograft, except for type A2 donor to type B recipient kidneys Have a negative cross match Have received pretransplant vaccinations for: Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, or are willing to receive the vaccinations approximately 3 to 4 months posttransplant Have received SARS-CoV-2 vaccinations consistent with participating site's requirements Exclusion Criteria: Any known history of complement deficiency Evidence of peritonitis in participants on peritoneal dialysis Received any solid organ, bone marrow, or hematopoietic stem cell transplant, with the exception of prior first kidney transplant Current treatment for an autoimmune disease requiring maintenance immunosuppression to control systemic disease activity that would pose a significant safety risk or put the participant at undue harm in the opinion of the investigator Any history of malignancy unless considered cured by adequate treatment with no evidence of recurrence for more than 5 years before the first administration of IMP. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histological finding of prostate cancer Unwillingness to receive vaccinations consistent with protocol-mandated and participating site requirements Clinically significant active bacterial, viral, or fungal infection or infection with HBV, HCV, HIV or tuberculosis. Clinically significant comorbidity, recent major surgery (within 3 months of screening), history of any treatment nonadherence, or intention to have surgery during the study other than kidney transplantation; or any other medical condition that, in the investigator's opinion, would confound the results of the study or put the participant at undue risk Received a different IMP in another clinical study less than 12 weeks or 5 half-lives (whichever is longer) before screening Currently participating in another interventional clinical study or previously participated in an ARGX-117 clinical study and received at least 1 dose of IMP Known hypersensitivity to ARGX-117 or any of its excipients or to tacrolimus, MMF or mycophenolic acid, or antithymocyte globulin or allergy to Leporidae (eg, rabbit) History (within 12 months before screening) of current alcohol, drug, or medication abuse as assessed by the investigator Pregnant or lactating state or intention to become pregnant during the study Received any prior desensitization therapies or any pretransplant immunosuppressive therapy within 5 half-lives or twice the duration of the biological effect, whichever is longer. The full list is available in the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARGX-117<br>Patients receiving ARGX-117 intravenous infusions | Biological: ARGX-117<br>* Intravenous administration of ARGX-117<br>|
| Placebo Comparator: Placebo<br>Patients receiving placebo intravenous infusions | Other: Placebo<br>* Intravenous administration of placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| eGFR at 24 weeks posttransplant | Estimated glomerular filtration rate | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with Delayed Graft Function (DGF) |  | Up to 52 weeks | 
| Duration of dialysis treatment for DGF within the first 30 days posttransplant (ie, date of last dialysis treatment) |  | up to 30 days | 
| CRR at 72 hours and on study day 8 (posttransplant day 7) | Creatinine reduction ratio | up to 7 days | 
| iBox score at 52 weeks posttransplant |  | up to 52 weeks | 
| Dialysis-free survival through 52 weeks posttransplant |  | up to 52 weeks | 
| eGFR at 52 weeks posttransplant | Estimated glomerular filtration rate | up to 52 weeks | 
| Incidence of PNF (Primary Nonfunction) |  | up to 52 weeks | 
| Serum concentrations for ARGX 117 |  | up to 52 weeks | 
| Values from baseline in free C2, total C2, and CH50 activity |  | up to 52 weeks | 
| Change from baseline in free C2, total C2, and CH50 activity |  | up to 52 weeks | 
| Incidence of ADA against ARGX-117 |  | up to 52 weeks | 
| Prevalence of ADA against ARGX-117 |  | Up to 52 weeks |