Transplantation, Kidney
Conditions
Keywords
Kidney transplant, VEL-101, pegrizeprument, renal allograft rejection, prophylaxis, kidney, renal, transplant, CD28 inhibitor, monoclonal antibody fragment, FR-104, Anti-CD28
Brief summary
This study will evaluate the safety and efficacy of VEL-101 compared with tacrolimus in patients undergoing kidney transplantation.
Detailed description
This study is a randomized, multicenter, partially blinded, active control study to evaluate the safety and effectiveness of VEL-101 compared with tacrolimus in the prevention of rejection in patients undergoing kidney transplantation. Up to 120 de novo kidney transplant recipients will receive rATG with corticosteroids (CS), and mycophenolate as maintenance therapy, and will be randomized 1:1:1 to receive either VEL-101 (low dose or high dose) or tacrolimus.
Interventions
DRUGTacrolimus (TAC)
Tacrolimus Immediate Release in addition to SOC
DRUGVEL-101
VEL-101 in addition to SOC
Sponsors
Veloxis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Investigator/participant blinded to VEL-101 dose level but not blinded to participants receiving tacrolimus.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Greater than or equal to 18 years of age 2. Able to understand key components of the study as described in the written informed consent document and willing and able to provide written informed consent. 3. If female, surgically sterile (post hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), postmenopausal (greater than 12 months of amenorrhea without alternative medical causes), or, if of childbearing potential, is using a highly effective contraception until 90 days after EOS visit. 4. If male, is vasectomized, has undergone bilateral orchidectomy, agrees to abstinence of heterosexual intercourse, or only has female partner using highly effective contraception, surgically sterile or postmenopausal and agrees to use method until 90 days after EOS visit. 5. Receiving kidney allograft from deceased donor or non-human leukocyte antigen (HLA) identical living donor. a) Repeat kidney transplant allowed if no previous kidney transplant(s) failed due to recurrent disease within first year, acute rejection or nonsurgical thrombosis 6. Able & willing to comply with all study procedures, including PK and PD assessments, as assessed by the Investigator 7. Vaccination up to date per the center's SOC as assessed by the Investigator. 8. In the opinion of the Investigator, is able to adhere to the study requirements.
Exclusion criteria
1. Negative for EBV or Epstein-Barr nuclear antigen antibody 2. Know allergy to study medication (rATG, corticosteroids, MMF, tacrolimus, or VEL-101) or its components or a history of a severe allergic reaction to any drug. 3. History of previous non-kidney solid organ, vascular composite allograft, pancreatic islet, stem cell or bone marrow transplant. 4. Planned multiorgan transplant, including dual or en-bloc kidney transplant 5. Anticipated cold ischemia time (CIT) \>30 hours 6. Donor with Kidney Donor Profile Index (KDPI) \> 85% 7. Panel reactive antibody \>80%, calculated panel-reactive antibody (CPRA)\>80% or history of HLA desensitization 8. Positive T or B cell flow, cytotoxic, or virtual crossmatch at Screening 9. Current or historical DSA 10. Recipient or donor with positive hepatitis B surface antigen (HBsAG), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV) nucleic acid testing (NAT), hepatitis C virus (HCV) antibody, HCV NAT, human immunodeficiency virus (HIV), or HIV NAT 11. Recipient who is CMV IgG negative (R-) receiving a kidney from a donor who is CMV IgG positive (D+) 12. Thrombocytopenia (platelets \< 75,00/mm3), leukopenia (white blood cells \[WBC\] \<3,000/mm3), or anemia (hemoglobin \<8 g/dL) at Screening 13. History of inadequately treated active or latent mycobacterium tuberculosis (TB) infection 14. Clinically significant abnormality on 12-lead electrocardiogram (ECG) at Screening, as determined by the Investigator 15. Positive pregnancy test or lactating at Screening with plans to continue lactating regimen throughout the study 16. History of malignancy within the past 5 years (with the exception of non-metastatic basal or squamous cell carcinoma of the skin with successful treatment), or current active malignancy 17. Liver disease, defined as having elevated aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than three times the upper value of the normal range of the study center at Screening 18. Medical condition requiring chronic use of daily prednisone doses \>5 mg (or equivalent) 19. End-stage renal disease caused by primary focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy, or monoclonal gammopathy of kidney significance a) Note: participants with an unknown cause of ESRD can be included. 20. Participation in an investigational study within 30 days or within 5 half-lives of the investigational agent, whichever is longer, prior to Screening 21. Receiving any antibody or biologic medicinal product (with the exception of erythropoietin products) within 90 days prior to Screening 22. Positive test for SARS-CoV-2 antigen, polymerase chain reaction (PCR), or equivalent testing, at Screening, if performed 23. History or presence of coagulopathy, thrombophilia, unexplained bleeding or clotting disorders, or use of systemic anticoagulants at the time of transplant, with the exception of uremic coagulopathy or prophylactic heparin preparations. 24. History or presence, upon clinical evaluation, of any illness or condition that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the participant at undue risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of serious adverse events (SAEs) | Month 12 | Incidence of serious adverse events (SAEs) |
| Incidence of treatment emergent adverse events (TEAEs) | Month 12 | Incidence of treatment emergent adverse events (TEAEs) |
| PK Parameter Cmax | Day 1, Month 3 | PK Parameter Cmax |
| PK Parameter Cmin | Day 1, Month 3 | PK Parameter Cmin |
| PK Parameter Tmax | Day 1, Month 3 | PK Parameter Tmax |
| AUC from 0-8 hours | Day 1, Month 3 | AUC from 0-8 hours |
| AUC from 0 to 48 hours | Day 2 | AUC from 0 to 48 hours |
| VEL-101 Accumulation Ratio | Month 3 | VEL-101 Accumulation Ratio |
| VEL-101 Pre-Dose Serum Concentration | Day 1, Day 14, Months 1, 2, 3, 6, 9, 12, Periprocedural (kidney biospy) | VEL-101 Pre-Dose Serum Concentration |
| Effect of Anti-Drug Antibody (ADA) Development on VEL-101 Serum Concentration | Months 1, 2, 3, 6, 9, 12, Periprocedural (kidney biopsy) | Effect of Anti-Drug Antibody (ADA) Development on VEL-101 Serum Concentration |
| Effect of Neutralizing Antibody (NAb) Development on VEL-101 Serum Concentration | Day 1, Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy) | Effect of Neutralizing Antibody (NAb) Development on VEL-101 Serum Concentration |
| VEL-101 CD28 Receptor Occupancy Concentration (%) | Days 1, 2, 3, 4, 5, 7, 14, 42, 70, 82, 91, 98 and Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy) | VEL-101 CD28 Receptor Occupancy Concentration (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Anti-Drug Antibody Development on VEL-101 Cmin (ng/mL) | Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy) | Effect of Anti-Drug Antibody Development on VEL-101 Cmin (ng/mL) |
| Percentage Participants Meeting Composite Endpoint | Month 12 | Death, graft failure or biopsy proven acute rejection (BPAR, T cell mediated rejection \[TCMR\] Banff Grade \> or = to 1A or antibody-mediated rejection \[AMR\] ) |
| Effect of Anti-Drug Antibody Development on VEL-101 Cmax (ng/mL) | Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy) | Effect of Anti-Drug Antibody Development on VEL-101 Cmax (ng/mL) |
| Slope of estimated glomerular filtration rage (eGFR) | Month 12 | Slope of estimated glomerular filtration rage (eGFR) |
| Incidence Injection Site Reaction | Month 12 | Incidence Injection Site Reaction |
| Incidence Adverse Events of Special Interest (AESIs) | Month 12 | AESIs Including BK viremia, BK virus-associate nephropathy, EBV viremia, PTLD, CMV viremia, CMV disease, malignancies |
| Proportion of Participants Discontinuing due to Adverse Events | Month 12 | Proportion of Participants Discontinuing due to Adverse Events |
| Incidence Delayed Graft Function Delayed Graft Function | Day 28 | Incidence Delayed Graft Function |
| Duration Delayed Graft Function | Day 28 | Duration Delayed Graft Function |
| Incidence of Renal Replacement Therapy (RRT) | Month 12 | Incidence of Renal Replacement Therapy (RRT) |
| Duration of Renal Replacement Therapy (RRT) | Month 12 | Duration of Renal Replacement Therapy (RRT) |
| Incidence of New-Onset Diabetes after Transplantation (NODAT) | Month 12 | Incidence of New-Onset Diabetes after Transplantation (NODAT) |
| Effect of Anti-Drug Antibody (ADA) Formation on VEL-101 t1/2 (hours) | Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy) | Effect of Anti-Drug Antibody (ADA) Formation on VEL-101 t1/2 (hours) |
| Effect of Anti-Drug Antibody (ADA) Development on VEL-101 Volume of distribution (liters) | Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy) | Effect of Anti-Drug Antibody (ADA) Development on VEL-101 Volume of distribution (liters) |
Contacts
Primary ContactStudy Director
Outcome results
None listed