VEL-101 to Prevent Rejection After Kidney Transplantation

Official title

A Phase 2, Randomized, Partially Blinded, Controlled, Dose-ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VEL-101 in Kidney Transplant Recipients.

Overview

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

• Drug Tacrolimus (TAC)
  Tacrolimus Immediate Release in addition to SOC
• Drug VEL-101
  VEL-101 in addition to SOC

Primary outcome measures

• Incidence of serious adverse events (SAEs) [Time frame: Month 12]
• Incidence of treatment emergent adverse events (TEAEs) [Time frame: Month 12]
• PK Parameter Cmax [Time frame: Day 1, Month 3]
• PK Parameter Cmin [Time frame: Day 1, Month 3]
• PK Parameter Tmax [Time frame: Day 1, Month 3]
• AUC from 0-8 hours [Time frame: Day 1, Month 3]
• AUC from 0 to 48 hours [Time frame: Day 2]
• VEL-101 Accumulation Ratio [Time frame: Month 3]
• VEL-101 Pre-Dose Serum Concentration [Time frame: Day 1, Day 14, Months 1, 2, 3, 6, 9, 12, Periprocedural (kidney biospy)]
• Effect of Anti-Drug Antibody (ADA) Development on VEL-101 Serum Concentration [Time frame: Months 1, 2, 3, 6, 9, 12, Periprocedural (kidney biopsy)]

Secondary outcome measures (12)

• Percentage Participants Meeting Composite Endpoint [Time frame: Month 12]
• Slope of estimated glomerular filtration rage (eGFR) [Time frame: Month 12]
• Incidence Injection Site Reaction [Time frame: Month 12]
• Incidence Adverse Events of Special Interest (AESIs) [Time frame: Month 12]
• Proportion of Participants Discontinuing due to Adverse Events [Time frame: Month 12]
• Incidence Delayed Graft Function Delayed Graft Function [Time frame: Day 28]
• Duration Delayed Graft Function [Time frame: Day 28]
• Incidence of Renal Replacement Therapy (RRT) [Time frame: Month 12]
• Duration of Renal Replacement Therapy (RRT) [Time frame: Month 12]
• Incidence of New-Onset Diabetes after Transplantation (NODAT) [Time frame: Month 12]
• Effect of Anti-Drug Antibody (ADA) Formation on VEL-101 t1/2 (hours) [Time frame: 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) [Time frame: Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy)]

Eligibility criteria

Inclusion criteria

• Greater than or equal to 18 years of age
• 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.
• 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.
• 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.
• 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

• Able \& willing to comply with all study procedures, including PK and PD assessments, as assessed by the Investigator
• Vaccination up to date per the center's SOC as assessed by the Investigator.
• In the opinion of the Investigator, is able to adhere to the study requirements.

Exclusion criteria

• Negative for EBV or Epstein-Barr nuclear antigen antibody
• 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.
• History of previous non-kidney solid organ, vascular composite allograft, pancreatic islet, stem cell or bone marrow transplant.
• Planned multiorgan transplant, including dual or en-bloc kidney transplant
• Anticipated cold ischemia time (CIT) >30 hours
• Donor with Kidney Donor Profile Index (KDPI) > 85%
• Panel reactive antibody >80%, calculated panel-reactive antibody (CPRA)>80% or history of HLA desensitization
• Positive T or B cell flow, cytotoxic, or virtual crossmatch at Screening
• Current or historical DSA
• 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
• Recipient who is CMV IgG negative (R-) receiving a kidney from a donor who is CMV IgG positive (D+)
• Thrombocytopenia (platelets < 75,00/mm3), leukopenia (white blood cells \[WBC\] <3,000/mm3), or anemia (hemoglobin <8 g/dL) at Screening
• History of inadequately treated active or latent mycobacterium tuberculosis (TB) infection
• Clinically significant abnormality on 12-lead electrocardiogram (ECG) at Screening, as determined by the Investigator
• Positive pregnancy test or lactating at Screening with plans to continue lactating regimen throughout the study
• 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
• 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
• Medical condition requiring chronic use of daily prednisone doses >5 mg (or equivalent)
• 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.

• Participation in an investigational study within 30 days or within 5 half-lives of the investigational agent, whichever is longer, prior to Screening
• Receiving any antibody or biologic medicinal product (with the exception of erythropoietin products) within 90 days prior to Screening
• Positive test for SARS-CoV-2 antigen, polymerase chain reaction (PCR), or equivalent testing, at Screening, if performed
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07290777 · VEL-101.KI201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗