VEL-101 to Prevent Rejection After Kidney Transplantation

Официальное название

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.

Обзор

This study will evaluate the safety and efficacy of VEL-101 compared with tacrolimus in patients undergoing kidney transplantation.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Incidence of serious adverse events (SAEs) [Срок оценки: Month 12]
• Incidence of treatment emergent adverse events (TEAEs) [Срок оценки: Month 12]
• PK Parameter Cmax [Срок оценки: Day 1, Month 3]
• PK Parameter Cmin [Срок оценки: Day 1, Month 3]
• PK Parameter Tmax [Срок оценки: Day 1, Month 3]
• AUC from 0-8 hours [Срок оценки: Day 1, Month 3]
• AUC from 0 to 48 hours [Срок оценки: Day 2]
• VEL-101 Accumulation Ratio [Срок оценки: Month 3]
• VEL-101 Pre-Dose Serum Concentration [Срок оценки: 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 [Срок оценки: Months 1, 2, 3, 6, 9, 12, Periprocedural (kidney biopsy)]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07290777 · VEL-101.KI201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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