(TNX-1500) in Kidney Transplant Recipients

Official title

Phase II Clinical Trial Evaluating the Safety and Efficacy of Fc-Modified Anti-CD154 mAB (TNX-1500) in Kidney Transplant Recipients

Overview

The primary objective is to investigate the safety and efficacy of TNX-1500, an FC-modified anti-CD154 mAb, in five kidney transplant recipients at 12 months.

Interventions

• Drug TNX-1500
  This is an open-label, single-center, single-arm study to assess the safety and efficacy of TNX-1500, an Fc-modified anti-DF154 mAb in five adult kidney transplant recipients.
• Procedure Kidney Transplant
  Kidney Transplant

Primary outcome measures

• Number of Adverse Events in each subject [Time frame: 12 Months]
• Number of Serious Adverse Events in each subject [Time frame: 12 Months]

Secondary outcome measures (9)

• Incidence of Biopsy Proven Acute Rejection [Time frame: 12 months]
• Incidence of treatment for acute rejection [Time frame: 12 Months]
• Incidence of de novo DSA development [Time frame: Months 1, 3, 6, 9, 12]
• Incidence of serious opportunistic infections and malignancies [Time frame: 12 months]
• GFR measurement [Time frame: 12 months]
• Incidence of death [Time frame: 12 months]
• Incidence of graft loss [Time frame: 12 months]
• Degree of Proteinuria [Time frame: 12 Months]
• Degree of albuminuria [Time frame: 12 Months]

Eligibility criteria

Inclusion criteria

• Male or female subjects ≥18 to 75 years of age.
• Kidney transplant candidates with chronic kidney disease (stage IV or V) or end-stage kidney disease evaluated and listed for transplantation at Massachusetts General Hospital.
• Recipient of an ABO-compatible, non-human leukocyte antigen (HLA) identical living or deceased donor kidney (de novo or second transplant)
• Ability to understand the study requirements and provide written informed consent.
• Epstein-Barr virus (EBV) seropositive

Exclusion criteria

• Recipient seropositive for human immunodeficiency virus (HIV-1), or hepatitis B surface antigen (HBsAg) or core antibody (Anti-HBc); subjects who are seropositive for hepatitis C virus (HCV) are excluded without proof of sustained viral response (SVR) after anti-HCV treatment or spontaneous clearance.
• Recipient of a kidney from a donor who tests positive for HIV, HBsAg, Anti-HBc, or HCV NAT.
• Subjects with a severe systemic infection, current or within the 2 weeks prior to screening.
• Left ventricular ejection fraction < 40% as determined by TTE or clinical evidence of heart failure.
• Pregnant or nursing (lactating) women confirmed by human chorionic gonadotropin (hCG) laboratory test.
• Women of childbearing potential (women capable of becoming pregnant) unless using a highly effective method of contraception during dosing and for 24 weeks after study treatment. Highly effective contraception methods include:

• Female sterilization (surgical, bilateral oophorectomy with or without hysterectomy), or tubal ligation at least 6 weeks before taking study treatment.
• Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partners should be the sole partners for that subject.
• Use of injected or implanted hormonal methods of contraception or other hormonal contraception that have comparable efficacy (<1% for example, hormone vaginal ring or placement of a long-acting reversible contraceptives, an intrauterine device, or intrauterine system.
• Total abstinence
• Use of other investigational products or enrollment in another investigational drug study within 30 days prior to screening or 5 half-lives, whichever is longer.
• Subjects with clinically significant lab abnormalities (>2.5 x the upper limit of normal (ULN) of the following liver function chemistries unless due to, as judged by the investigator, a benign underlying condition:

• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Alkaline phosphatase (ALP)
• Bilirubin
• Coagulation studies (international normalization ratio (INR), prothrombin time (PT), and partial thromboplastin time (PTT))
• Any other clinically significant medical condition, active infection, laboratory abnormality, or psychosocial condition (e.g. history of substance use disorder) that would, in the judgement of the investigator, impact the subject's ability to participate in the trial.
• Subject receives an organ at high risk for delayed graft function, including from a deceased donor after cardiac death (DCD) or a high Kidney Donor Profile Index ≥85%.
• Presence of pre-existing donor-specific antibodies (DSA) or calculated panel reactive antibodies (cPRA) >20% based upon results within 6 months prior to transplant.
• Virtual crossmatch (VXM) positive transplant with an MFI >1000 as assessed by routine methodology (Luminex)
• Cytomegalovirus (CMV) high risk combination: donor positive to recipient negative
• Multi-organ transplant or tissue recipient.
• History of malignancy of any organ system, except for localized excised non-melanomatous skin or carcinoma in situ of the cervix
• Subjects with any of the following: hemoglobin <8 mg/dL, white blood cell ≤2,000/mm3, or platelet count ≤75,000/mm3.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Massachusetts General Hospital — Boston
• Massachusetts General Hospital — Boston

Identifiers

NCT: NCT07204080 · 2025P-------

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗