(TNX-1500) in Kidney Transplant Recipients

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

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

Inclusion Criteria:

1. Male or female subjects ≥18 to 75 years of age.
2. 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.
3. Recipient of an ABO-compatible, non-human leukocyte antigen (HLA) identical living or deceased donor kidney (de novo)
4. Ability to understand the study requirements and provide written informed consent.
5. Epstein-Barr virus (EBV) seropositive

Exclusion Criteria:

1. 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.

2. Recipient of a kidney from a donor who tests positive for HIV, HBsAg, Anti-HBc, or HCV NAT.

3. Subjects with a severe systemic infection, current or within the 2 weeks prior to screening.

4. Left ventricular ejection fraction < 40% as determined by TTE or clinical evidence of heart failure.

5. Any of the following ocular history or ocular findings at screening exam:

   1. Active inflammation in either or both eyes (does not include pigment cell in the AC after dilation); must be greater than trace cell or trace flare to exclude.
   2. Findings that would impact the ability to monitor, diagnose, manage, and follow new onset ocular inflammation.
   3. Receipt of ocular corticosteroids (topically, intravitreally, or periocularly) or has been treated with anti-VEGF intravitreal therapy within three months of Screening Exam

6. Pregnant or nursing (lactating) women confirmed by human chorionic gonadotropin (hCG) laboratory test.

7. 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:

   1. Female sterilization (surgical, bilateral oophorectomy with or without hysterectomy), or tubal ligation at least 6 weeks before taking study treatment.
   2. 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.
   3. 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.
   4. Total abstinence

8. 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.

9. 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:

   1. Alanine aminotransferase (ALT)
   2. Aspartate aminotransferase (AST)
   3. Alkaline phosphatase (ALP)
   4. Bilirubin
   5. Coagulation studies (international normalization ratio (INR), prothrombin time (PT), and partial thromboplastin time (PTT))

10. 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.

11. Presence of pre-existing donor-specific antibodies (DSA) or calculated panel reactive antibodies (cPRA) >20% based upon results within 6 months prior to transplant.

12. Virtual crossmatch (VXM) positive transplant with an MFI >1000 as assessed by routine methodology (Luminex)

13. Cytomegalovirus (CMV) high risk combination: donor positive to recipient negative

14. Multi-organ transplant or tissue recipient.

15. History of malignancy of any organ system, except for localized excised non-melanomatous skin or carcinoma in situ of the cervix

16. Subjects with any of the following: hemoglobin <8 mg/dL, white blood cell ≤2,000/mm3, or platelet count ≤75,000/mm3.