VEL-101 to Prevent Rejection After Kidney Transplantation (RENGEVITY-201)

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.

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

Study Overview

• Status: Not yet recruiting
• Conditions: Transplantation, Kidney
• Intervention / Treatment: Drug: VEL-101; Drug: Tacrolimus (TAC)

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 844-835-6947 or 1-984-309-4040; Email: medinfo@veloxis.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tacrolimus	Drug: Tacrolimus (TAC); Tacrolimus Immediate Release in addition to SOC
Experimental: VEL-101 Low Dose	Drug: VEL-101; VEL-101 in addition to SOC; Other Names: Pegrizeprument; FR104
Experimental: VEL-101 High Dose	Drug: VEL-101; VEL-101 in addition to SOC; Other Names: Pegrizeprument; FR104

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of serious adverse events (SAEs)	Incidence of serious adverse events (SAEs)	Month 12
Incidence of treatment emergent adverse events (TEAEs)	Incidence of treatment emergent adverse events (TEAEs)	Month 12
PK Parameter Cmax	PK Parameter Cmax	Day 1, Month 3
PK Parameter Cmin	PK Parameter Cmin	Day 1, Month 3
PK Parameter Tmax	PK Parameter Tmax	Day 1, Month 3
AUC from 0-8 hours	AUC from 0-8 hours	Day 1, Month 3
AUC from 0 to 48 hours	AUC from 0 to 48 hours	Day 2
VEL-101 Accumulation Ratio	VEL-101 Accumulation Ratio	Month 3
VEL-101 Pre-Dose Serum Concentration	VEL-101 Pre-Dose Serum Concentration	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	Effect of Anti-Drug Antibody (ADA) Development on VEL-101 Serum Concentration	Months 1, 2, 3, 6, 9, 12, Periprocedural (kidney biopsy)
Effect of Neutralizing Antibody (NAb) 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)
VEL-101 CD28 Receptor Occupancy 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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Participants Meeting Composite Endpoint	Death, graft failure or biopsy proven acute rejection (BPAR, T cell mediated rejection [TCMR] Banff Grade > or = to 1A or antibody-mediated rejection [AMR] )	Month 12
Slope of estimated glomerular filtration rage (eGFR)	Slope of estimated glomerular filtration rage (eGFR)	Month 12
Incidence Injection Site Reaction	Incidence Injection Site Reaction	Month 12
Incidence Adverse Events of Special Interest (AESIs)	AESIs Including BK viremia, BK virus-associate nephropathy, EBV viremia, PTLD, CMV viremia, CMV disease, malignancies	Month 12
Proportion of Participants Discontinuing due to Adverse Events	Proportion of Participants Discontinuing due to Adverse Events	Month 12
Incidence Delayed Graft Function Delayed Graft Function	Incidence Delayed Graft Function	Day 28
Duration Delayed Graft Function	Duration Delayed Graft Function	Day 28
Incidence of Renal Replacement Therapy (RRT)	Incidence of Renal Replacement Therapy (RRT)	Month 12
Duration of Renal Replacement Therapy (RRT)	Duration of Renal Replacement Therapy (RRT)	Month 12
Incidence of New-Onset Diabetes after Transplantation (NODAT)	Incidence of New-Onset Diabetes after Transplantation (NODAT)	Month 12
Effect of Anti-Drug Antibody (ADA) Formation on VEL-101 t1/2 (hours)	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) Development on VEL-101 Volume of distribution (liters)	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 Development on VEL-101 Cmin (ng/mL)	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 Cmax (ng/mL)	Effect of Anti-Drug Antibody Development on VEL-101 Cmax (ng/mL)	Months 1, 2, 3, 6, 9, 12 and Periprocedural (kidney biopsy)

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: transplant; renal; prophylaxis; kidney; Kidney transplant; VEL-101; pegrizeprument; renal allograft rejection; CD28 inhibitor; monoclonal antibody fragment; FR-104; Anti-CD28
• Additional Relevant MeSH Terms: Organic Chemicals; Macrolides; Lactones; Tacrolimus
• Other Study ID Numbers: VEL-101.KI201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No