Evaluating Safety and Efficacy of TOL101 Induction Versus Anti-Thymocyte Globulin to Prevent Kidney Transplant Rejection

Summary

Induction therapy with antibodies is administered during transplant surgery and for a short period of time following transplant surgery in an effort to render the immune system less able to mount an initial rejection response. In general, induction therapy is associated with better outcomes compared to the absence of induction therapy. However, currently used induction agents, some of which are not labeled or indicated for induction therapy in transplantation, have drawbacks related to long-term immune system suppression increasing susceptibility to opportunistic infections or malignancies, and other immune-mediated side effects.

An unmet medical need exists for a more specific approach to prevent acute organ rejection, without unnecessarily exposing the patient to non-specific or open-ended immune suppression, which may exacerbate the risks of infections and malignancies. TOL101 is a novel antibody that targets a very specific immune cell type that is critical in the acute organ rejection response. In this two-part study, TOL101 will be evaluated for the prophylaxis of acute organ rejection when used as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus in first time kidney transplant recipients.

This study will test the hypothesis that a more specific approach (with TOL101) to prevention of acute organ rejection may provide similar or better efficacy than the currently used induction antibodies (such as Anti-Thymocyte Globulin or Thymoglobulin) while carrying fewer risks in terms of opportunistic infections, malignancies and adverse effects.

Conditions

• End Stage Renal Disease
• Renal Transplant

Interventions

DRUG

Anti-Thymocyte Globulin

1.5mg/kg IV on Day of Transplant and 1.0-1.5 mg/kg IV once daily for a minimum of 4.5mg/kg and a maximum of 7.5mg/kg total cumulative dose

DRUG

TOL101

Potential Therapeutic Dose (PTD)-A (0.28-56 mg to be determined in Phase 1/Part A ) IV once daily x 6-10 doses starting on Day of Transplant

DRUG

TOL101

Potential Therapeutic Dose (PTD)-B (0.28-56 mg to be determined in Phase 1/Part A ) IV once daily x 6-10 doses starting on Day of Transplant

DRUG

Steroids

IV methylprednisolone prior to first 3 doses of study drug; oral prednisone tapered to 5-10 mg over 6 months

DRUG

Tacrolimus

Oral administration started by 6 days post-transplantation and continued for 6 months

DRUG

Mycophenolate mofetil (MMF)

Oral administration started by Day 1 post-transplantation and continued for 6 months

Sponsors & Collaborators

• Tolera Therapeutics, Inc

  lead INDUSTRY

Principal Investigators

• Stuart Flechner, MD · The Cleveland Clinic

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-07-31

Primary Completion

2013-06-30

Completion

2013-06-30

Countries

• United States

Study Locations