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

Information source: Tolera Therapeutics, Inc
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: End Stage Renal Disease; Renal Transplant

Intervention: Anti-Thymocyte Globulin (Drug); TOL101 (Drug); TOL101 (Drug); Steroids (Drug); Tacrolimus (Drug); Mycophenolate mofetil (MMF) (Drug)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: Tolera Therapeutics, Inc

Official(s) and/or principal investigator(s):
Stuart Flechner, MD, Principal Investigator, Affiliation: The Cleveland Clinic


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.

Clinical Details

Official title: A Two Part, Phase 1/2, Safety, PK and PD Study of TOL101, an Anti-TCR Monoclonal Antibody for Prophylaxis of Acute Organ Rejection in Patients Receiving Renal Transplantation

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To assess the safety and tolerability of ascending doses of TOL101 and the effectiveness of TOL101 to target and downregulate T cells in patients undergoing first renal transplantation

Secondary outcome:

The effects of ascending doses of TOL101 on CD3+ T lymphocyte numbers and other immune cell subsets

The pharmacokinetic (PK) profile of TOL101 in renal transplant recipients and the exposure-response (PK parameter to CD3+ T lymphocyte numbers) relationship over time

Biopsy-proven acute organ rejection

Graft survival

Patient survival

Renal function by measured GFR at 6 months post-transplant and urine protein to creatinine ratio at 3 and 6 months post-transplant

Delayed graft function

Immunogenicity of TOL101 by measurement of anti-TOL101 antibodies

The presence of Donor Specific Antibody at 3 months (Part B only) and 6 months post-transplant


Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.


Inclusion Criteria:

- Recipient of a primary renal transplant from a living or standard criteria cadaveric


- Male or female 18-60 years of age

- Recipient with a PRA < 20%

Exclusion Criteria:

- Previous solid organ transplant

- Recipient of HLA-identical kidney allograft transplant

- Recipient of an ABO incompatible donor kidney

- Known HIV infection or other major infection

- History of malignancy within 3 years (excluding treated basal cell or squamous cell

carcinoma of the skin) prior to enrollment

- History of tuberculosis

- Recipient with cardiovascular disease

- Treatment with immunosuppressive medications within 1 month prior to enrollment

- Known or suspected allergy to mice

- Pregnant or lactating

- Unable or unwilling to participate in all required study activities for the duration

of the study (6 months)

Locations and Contacts

University of Colorado Denver, Aurora, Colorado 80045, United States

University of Kentucky, Lexington, Kentucky 40536, United States

University of Michigan, Ann Arbor, Michigan 48109, United States

St Barnabas Medical Center, Livingston, New Jersey 07039, United States

Montefiore Medical Center, Bronx, New York 10467, United States

Buffalo General Hospital, Buffalo, New York 14203, United States

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States

Medical University of South Carolina, Charleston, South Carolina 29425, United States

Baylor University Medical Center, Dallas, Texas 75246, United States

Baylor All Saints, Fort Worth, Texas 76104, United States

University of Utah, Salt Lake City, Utah 84132, United States

University of Virginia Health System, Charlottesville, Virginia 22908, United States

Additional Information

Starting date: July 2010
Last updated: June 10, 2013

Page last updated: August 20, 2015

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