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

NCT ID: NCT01154387

Last Updated: 2013-06-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

85 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2013-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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End Stage Renal Disease Renal Transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Anti-Thymocyte Globulin

Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.

Group Type ACTIVE_COMPARATOR

Anti-Thymocyte Globulin

Intervention Type DRUG

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

Steroids

Intervention Type DRUG

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

Tacrolimus

Intervention Type DRUG

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

Mycophenolate mofetil (MMF)

Intervention Type DRUG

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

TOL101 (Dose A)

TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.

Group Type EXPERIMENTAL

TOL101

Intervention Type DRUG

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

Steroids

Intervention Type DRUG

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

Tacrolimus

Intervention Type DRUG

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

Mycophenolate mofetil (MMF)

Intervention Type DRUG

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

TOL101 (Dose B)

TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.

Group Type EXPERIMENTAL

TOL101

Intervention Type DRUG

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

Steroids

Intervention Type DRUG

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

Tacrolimus

Intervention Type DRUG

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

Mycophenolate mofetil (MMF)

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Steroids

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

Intervention Type DRUG

Tacrolimus

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

Intervention Type DRUG

Mycophenolate mofetil (MMF)

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

Intervention Type DRUG

Other Intervention Names

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Thymoglobulin

Eligibility Criteria

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Inclusion Criteria

* Recipient of a primary renal transplant from a living or standard criteria cadaveric donor
* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tolera Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stuart Flechner, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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University of Colorado Denver

Aurora, Colorado, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

St Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Buffalo General Hospital

Buffalo, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Baylor All Saints

Fort Worth, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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TTI-121

Identifier Type: -

Identifier Source: org_study_id

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