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

Tolera Therapeutics

Status and phase: Unknown; Phase 2; Phase 1

Conditions: End Stage Renal Disease; Renal Transplant

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01154387

TTI-121

Details and patient eligibility

About

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.

Enrollment: 85 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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85 participants in 3 patient groups

Anti-Thymocyte Globulin

Active Comparator group

Description:

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

Treatment:

Drug: Anti-Thymocyte Globulin

Drug: Steroids

Drug: Mycophenolate mofetil (MMF)

Drug: Tacrolimus

TOL101 (Dose A)

Experimental group

Description:

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

Treatment:

Drug: TOL101

Drug: Steroids

Drug: Mycophenolate mofetil (MMF)

Drug: Tacrolimus

Drug: TOL101

TOL101 (Dose B)

Experimental group

Description:

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

Treatment:

Drug: TOL101

Drug: Steroids

Drug: Mycophenolate mofetil (MMF)

Drug: Tacrolimus

Drug: TOL101