Overview

This trial is active, not recruiting.

Conditions end stage renal disease, renal transplant
Treatments anti-thymocyte globulin, tol101, steroids, tacrolimus, mycophenolate mofetil (mmf)
Phase phase 1/phase 2
Sponsor Tolera Therapeutics, Inc
Start date July 2010
End date June 2013
Trial size 85 participants
Trial identifier NCT01154387, TTI-121

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
anti-thymocyte globulin Thymoglobulin
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
IV methylprednisolone prior to first 3 doses of study drug; oral prednisone tapered to 5-10 mg over 6 months
tacrolimus
Oral administration started by 6 days post-transplantation and continued for 6 months
mycophenolate mofetil (mmf)
Oral administration started by Day 1 post-transplantation and continued for 6 months
(Experimental)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
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
steroids
IV methylprednisolone prior to first 3 doses of study drug; oral prednisone tapered to 5-10 mg over 6 months
tacrolimus
Oral administration started by 6 days post-transplantation and continued for 6 months
mycophenolate mofetil (mmf)
Oral administration started by Day 1 post-transplantation and continued for 6 months
(Experimental)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
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
steroids
IV methylprednisolone prior to first 3 doses of study drug; oral prednisone tapered to 5-10 mg over 6 months
tacrolimus
Oral administration started by 6 days post-transplantation and continued for 6 months
mycophenolate mofetil (mmf)
Oral administration started by Day 1 post-transplantation and continued for 6 months

Primary Outcomes

Measure
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
time frame: 6 months

Secondary Outcomes

Measure
The effects of ascending doses of TOL101 on CD3+ T lymphocyte numbers and other immune cell subsets
time frame: 14 days post-transplant (Part A); 6 months (Part B)
The pharmacokinetic (PK) profile of TOL101 in renal transplant recipients and the exposure-response (PK parameter to CD3+ T lymphocyte numbers) relationship over time
time frame: 14 days post-transplant
Biopsy-proven acute organ rejection
time frame: 6 months
Graft survival
time frame: 6 months
Patient survival
time frame: 6 months
Renal function by measured GFR at 6 months post-transplant and urine protein to creatinine ratio at 3 and 6 months post-transplant
time frame: 6 months
Delayed graft function
time frame: first 7 days post-transplant
Immunogenicity of TOL101 by measurement of anti-TOL101 antibodies
time frame: at 14 and 28 days post-transplant
The presence of Donor Specific Antibody at 3 months (Part B only) and 6 months post-transplant
time frame: 6 months

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

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)

Additional Information

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
Principal investigator Stuart Flechner, MD
Trial information was received from ClinicalTrials.gov and was last updated in June 2013.
Information provided to ClinicalTrials.gov by Tolera Therapeutics, Inc.