Evaluating Safety and Efficacy of TOL101 Induction Versus Anti-Thymocyte Globulin to Prevent Kidney Transplant Rejection
This study is currently recruiting participants.
Verified September 2011 by Tolera Therapeutics, Inc
Sponsor:
Tolera Therapeutics, Inc
Information provided by (Responsible Party):
Tolera Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT01154387
First received: June 26, 2010
Last updated: September 21, 2011
Last verified: September 2011
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
End Stage Renal Disease Renal Transplant |
Drug: Anti-Thymocyte Globulin Drug: TOL101 Drug: Steroids Drug: Tacrolimus Drug: Mycophenolate mofetil (MMF) |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Drug Information available for:
Mycophenolic acid
Mycophenolate sodium
Tacrolimus
Mycophenolate mofetil hydrochloride
Mycophenolate mofetil
Antilymphocyte Serum
U.S. FDA Resources
Further study details as provided by Tolera Therapeutics, Inc:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]The following safety parameters will be monitored: Adverse events, standard laboratory safety evaluations (hematology and serum chemistries), symptom constellation indicating cytokine release syndrome, serum concentrations of cytokines and nitric oxide, malignancies, CMV viremia, BKV viremia, EBV viremia and other infections
Secondary Outcome Measures:
- 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) ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Biopsy-proven acute organ rejection [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Graft survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Patient survival [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- Delayed graft function [ Time Frame: first 7 days post-transplant ] [ Designated as safety issue: No ]
- Immunogenicity of TOL101 by measurement of anti-TOL101 antibodies [ Time Frame: at 14 and 28 days post-transplant ] [ Designated as safety issue: No ]
- The presence of Donor Specific Antibody at 3 months (Part B only) and 6 months post-transplant [ Time Frame: 6 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 85 |
| Study Start Date: | July 2010 |
| Estimated Study Completion Date: | January 2012 |
| Estimated Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Anti-Thymocyte Globulin
Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
|
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
Other Name: Thymoglobulin
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
|
|
Experimental: TOL101 (Dose A)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
|
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: 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
|
|
Experimental: TOL101 (Dose B)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
|
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
|
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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)
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01154387
Contacts
| Contact: Leslie O'Toole, RN | 269-585-2100 ext 2111 | lotoole@tolera.com |
Locations
| United States, Colorado | |
| University of Colorado Denver | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| United States, Kentucky | |
| University of Kentucky | Recruiting |
| Lexington, Kentucky, United States, 40536 | |
| United States, Michigan | |
| University of Michigan | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, New Jersey | |
| St Barnabas Medical Center | Recruiting |
| Livingston, New Jersey, United States, 07039 | |
| United States, New York | |
| Montefiore Medical Center | Recruiting |
| Bronx, New York, United States, 10467 | |
| Buffalo General Hospital | Recruiting |
| Buffalo, New York, United States, 14203 | |
| United States, Ohio | |
| Cleveland Clinic Foundation | Recruiting |
| Cleveland, Ohio, United States, 44195 | |
| United States, South Carolina | |
| Medical University of South Carolina | Recruiting |
| Charleston, South Carolina, United States, 29425 | |
| United States, Texas | |
| Baylor University Medical Center | Recruiting |
| Dallas, Texas, United States, 75246 | |
| Baylor All Saints | Recruiting |
| Fort Worth, Texas, United States, 76104 | |
| United States, Utah | |
| University of Utah | Recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| United States, Virginia | |
| University of Virginia Health System | Recruiting |
| Charlottesville, Virginia, United States, 22908 | |
Sponsors and Collaborators
Tolera Therapeutics, Inc
Investigators
| Principal Investigator: | Stuart Flechner, MD | The Cleveland Clinic |
More Information
No publications provided
| Responsible Party: | Tolera Therapeutics, Inc |
| ClinicalTrials.gov Identifier: | NCT01154387 History of Changes |
| Other Study ID Numbers: | TTI-121 |
| Study First Received: | June 26, 2010 |
| Last Updated: | September 21, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Tolera Therapeutics, Inc:
|
Kidney Renal Transplant Kidney Transplant Kidney Failure Induction |
Monoclonal Antibody T cell Anti-rejection Immunosuppression |
Additional relevant MeSH terms:
|
Kidney Diseases Kidney Failure, Chronic Urologic Diseases Renal Insufficiency, Chronic Renal Insufficiency Antilymphocyte Serum Mycophenolate mofetil Tacrolimus Mycophenolic Acid |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013