End Stage Renal DiseasePhase 1/2NCT01154387
Evaluating Safety and Efficacy of TOL101 Induction Versus Anti-Thymocyte Globulin to Prevent Kidney Transplant Rejection
A Phase 1/2 study testing Anti-Thymocyte Globulin, TOL101 and Steroids in people with End Stage Renal Disease and Renal Transplant, run by Tolera Therapeutics, Inc at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- End Stage Renal Disease, Renal Transplant
- What is being tested?
- Anti-Thymocyte Globulin, TOL101 and Steroids
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 12 sitesUnited States
- Study dates
- Jul 2010to Jun 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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%
Who cannot join
- 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
Show all 11Show fewer
- 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 locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Denver
Aurora, Colorado, 80045
Buffalo General Hospital
Buffalo, New York, 14203
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Health System
Charlottesville, Virginia, 22908
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75246
Baylor All Saints
Fort Worth, Texas, 76104
University of Kentucky
Lexington, Kentucky, 40536
St Barnabas Medical Center
Livingston, New Jersey, 07039
University of Utah
Salt Lake City, Utah, 84132
Montefiore Medical Center
The Bronx, New York, 10467
About this study
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
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.
- Conditions
- End Stage Renal Disease, Renal Transplant
- Being tested
- Anti-Thymocyte Globulin, TOL101, Steroids, Tacrolimus, Mycophenolate mofetil (MMF)
- Keywords
- Kidney, Renal, Transplant, Kidney Transplant, Kidney Failure, Induction, Monoclonal, Antibody, T cell, Anti-rejection, Immunosuppression
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-Thymocyte GlobulinDrug
Also called 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
TOL101Drug
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
TOL101Drug
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
SteroidsDrug
IV methylprednisolone prior to first 3 doses of study drug; oral prednisone tapered to 5-10 mg over 6 months
TacrolimusDrug
Oral administration started by 6 days post-transplantation and continued for 6 months
Mycophenolate mofetil (MMF)Drug
Oral administration started by Day 1 post-transplantation and continued for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Anti-Thymocyte Globulin | Active comparator | Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus. Receives: Drug: Anti-Thymocyte Globulin; Drug: Steroids; Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF) |
| TOL101 (Dose A) | Experimental | TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus. Receives: Drug: TOL101; Drug: Steroids; Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF) |
| TOL101 (Dose B) | Experimental | TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus. Receives: Drug: TOL101; Drug: Steroids; Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: 6 months
Secondary outcomes (9)
The effects of ascending doses of TOL101 on CD3+ T lymphocyte numbers and other immune cell subsets
Measured: 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
Measured: 14 days post-transplant
Biopsy-proven acute organ rejection
Measured: 6 months
Graft survival
Measured: 6 months
Patient survival
Measured: 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
Measured: 6 months
Delayed graft function
Measured: first 7 days post-transplant
Immunogenicity of TOL101 by measurement of anti-TOL101 antibodies
Measured: at 14 and 28 days post-transplant
The presence of Donor Specific Antibody at 3 months (Part B only) and 6 months post-transplant
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2010 (estimated)
- Study startJul 2010
- Primary completionJun 2013 (estimated)
- Study completionJun 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tolera Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stuart Flechner, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01154387
- Sponsor's protocol ID
- TTI-121
- Status last verified
- Jun 2013
- First submitted
- 26 Jun 2010
- Last updated
- 11 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01154387
- Acronym / sponsor ID
- TTI-121
- Conditions
- End Stage Renal Disease, Renal Transplant
- Keywords
- Kidney, Renal, Transplant, Kidney Transplant, Kidney Failure, Induction, Monoclonal, Antibody
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Tolera Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- Jul 2010
- Primary completion
- Jun 2013 (estimated)
- Study completion
- Jun 2013 (estimated)
- First posted
- 30 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anti-Thymocyte Globulin | Active comparator | Drug: Anti-Thymocyte Globulin, Drug: Steroids, Drug: Tacrolimus, Drug: Mycophenolate mofetil (MMF)Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus. |
| TOL101 (Dose A) | Experimental | Drug: TOL101, Drug: Steroids, Drug: Tacrolimus, Drug: Mycophenolate mofetil (MMF)TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus. |
| TOL101 (Dose B) | Experimental | Drug: TOL101, Drug: Steroids, Drug: Tacrolimus, Drug: Mycophenolate mofetil (MMF)TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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%
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-Thymocyte GlobulinAlso: Thymoglobulin1.5mg/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 | Drug | Anti-Thymocyte Globulin |
| TOL101Potential 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 | TOL101 (Dose A) |
| TOL101Potential 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 | TOL101 (Dose B) |
| SteroidsIV methylprednisolone prior to first 3 doses of study drug; oral prednisone tapered to 5-10 mg over 6 months | Drug | Anti-Thymocyte Globulin, TOL101 (Dose A), TOL101 (Dose B) |
| TacrolimusOral administration started by 6 days post-transplantation and continued for 6 months | Drug | Anti-Thymocyte Globulin, TOL101 (Dose A), TOL101 (Dose B) |
| Mycophenolate mofetil (MMF)Oral administration started by Day 1 post-transplantation and continued for 6 months | Drug | Anti-Thymocyte Globulin, TOL101 (Dose A), TOL101 (Dose B) |
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
Time frame: 6 months
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
9 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart Flechner, MD principal investigator
The Cleveland Clinic
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anti-Thymocyte Globulin, TOL101 and Steroids in people with End Stage Renal Disease and Renal Transplant, run by Tolera Therapeutics, Inc at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2013.