Status:
RECRUITING
Tolerance Through Mixed Chimerism (Sip-Tego)
Lead Sponsor:
Tatsuo Kawai, MD, PhD
Collaborating Sponsors:
Eledon Pharmaceuticals
ITB-Med LLC
Conditions:
Kidney Failure
Transplant Recipient (Kidney)
Eligibility:
All Genders
18-65 years
Phase:
EARLY_PHASE1
Brief Summary
This is an open-label, single-institution study to assess the safety and the efficacy of the Sip-Tego regimen for the induction of donor-specific immunologic unresponsiveness to a renal allograft. The...
Detailed Description
The conditioning regimen to be used in this protocol consists of an ordered series of procedures and treatments including thymic irradiation, low-dose cyclophosphamide, antibody administration (Sipliz...
Eligibility Criteria
Inclusion
- Recipient
- Male or female 18-65 years of age.
- Subjects with chronic kidney disease stage V (GFR\<15ml/min/1.73m2) or ESRD who are treated or imminently be treated with either hemodialysis or peritoneal dialysis.
- Candidate for a living-donor renal allograft from an HLA matched or mismatched donor
- First or second renal transplant.
- EBV Seropositive
- Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation
- Ability to understand and provide informed consent.
- Negative COVID-19 test during screening and two days prior to procedure
- Recipient
Exclusion
- ABO blood group-incompatible renal allograft
- Participant with a donor-specific antibody (DSA) within 6 months prior to transplant
- Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (\<100,000/mm3)
- Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA); or positivity for hepatitis B surface antigen.
- Untreated Infection
- Left ventricular ejection fraction \< 40% as determined by TTE or clinical evidence of heart failure.
- Forced expiratory volume FEV1 or DLCO \< 50% of predicted.
- Lactation or pregnancy.
- Patients with active cancer or those with a high risk of recurrence following the American Transplant Society
- Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as non-genetic primary focal segmental glomerulosclerosis dense deposit disease, C3 glomerulonephritis, and, atypical hemolytic uremic syndrome).
- Prior dose-limiting radiation therapy for treatment of malignant disease.
- Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen. This includes long term cigarette smoking or a family history of malignancy.
- Enrollment in other investigational drug studies within 30 days prior to enrollment.
- Abnormal (\>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT) , or any patients on chronic anticoagulation therapy.
- Allergy or sensitivity to any component of Cyclophosphamide, tacrolimus, Siplizumab, Tegoprubart, or rituximab.
- The presence of any medical condition that the investigator deems incompatible with participation in the trial. This includes a history of alcohol abuse or illicit drug use/dependence.
- Any chronic or intermittent administration of immunosuppressant medication (such as for inflammatory bowel disease or asthma)
- Subjects who have non-insulin dependent diabetes (NIDDM) without good blood glucose control (HbA1c\<8%). Subjects with severe diabetes-related complications, such as advanced retinopathy, gastroparesis, or severe neuropathy that significantly impair their ability to perform normal, independent daily activities, will also be excluded.
- Donor Inclusion Criteria:
- Male or female 18-70 years of age.
- For females of childbearing potential: a serum pregnancy test showing negative results.
- Excellent health per conventional pre-donor workup (medical and psychosocial evaluation)
- Acceptable laboratory parameters (hematology in normal or near-normal range; Liver function \<2 times the upper limit of normal, and normal creatinine).
- Negative for viral infection with HBV (HbsAg and NAT), HIV (antibody and NAT), HCV (NAT), or HTLV-1.
- Cardiac/pulmonary function within normal limits (CXR, ECG).
- Ability to understand and provide informed consent.
- Meets standard institutional criteria for bone marrow aspiration and kidney donation.
- Negative COVID-19 test during screening and two days prior to procedure
Key Trial Info
Start Date :
May 31 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2030
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT06972069
Start Date
May 31 2025
End Date
December 31 2030
Last Update
September 25 2025
Active Locations (1)
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1
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114