Tolerance Through Mixed Chimerism (Sip-Tego)

NCT06972069 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2025P000818
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 investigators propose to treat 6 adult subjects in end-stage renal disease (ESRD) who do not demonstrate evidence of prior sensitization.

Conditions

Kidney Failure; Transplant Recipient (Kidney); Transplant Tolerance; Immunosuppresion; Immunosuppression After Kidney Transplantation

Keywords

Tolerance; Transplant without immunosuppression; kidney transplant

Outcome Measures

Primary Outcomes (3)

• Induction of mixed chimerism without chimeric transition syndrome

  This will be measured by a chimerism level of \>0% donor chimerism at anytime post transplant, and when the level is returning to 0% chimerism there is no evidence of chimeric transition syndrome. This is defined in the protocol by any of the following The clinical symptoms of CTS include acute kidney injury with rapid deterioration of kidney function (elevated creatinine, decreased blood flow to the renal allograft by US), minor to moderate fever, fluid retention or peripheral edema.

  7 Years

• Achievement of IS minimization (tacrolimus or Belatacept monotherapy)

  This will be measured by a patient weaning and maintaining only one agent of immunosuppression (either Tacrolimus or Belatacept)

  7 Years

• Number of patients who complete full immunosuppression withdrawal

  The number (and therefore percentage) of patients who discontinue all immunosuppression (ie. completely stop Tacrolimus or Belatacept)

  7 Years

Secondary Outcomes (12)

• Participants who are alive at the end of the study

  7 Years

• Kidney Graft Survival

  7 Years

• Incidence of CTS

  7 Years

• Incidence of Acute Rejection

  7 Years

• Incidence of Donor Specific Antibody development

  7 Years

Study Arms (2)

Recipient

EXPERIMENTAL

Recipient of kidney and bone marrow transplant

Procedure: Combined Kidney/Bone Marrow Transplant; Drug: Conditioning Regimen (Rituxan, Siplizumab, Cyclophosphamide, Tegoprubart)

Donor

OTHER

Living donors of kidney and bone marrow transplant

Procedure: Donation of Kidney / Bone Marrow

Interventions

Combined Kidney/Bone Marrow Transplant PROCEDURE

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 (Siplizumab, rituximab and tegoprubart), and bone marrow cell infusion.

Recipient

Donation of Kidney / Bone Marrow PROCEDURE

The donor will undergo nephrectomy and under general anesthesia. Donors will undergo bone marrow harvested under general anesthesia. Sufficient marrow will be obtained to provide at least 2 x 108 nucleated cells per kilogram weight of the recipient.

Donor

Conditioning Regimen (Rituxan, Siplizumab, Cyclophosphamide, Tegoprubart) DRUG

Recipients will receive a conditioning regimen that includes rituximab on study day -6 and -2, Siplizumab (0.6mg/kg) on day -6, -1, 0 and +1, cyclophosphamide (CP, 22.5mg/kg) on days -5 and -4. Tegoprubart (Fc-modified anti-CD154 mAB, Eledon Pharm) 20mg/kg will be administered on days 0, 2, 5, 12 and 19).

Recipient

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tatsuo Kawai, MD, PhD: lead
• Eledon Pharmaceuticals: collaborator
• ITB-Med LLC: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Transplantation Conditioning; Rituximab; siplizumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Tatsuo Kawai, MD PhD

  Principal Investigator / Transplant Surgeon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kerry Augusta, RN

CONTACT

617-724-8570; kaugusta@mgb.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 14, 2025
• Study Start: May 31, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

US (1)