NCT06972069

Tolerance Through Mixed Chimerism (Sip-Tego)

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Tatsuo Kawai, MD, PhD · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

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 (Siplizumab, rituximab and tegoprubart), and bone marrow cell infusion. The surgical techniques for the renal transplant will be accomplished according to the surgeon's clinical judgment and experience using standard techniques in use at the institution. The donor nephrectomy will be accomplished according to the surgeon's clinical judgment and experience. The conditioning regimen requires six days leading up to the day of transplantation, which is designated as study Day 0. Negative numbers in descending order designate days pre-transplant, while positive numbers in ascending order designate days post-transplant. Refer to Figure 2 in Section 1.2. for the schema of the conditioning regimen.

Conditions

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

Interventions

Type	Name	Description
PROCEDURE	Combined Kidney/Bone Marrow Transplant	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.
PROCEDURE	Donation of Kidney / Bone Marrow	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.
DRUG	Conditioning Regimen (Rituxan, Siplizumab, Cyclophosphamide, Tegoprubart)	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).

Timeline

• Start date: 2025-05-31
• Primary completion: 2030-12-31
• Completion: 2030-12-31
• First posted: 2025-05-14
• Last updated: 2025-09-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study