Tolerance Through Mixed Chimerism (Sip-Tego)

NCT ID: NCT06972069

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-31
• Study Completion Date: 2030-12-31

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Recipient

Recipient of kidney and bone marrow transplant

Group Type: EXPERIMENTAL

Combined Kidney/Bone Marrow Transplant

Intervention Type: 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.

Conditioning Regimen (Rituxan, Siplizumab, Cyclophosphamide, Tegoprubart)

Intervention Type: 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).

Donor

Living donors of kidney and bone marrow transplant

Group Type: OTHER

Donation of Kidney / Bone Marrow

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female 18-65 years of age.

2. 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.

3. Candidate for a living-donor renal allograft from an HLA matched or mismatched donor

4. First or second renal transplant.

5. EBV Seropositive

6. 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

7. Ability to understand and provide informed consent.

8. Negative COVID-19 test during screening and two days prior to procedure

1. Male or female 18-70 years of age.

2. For females of childbearing potential: a serum pregnancy test showing negative results.

3. Excellent health per conventional pre-donor workup (medical and psychosocial evaluation)

4. Acceptable laboratory parameters (hematology in normal or near-normal range; Liver function <2 times the upper limit of normal, and normal creatinine).

5. Negative for viral infection with HBV (HbsAg and NAT), HIV (antibody and NAT), HCV (NAT), or HTLV-1.

6. Cardiac/pulmonary function within normal limits (CXR, ECG).

7. Ability to understand and provide informed consent.

8. Meets standard institutional criteria for bone marrow aspiration and kidney donation.

9. Negative COVID-19 test during screening and two days prior to procedure

Exclusion Criteria

1. ABO blood group-incompatible renal allograft

2. Participant with a donor-specific antibody (DSA) within 6 months prior to transplant

3. Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (<100,000/mm3)

4. 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.

5. Untreated Infection

6. Left ventricular ejection fraction < 40% as determined by TTE or clinical evidence of heart failure.

7. Forced expiratory volume FEV1 or DLCO < 50% of predicted.

8. Lactation or pregnancy.

9. Patients with active cancer or those with a high risk of recurrence following the American Transplant Society

10. 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).

11. Prior dose-limiting radiation therapy for treatment of malignant disease.

12. 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.

13. Enrollment in other investigational drug studies within 30 days prior to enrollment.

14. 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.

15. Allergy or sensitivity to any component of Cyclophosphamide, tacrolimus, Siplizumab, Tegoprubart, or rituximab.

16. 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.

17. Any chronic or intermittent administration of immunosuppressant medication (such as for inflammatory bowel disease or asthma)

18. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eledon Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

ITB-Med LLC

INDUSTRY

Sponsor Role: collaborator

Tatsuo Kawai, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Tatsuo Kawai, MD, PhD

Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Tatsuo Kawai, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator / Transplant Surgeon

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kerry Augusta, RN

Role: CONTACT

kaugusta@mgb.org

617-724-8570

Facility Contacts

Kerry Augusta, RN

Role: primary

kaugusta@mgh.harvard.edu

617-724-8570

Related Links

https://www.massgeneral.org/transplant/transplant-programs/tolerance

Related Info

Other Identifiers

2025P000818

Identifier Type: -

Identifier Source: org_study_id