Safety and Efficacy of BiTE in Desensitization Therapy for Highly Sensitized Kidney Transplant Candidates With cPRA ≥ 90%

NCT07689149 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: WestChina-BITE-KT
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a prospective, open-label, two-arm exploratory clinical trial aimed at evaluating the safety and efficacy of Bispecific T-cell Engager (BiTE) therapies in refractory, highly sensitized kidney transplant candidates. Patients with end-stage renal disease (ESRD) who have a calculated panel reactive antibody (cPRA) ≥ 90% and have waited for a transplant for over 5 years, despite receiving standard desensitization therapies (e.g., IVIG, plasmapheresis, rituximab), will be enrolled. A total of 20 participants will be randomized in a 1:1 ratio to receive either Blinatumomab (a CD19×CD3 BiTE) or Teclistamab (a BCMA×CD3 BiTE). The primary objective is to evaluate the desensitization response rate, defined as the reduction of cPRA to \< 20% or by ≥ 50% from baseline, assessed at multiple time points up to 1 year post-treatment. Secondary objectives include assessing the safety profile (such as the incidence of Cytokine Release Syndrome \[CRS\] and neurotoxicity), the extent of CD19+ B cell depletion, and the proportion of participants who successfully undergo kidney transplantation within 1 year.

Conditions

HLA Sensitization; Kidney Transplantation Recipients

Keywords

Bispecific T-cell Engager; Desensitization; Kidney Transplantation; HLA Antibodies

Outcome Measures

Primary Outcomes (1)

• Percentage of participants achieving the predefined composite desensitization response

  A composite desensitization response is defined as meeting at least one of the following criteria: 1. cPRA decreases to \<20%; 2. cPRA decreases by ≥50% from baseline; 3. a previously positive HLA antibody becomes negative, defined as an MFI \<1,000; or 4. the MFI of a persistent HLA antibody decreases by ≥50% from baseline or reaches the prespecified threshold. The number and percentage of participants achieving the composite response will be reported at Months 1, 2, 3, 6, and 12 after treatment. (HLA class I and II antibodies and their mean fluorescence intensity will be assessed using a single-antigen bead assay. Calculated panel-reactive antibody levels will be determined based on the unacceptable HLA antigen profile. At each prespecified assessment timepoint, participants will be classified as responders or nonresponders, and the percentage of responders will be reported.)

  At baseline and at 1, 2, 3, 6, and 12 months after treatment

Secondary Outcomes (16)

• Percentage reduction from baseline in calculated panel-reactive antibody level

  At baseline and at 1, 2, 3, 6, and 12 months after treatment

• Absolute change from baseline in calculated panel-reactive antibody level

  At baseline and at 1, 2, 3, 6, and 12 months after treatment

• Change from baseline in the maximum mean fluorescence intensity of unacceptable HLA class I antibodies

  At baseline and at 1, 2, 3, 6, and 12 months after treatment

• Change from baseline in the maximum mean fluorescence intensity of unacceptable HLA class II antibodies

  At baseline and at 1, 2, 3, 6, and 12 months after treatment

• Number of participants receiving kidney transplantation within 12 months after treatment

  Within 12 months after the first administration of study treatment

Study Arms (2)

Bispecific T cell engager treatment group1：Blinatumomab group

EXPERIMENTAL

BiTE (CD19 x CD3 Bispecific Antibody)

Drug: BiTE (CD19 x CD3 Bispecific Antibody)

Bispecific T cell engager treatment group2：Teclistamab group

EXPERIMENTAL

BiTE (BCMA x CD3 Bispecific Antibody)

Drug: BiTE (BCMA x CD3 Bispecific Antibody)

Interventions

BiTE (CD19 x CD3 Bispecific Antibody) DRUG

Blinatumomab is a CD19×CD3 bispecific T-cell engager (BiTE) administered via intravenous infusion. This intervention utilizes a specific low-dose, short-course exploratory regimen tailored for non-oncology kidney transplant candidates to safely deplete B cells and reduce HLA antibodies. The treatment consists of two cycles separated by a 7-day interval. In Cycle 1 (Days 1-4), patients receive a continuous infusion of 9 µg/day for 4 consecutive days, with a total target dose of 35 µg for the cycle. Following the 7-day interval, Cycle 2 (Days 12-15) is administered with the identical regimen of 9 µg/day for 4 consecutive days.

Bispecific T cell engager treatment group1：Blinatumomab group

BiTE (BCMA x CD3 Bispecific Antibody) DRUG

Teclistamab is a BCMA×CD3 bispecific T-cell engager (BiTE) administered via subcutaneous injection. To mitigate the early risk of cytokine release syndrome (CRS), this intervention employs a strictly defined step-up dosing schedule. The treatment involves two cycles separated by a 7-day interval. Cycle 1 (Days 1-2) begins with a step-up dose of 0.06 mg/kg on Day 1, followed by 0.3 mg/kg on Day 2. After the 7-day interval, Cycle 2 (Days 10-11) is initiated, during which a target dose of 1.5 mg/kg is administered on Day 10.

Bispecific T cell engager treatment group2：Teclistamab group

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 participants aged 18 to 65 years.
• Diagnosis of end-stage kidney disease and being evaluated for or awaiting kidney transplantation.
• Calculated panel-reactive antibody level (cPRA) ≥90% and a kidney transplant waiting time of ≥5 years.
• Previous treatment with a conventional desensitization regimen based on intravenous immunoglobulin and/or plasma exchange, with or without rituximab, with traceable medical records.
• Persistent cPRA ≥90% or unacceptable HLA antibodies after conventional desensitization, resulting in failure to meet the immunological criteria for kidney transplantation.
• Adequate nonrenal organ function to tolerate the study treatment, including left ventricular ejection fraction \>50%, resting oxygen saturation \>94%, AST and ALT \<3 times the upper limit of normal, total bilirubin \<34.2 μmol/L, and no active infection.
• Ability to understand the study procedures, provide written informed consent, and comply with study treatment and follow-up requirements.

You may not qualify if:

• Inability to understand or comply with the study protocol or follow-up schedule.
• Known or suspected hereditary complement deficiency.
• Clinically significant central nervous system disease, including epilepsy, psychotic disorder, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis, or cranial neuropathy requiring intervention.
• AST, ALT, or GGT \>3 times the upper limit of normal, or alkaline phosphatase or total bilirubin \>1.5 times the upper limit of normal.
• Acute myocardial infarction or unstable angina within 6 months before screening, severe cardiac arrhythmia, or New York Heart Association class III or IV heart failure.
• Uncontrolled acute or chronic disease unrelated to end-stage kidney disease that may impair tolerance to study treatment.
• Active or uncontrolled infection requiring systemic treatment.
• Human immunodeficiency virus infection or uncontrolled active hepatitis B or hepatitis C infection.
• Participation in another interventional clinical study within 3 months before screening or planned concurrent participation in another interventional study.
• Previous treatment with another T-cell engager or bispecific T-cell-redirecting therapy.
• Known severe hypersensitivity to blinatumomab, teclistamab, or any of their excipients.
• Active malignancy.
• Pregnancy, breastfeeding, or planned pregnancy during the study period.
• Previous bone marrow transplantation, hematopoietic stem cell transplantation, or solid-organ transplantation other than kidney transplantation.
• Receipt of a live vaccine within 30 days before screening or planned receipt of a live vaccine during study treatment.

Sponsors & Collaborators

• West China Hospital: lead

Related Publications (6)

• Chandramohan D, Adisa O, Patel D, Ware E, Eleti N, Agarwal G. Outcomes of Kidney Transplantation in Highly HLA-Sensitized Patients Treated with Intravenous Immuno-Globulin, Plasmapheresis and Rituximab: A Meta-Analysis. Life (Basel). 2024 Aug 10;14(8):998. doi: 10.3390/life14080998.

  PMID: 39202740 RESULT

• Anwar IJ, DeLaura IF, Gao Q, Ladowski J, Jackson AM, Kwun J, Knechtle SJ. Harnessing the B Cell Response in Kidney Transplantation - Current State and Future Directions. Front Immunol. 2022 Jun 9;13:903068. doi: 10.3389/fimmu.2022.903068. eCollection 2022.

  PMID: 35757745 RESULT

• Subklewe M, Magno G, Gebhardt C, Bucklein V, Szelinski F, Arevalo HJR, Hanel G, Dorner T, Zugmaier G, von Bergwelt-Baildon M, Skapenko A, Schulze-Koops H. Application of blinatumomab, a bispecific anti-CD3/CD19 T-cell engager, in treating severe systemic sclerosis: A case study. Eur J Cancer. 2024 Jun;204:114071. doi: 10.1016/j.ejca.2024.114071. Epub 2024 Apr 22.

  PMID: 38691878 RESULT

• Bucci L, Hagen M, Rothe T, Raimondo MG, Fagni F, Tur C, Wirsching A, Wacker J, Wilhelm A, Auger JP, Pachowsky M, Eckstein M, Alivernini S, Zoli A, Kronke G, Uderhardt S, Bozec A, D'Agostino MA, Schett G, Grieshaber-Bouyer R. Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nat Med. 2024 Jun;30(6):1593-1601. doi: 10.1038/s41591-024-02964-1. Epub 2024 Apr 26.

  PMID: 38671240 RESULT

• Leon J, Aubert O, Devriese M, Alameda F, Charbonnier S, Fourgeaud J, Blein T, Nguyen TN, Troger A, Chhun S, Roelens M, Usureau C, Gons C, Roger C, Burger C, Le Stang MB, Cotteret C, Timsit MO, Fillatreau S, Rabant M, Taupin JL, Talbot A, Suarez F, Anglicheau D, Zuber J. B-cell maturation antigen-Targeted T-cell Engager Therapy Combined with B-cell Depletion for Treatment of Refractory HLA Sensitization. Kidney Int. 2026 Jun;109(6):1148-1154. doi: 10.1016/j.kint.2026.01.020. Epub 2026 Feb 13.

  PMID: 41692345 RESULT

• Bhoj VG, Kaminski M, Zhao H, Jackson K, Wang W, Liu C, Montgomery RA, Ali N, Mangiola M, Spitzer TR, Safa K, Pattanayak V, Taj R, Chiu J, Bui TM, Sonnenberg EM, Markmann JF, Milone MC, June CH, Siegel DL, Fraietta JA, Gonzalez V, Locci M, Palmer M, Monos D, Hwang WT, Sledge T, Bridges ND, Goldstein JS, Odim J, Sweet SC, Besharatian BD, Hussain SM, Brown NK, Kamoun M, Garfall AL, Naji A. Kidney Transplantation in Two Highly Sensitized Candidates after CAR T-Cell Therapy. N Engl J Med. 2026 Jun 4;394(21):2117-2125. doi: 10.1056/NEJMoa2513428.

  PMID: 42235014 RESULT

MeSH Terms

Interventions

Dental Occlusion

Intervention Hierarchy (Ancestors)

Dentistry; Dental Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Central Study Contacts

Chenliang Xu, Master of Clinical Medicine

CONTACT

+86 17208274528; fancyplain@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: July 8, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share