NCT03194321

Trial to Evaluate Safety and Tolerability of Tacrolimus Extended-Release (Astagraf XL) in Human Leukocyte Antigen (HLA) Sensitized Kidney Transplant Recipients

A Prospective, Pilot Trial to Evaluate Safety and Tolerability of Tacrolimus Extended-Release (Astagraf XL) in HLA Sensitized Kidney Transplant Recipients

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Cedars-Sinai Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to demonstrate the safety of tacrolimus extended-release in HLA sensitized (HS, defined as panel reactive antibody ≥ 30%), kidney transplant recipients after desensitization with intravenous immunoglobulin (IVIG) and rituximab (also known as ritux) +/- plasma exchange (PLEX) per the standard of care with alemtuzumab induction.

Detailed description

The study will be a single center, pilot trial. It will be an open label, single-arm, non- controlled design. All HS kidney transplant recipients with Panel Reactive Antibodies (PRA) ≥ 30%, age 18 and older, requiring desensitization may be included in the study. Initial desensitization protocol for living donor (LD) or deceased donor (DD) includes Intravenous Immunoglobulin (IVIG) 2g/kg (\>70kg max 140g) given on day 0 (split over 2 days for peritoneal dialysis patients), rituximab 375mg/m2 (rounded to the nearest 100mg vial) given on day 15, and IVIG 2g/kg (\>70kg max 140g ) given on day 30. Recipients for LD or DD who are unresponsive to IVIG/ritux (after 2 months for LD and after 6 months for DD) will require PLEX 5-7 sessions followed by IVIG 2g/kg (\>70kg max 140g) and rituximab 375mg/m2. Patients will be receiving acetaminophen, antihistamine, and steroid as premedication for all infusions. A total of 20 subjects will be enrolled in the study. Subjects will take part in the study until they are one year post-transplant. All subjects will require informed consent. At the time of screening, subjects will receive a physical exam and undergo lab testing. Alemtuzumab 30mg, will be administered subcutaneously to all subjects for induction immunosuppression immediately post-transplant. Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone. Patients will receive antimicrobial prophylaxis per Cedars-Sinai Medical Center (CSMC) protocol. Lab tests and physical exams for safety will take place according to the evaluation schedule below. Safety will be assessed by the reporting of serious adverse events. Tacrolimus trough level, complete metabolic panel, liver function panel, complete blood count with differential, Donor Specific Antibodies (DSA), and urinalysis with culture will be assessed according to the evaluation schedule below. Subjects will complete the study at one year post-transplant. Consent may be withdrawn by the study participant at any time. The investigator may also withdraw the study participant at any time if there are any safety concerns. Desensitization includes Intravenous Immunoglobulin (IVIG) 2g/kg (\>70kg max 140g) given on day 0 (split over 2 days for peritoneal dialysis patients), rituximab 375mg/m2 (rounded to the nearest 100mg vial) given on day 15, and IVIG 2g/kg (\>70kg max 140g ) given on day 30. Patients will require PLEX 5-7 sessions if they have received desensitization in the past. In this case, patients will receive PLEX daily x 5-7 sessions followed by IVIG 2g/kg (\>70kg max 140g) and rituximab 375mg/m2. Patients will be receiving acetaminophen, antihistamine, and steroid as premedication for all infusions.

Conditions

• End Stage Renal Disease

Interventions

Type	Name	Description
DRUG	Tacrolimus Extended-Release Oral Capsule	Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.

Timeline

• Start date: 2017-09-11
• Primary completion: 2020-10-27
• Completion: 2020-10-27
• First posted: 2017-06-21
• Last updated: 2022-01-19
• Results posted: 2021-12-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study