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

NCT03194321 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: Pro00043132
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

End Stage Renal Disease

Keywords

Highly-sensitized; Kidney transplantation; Desensitization

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events and Treatment Failure

  To determine the safety of tacrolimus extended-release in HS kidney transplant recipients after desensitization with intravenous immunoglobulin (IVIG) and rituximab +/- plasma exchange (PLEX) per the standard of care and alemtuzumab induction. This will be measured by the rate of serious adverse events (SAEs) and treatment failure. Treatment failure is defined as a composite of biopsy proven acute rejection (BPAR), graft failure, or death. BPAR is defined as ≥ Banff 1A using the Banff 2007 criteria.

  12 months

Secondary Outcomes (2)

• Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)

  Transplant, 1 month, 3 months, 6 months, 9 months, and 12 months

• Tolerability as Defined by the Number of Subjects Discontinuing the Study Medication

  12 months

Study Arms (1)

Tacrolimus Extended-Release Arm

EXPERIMENTAL

All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.

Drug: Tacrolimus Extended-Release Oral Capsule

Interventions

Tacrolimus Extended-Release Oral Capsule DRUG

Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.

Tacrolimus Extended-Release Arm

Eligibility Criteria

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

You may qualify if:

• Recipient of a deceased or living donor kidney allograft
• Patients must have undergone desensitization with intravenous immunoglobulin (IVIG) and rituximab with or without plasma exchange prior to transplant or be administered IVIG and rituximab peri-operatively (within seven days of transplant) post-transplant
• Age 18 and over
• Able to understand and provide informed consent
• Calculated Panel Reactive Antibodies (CPRA)\> 30% demonstrated on 3 consecutive samples. The methodology to measure polymerase chain reaction (PCR) includes FLOW and Luminex Single Antigen Assay.
• At transplant, patient must have an acceptable crossmatch (as defined as T-or B- Flow Cytometry Crossmatch (FCMX) ≤ 225 MCS) from non-HLA identical donor. Negative crossmatch is Tpronase FCMX \<70; T- FCMX \<50 and Bpronase FCMX \<130; B-FCMX \<100.

You may not qualify if:

• Recipients of a dual simultaneous kidney/liver, kidney/heart, kidney/lung, or kidney/pancreas transplant
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
• Patients being treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4
• Patients with a clinically significant systemic infection within 30 days prior to transplant
• Patients who have any surgical or medical condition that may affect absorption of drug, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and/or excretion of study medication
• Women of childbearing potential who are either pregnant, lactating, planning to become pregnant during this trial, or with a positive serum or urine pregnancy test. Women of childbearing potential must be willing to agree to contraceptive practices.
• Patients who are PCR positive for Hep B, Hep C, or HIV.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Small sample size; Early withdrawal of participants.

Results Point of Contact

• Title: Dr. Stanley C. Jordan, MD
• Organization: Cedars Sinai Medical Center

sjordan@cshs.org

310-423-2641

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Nephrology & Transplant Immunology

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: June 21, 2017
• Study Start: September 11, 2017
• Primary Completion: October 27, 2020
• Study Completion: October 27, 2020
• Last Updated: January 19, 2022
• Results First Posted: December 30, 2021

Record last verified: 2022-01

Locations

US (1)