A Study of Obinutuzumab to Evaluate Safety and Tolerability in Hypersensitized Adult Participants With End Stage Renal Disease Awaiting Transplantation
Kidney Failure, Chronic
About this trial
This is an interventional treatment trial for Kidney Failure, Chronic
Eligibility Criteria
Inclusion Criteria:
- ESRD with a history of sensitizing events
- United network for organ sharing (UNOS) listed for a deceased donor kidney transplantation
- Estimated high likelihood of receiving an offer in the coming 12-18 months from screening as evidenced by: present on at least one match run for a deceased donor kidney during the past year, or calculated panel reactive antibody (cPRA) greater than or equal to (≥) 98 percent (based on revisions to allocation policy introduced in 2014)
- Female participants of childbearing potential: agreement to remain abstinent or use two adequate methods of contraception during the treatment period and for at least 18 months after the last dose of study drug
- Male participants: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least 12 months after the last dose of study drug
Exclusion Criteria:
- Incomplete recovery from recent major surgery or less than (<) 12 weeks since major surgery prior to baseline and participants planned surgery within 24 weeks of baseline except for kidney transplantation
- Pregnant or lactating women
- Positive serum human chorionic gonadotropin (hCG) measured at screening unless considered not clinically significant based on best medical judgement and if reassessment after ≥48 hours shows a less than a 2-fold rise from previous level
- Primary or secondary immunodeficiency disease
- Seropositivity for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) or seropositivity for Hepatitis C
- History of active or latent tuberculosis (TB) or suspicion of active TB
- Known active infection of any kind or any major episode of infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks of baseline or completion of oral anti-infective agents within 2 weeks prior to baseline
- Currently active alcohol or drug abuse or history of alcohol or drug abuse
- Participants with a history of prior kidney transplantation(s) after 6 participants with prior kidney transplants will be enrolled in the study
- Participants on peritoneal dialysis with a history of peritoneal infection at any time during the 12 weeks from prior to screening
- Participants on peritoneal dialysis with a positive culture or high cell count numbers on peritoneal fluid indicative of confirmed or suspected infection at the time of screening.
- Participants for synchronous organ transplant
- Recipients of any live attenuated vaccine(s) within 1 month of the screening visit
- Abnormal screening laboratory results
- Participants with a history of major cardiovascular or pulmonary disease
- Use of investigational agents within 12 weeks or five half-lives of randomization
- Use of an anti-CD20 therapy within the past 12 months
- Known contraindications to obinutuzumab
- History of severe allergic or anaphylactic reactions to monoclonal antibodies or components of obinutuzumab infusion
Sites / Locations
- Cedars-Sinai Medical Center
- UCSF
- Stanford Health Care
- Johns Hopkins Hospital
- Mayo Clinic - Minnesota
- Mayo Clinic
- The Christ Hospital
- University of Cincinnati College of Medicine
- University of Wisconsin
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1: Single Dose Obinutuzumab
Cohort 2: Repeated Dose Obinutuzumab
Desensitization period: Participants will receive obinutuzumab on Day 1 followed by high dose intravenous immunoglobulin (IVIG) on Days 22 and 43 of treatment period. Transplantation period: Participants who are found to qualify for transplantation and receive a compatible kidney offer after inclusion will receive two additional infusions of obinutuzumab (one at the time of transplantation [within the first 48 hours of the transplantation] and second at Week 24 post-transplantation).
Desensitization period: Participants will receive obinutuzumab on Days 1 and 15 followed by high dose IVIG on Days 22 and 43. An additional dose of obinutuzumab may be administered on Day 169 at investigator's discretion. Transplantation period: Participants who are found to qualify for transplantation and receive a compatible kidney offer after inclusion will receive two additional infusions of obinutuzumab (one at the time of transplantation [within the first 48 hours of the transplantation] and second at Week 24 post-transplantation).