Overview

This trial is active, not recruiting.

Condition kidney failure, chronic
Treatment obinutuzumab
Phase phase 1
Target CD20
Sponsor Hoffmann-La Roche
Start date November 2015
End date August 2018
Trial size 24 participants
Trial identifier NCT02586051, WT29749

Summary

This is a Phase Ib, open-label study of single and repeat doses of obinutuzumab administered as intravenous (IV) infusion in adults with end stage renal disease (ESRD). Participants will be enrolled into two cohorts receiving either one (Cohort 1) or two or more (Cohort 2) obinutuzumab infusions. Both cohorts will receive standard pretreatments to reduce the risk of infusion-related reactions (IRRs). In Cohort 1, 5 participants will receive single dose obinutuzumab IV infusion on Day 1. Following review of Cohort 1 aggregated safety data up to 4 weeks post dose for the last participant of cohort 1, cohort 2 will be allowed to proceed. In Cohort 2, 20 participants will receive obinutuzumab IV infusion on Days 1 and 15. Participants who qualify for transplantation and receive a compatible kidney offer after inclusion in Cohort 1 or Cohort 2 will receive two additional infusions (one at the time of transplantation and second at Week 24 post-transplantation) of obinutuzumab. Assessment of the safety and tolerability of the obinutuzumab regimen will be conducted at Week 24 of the desensitization phase and at Week 28 post-transplantation. All participants will be monitored for a minimum of 12 months following the last obinutuzumab infusion.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants will receive obinutuzumab IV infusion on Day 1 of treatment period.
obinutuzumab RO5072759
Participants will receive obinutuzumab IV infusion on Day 1 in Cohort 1 and on Days 1 and 15 and 169 (at investigator's discretion) in Cohort 2.
(Experimental)
Participants will receive obinutuzumab IV infusion on Days 1 and 15 of treatment period. An additional dose of obinutuzumab IV infusion may be administered on Day 169 at investigator's discretion.
obinutuzumab RO5072759
Participants will receive obinutuzumab IV infusion on Day 1 in Cohort 1 and on Days 1 and 15 and 169 (at investigator's discretion) in Cohort 2.

Primary Outcomes

Measure
Number of participants with adverse events
time frame: Up to Week 76 (Follow-up)

Secondary Outcomes

Measure
Maximum Observed Plasma Concentration (Cmax) of entire study
time frame: Up to Week 76 (Follow-up)
Cmax after first course of study drug (Cmax1)
time frame: Up to Week 76 (Follow-up)
Cmax after second course of study drug (Cmax2)
time frame: Up to Week 76 (Follow-up)
Area under the concentration time curve (AUC)
time frame: Up to Week 76 (Follow-up)
Systemic Clearance (CL)
time frame: Up to Week 76 (Follow-up)
Volume of Distribution at Steady State (Vss)
time frame: Up to Week 76 (Follow-up)
Half-life (t1/2)
time frame: Up to Week 76 (Follow-up)

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - ESRD with a history of sensitizing events - United network for organ sharing (UNOS)-listed with at least one match run for a deceased donor kidney during the past year - Adult participants with 18 to 65 years of age - 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 prior to the first obinutuzumab infusion - 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 who received more than one organ transplant - 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 - Participants with ESRD on peritoneal dialysis

Additional Information

Official title A Phase Ib, Single- and Multiple-Dose, Open-Label Study of The Safety, Pharmacokinetics and Pharmacodynamics of Obinutuzumab in Adults With End-Stage Renal Disease and Hypersensitization Awaiting Renal Transplantation
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.