A Study of Obinutuzumab to Evaluate Safety and Tolerability in Hypersensitized Adult Participants With End Stage Renal Disease Awaiting Transplantation

NCT02586051 | Completed Phase 1 FDA Drug

• 1 other identifier: WT29749
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 9

Brief 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). Desensitization Period: In Cohort 1, 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, participants will receive obinutuzumab IV infusion on Days 1 and 15. Transplantation Period: 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.

Conditions

Kidney Failure, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Adverse Events

  Week 0 up to Week 24 of the desensitization phase

Secondary Outcomes (7)

• Maximum Serum Concentration (Cmax) of Obinutuzumab During the Entire Study

  Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

• Cmax of Obinutuzumab After the First Course of Obinutuzumab (Cmax1)

  Baseline up to Week 2 (detailed timeframe is given in outcome measure description)

• Cmax of Obinutuzumab After the Second Course of Obinutuzumab (Cmax2)

  Cohort 2: Pre-dose (0 hr), within 1 hour of the end of infusion, at 24 hours post-start of infusion at Week 2 Duration of infusion: approximately 3.5 hr.

• Area Under the Concentration Time Curve (AUC) of Obinutuzumab

  Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

• Systemic Clearance (CL) of Obinutuzumab

  Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Study Arms (2)

Cohort 1: Single Dose Obinutuzumab

EXPERIMENTAL

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).

Drug: Obinutuzumab; Drug: Intravenous Immunoglobulin

Cohort 2: Repeated Dose Obinutuzumab

EXPERIMENTAL

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).

Drug: Obinutuzumab; Drug: Intravenous Immunoglobulin

Interventions

Obinutuzumab DRUG

Obinutuzumab 1000 milligrams (mg) IV infusion.

Also known as: RO5072759

Cohort 1: Single Dose Obinutuzumab; Cohort 2: Repeated Dose Obinutuzumab

Intravenous Immunoglobulin DRUG

High dose (2 grams per kilogram \[g/kg\]) IVIG (maximum 140 grams).

Cohort 1: Single Dose Obinutuzumab; Cohort 2: Repeated Dose Obinutuzumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCSF

San Francisco, California, 94115, United States

Location

Stanford Health Care

Stanford, California, 94305, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic - Minnesota

Rochester, Minnesota, 55905, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45219, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Redfield RR, Jordan SC, Busque S, Vincenti F, Woodle ES, Desai N, Reed EF, Tremblay S, Zachary AA, Vo AA, Formica R, Schindler T, Tran H, Looney C, Jamois C, Green C, Morimoto A, Rajwanshi R, Schroeder A, Cascino MD, Brunetta P, Borie D. Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant. Am J Transplant. 2019 Nov;19(11):3035-3045. doi: 10.1111/ajt.15514. Epub 2019 Jul 23.

  PMID: 31257724 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

obinutuzumab; Immunoglobulins, Intravenous

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

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 26, 2015
• Study Start: November 19, 2015
• Primary Completion: November 26, 2018
• Study Completion: November 26, 2018
• Last Updated: January 29, 2020

Record last verified: 2020-01

Locations

US (9)