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

27. ledna 2020 aktualizováno: Hoffmann-La Roche

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

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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

24

Fáze

  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Spojené státy
    • California
      • Los Angeles, California, Spojené státy, 90048
        • Cedars-Sinai Medical Center
      • San Francisco, California, Spojené státy, 94115
        • UCSF
      • Stanford, California, Spojené státy, 94305
        • Stanford Health Care
    • Maryland
      • Baltimore, Maryland, Spojené státy, 21287
        • Johns Hopkins Hospital
    • Minnesota
      • Rochester, Minnesota, Spojené státy, 55905
        • Mayo Clinic
      • Rochester, Minnesota, Spojené státy, 55905
        • Mayo Clinic - Minnesota
    • Ohio
      • Cincinnati, Ohio, Spojené státy, 45219
        • The Christ Hospital
      • Cincinnati, Ohio, Spojené státy, 45219
        • University of Cincinnati College of Medicine
    • Wisconsin
      • Madison, Wisconsin, Spojené státy, 53792
        • University of Wisconsin

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 65 let (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Nerandomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Cohort 1: Single 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).
Lék: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) IV infusion.
Ostatní jména:
  • RO5072759
Lék: Intravenous Immunoglobulin
High dose (2 grams per kilogram [g/kg]) IVIG (maximum 140 grams).
Experimentální: Cohort 2: Repeated Dose Obinutuzumab

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).
Lék: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) IV infusion.
Ostatní jména:
  • RO5072759
Lék: Intravenous Immunoglobulin
High dose (2 grams per kilogram [g/kg]) IVIG (maximum 140 grams).

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Časové okno
Percentage of Participants with Adverse Events
Časové okno: Week 0 up to Week 24 of the desensitization phase
Week 0 up to Week 24 of the desensitization phase

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Maximum Serum Concentration (Cmax) of Obinutuzumab During the Entire Study
Časové okno: Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Detailed timeframe:

Cohort 1: Pre-dose (0 hour [hr]); within 1 hr of end of infusion; at 24 hr post-start of infusion at Day 1; Weeks 3 and 6 (immediately prior to IVIG administration); at Weeks 1, 2, 12, 24, 36 and 52; early termination and long-term follow up visit (up to Week 76).

Cohort 2: Pre-dose (0 hr), within 1 hr of end of infusion, at 24 hr post-start of infusion at Week 0 and Week 2; immediately prior to IVIG administration at Week 3 and 6; Weeks 24 (pre-dose [0 hr] and within 1 hr of end of infusion if optional third infusion is provided); additionally at Weeks 1, 12, 36; and 52; at early termination and long-term follow-up visit (up to Week 76).

Transplantation Period (Cohorts 1 and 2) (for participants undergoing transplantation): Pre-dose (0-30 minutes) and within 1 hr of end of infusion for each obinutuzumab dose at Weeks 0 and 24), at long-term follow-up visit (Week 76). Duration of infusion: approximately 4.5 hr for 1st infusion, and 3.5 hr for subsequent infusions.
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)
Časové okno: Baseline up to Week 2 (detailed timeframe is given in outcome measure description)
Cohort 1: Pre-dose (0 hr); within 1 hr of the end of infusion; at 24 hr post-start of infusion at Day 1; at Weeks 1, 2 Cohort 2: Pre-dose (0 hr), within 1 hour of the end of infusion, at 24 hours post-start of infusion at Week 0; Pre-dose (0 hr) at Week 2 Duration of infusion: approximately 4.5 hr.
Baseline up to Week 2 (detailed timeframe is given in outcome measure description)
Cmax of Obinutuzumab After the Second Course of Obinutuzumab (Cmax2)
Časové okno: 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.
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
Časové okno: Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Detailed timeframe:

Cohort 1: Pre-dose (0 hr); within 1 hr of end of infusion; at 24 hr post-start of infusion at Day 1; Weeks 3 and 6 (immediately prior to IVIG administration); at Weeks 1, 2, 12, 24, 36 and 52; early termination and long-term follow up visit (up to Week 76).

Cohort 2: Pre-dose (0 hr), within 1 hr of end of infusion, at 24 hr post-start of infusion at Week 0 and Week 2; immediately prior to IVIG administration at Week 3 and 6; Weeks 24 (pre-dose [0 hr] and within 1 hr of end of infusion if optional third infusion is provided); additionally at Weeks 1, 12, 36; and 52; at early termination and long-term follow-up visit (up to Week 76).

Transplantation Period (Cohorts 1 and 2) (for participants undergoing transplantation): Pre-dose (0-30 minutes) and within 1 hr of end of infusion for each obinutuzumab dose at Weeks 0 and 24), at long-term follow-up visit (Week 76). Duration of infusion: approximately 4.5 hr for 1st infusion, and 3.5 hr for subsequent infusions.
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
Časové okno: Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Detailed timeframe:

Cohort 1: Pre-dose (0 hr); within 1 hr of end of infusion; at 24 hr post-start of infusion at Day 1; Weeks 3 and 6 (immediately prior to IVIG administration); at Weeks 1, 2, 12, 24, 36 and 52; early termination and long-term follow up visit (up to Week 76).

Cohort 2: Pre-dose (0 hr), within 1 hr of end of infusion, at 24 hr post-start of infusion at Week 0 and Week 2; immediately prior to IVIG administration at Week 3 and 6; Weeks 24 (pre-dose [0 hr] and within 1 hr of end of infusion if optional third infusion is provided); additionally at Weeks 1, 12, 36; and 52; at early termination and long-term follow-up visit (up to Week 76).

Transplantation Period (Cohorts 1 and 2) (for participants undergoing transplantation): Pre-dose (0-30 minutes) and within 1 hr of end of infusion for each obinutuzumab dose at Weeks 0 and 24), at long-term follow-up visit (Week 76). Duration of infusion: approximately 4.5 hr for 1st infusion, and 3.5 hr for subsequent infusions.
Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)
Volume of Distribution at Steady State (Vss) of Obinutuzumab
Časové okno: Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Detailed timeframe:

Cohort 1: Pre-dose (0 hr); within 1 hr of end of infusion; at 24 hr post-start of infusion at Day 1; Weeks 3 and 6 (immediately prior to IVIG administration); at Weeks 1, 2, 12, 24, 36 and 52; early termination and long-term follow up visit (up to Week 76).

Cohort 2: Pre-dose (0 hr), within 1 hr of end of infusion, at 24 hr post-start of infusion at Week 0 and Week 2; immediately prior to IVIG administration at Week 3 and 6; Weeks 24 (pre-dose [0 hr] and within 1 hr of end of infusion if optional third infusion is provided); additionally at Weeks 1, 12, 36; and 52; at early termination and long-term follow-up visit (up to Week 76).

Transplantation Period (Cohorts 1 and 2) (for participants undergoing transplantation): Pre-dose (0-30 minutes) and within 1 hr of end of infusion for each obinutuzumab dose at Weeks 0 and 24), at long-term follow-up visit (Week 76). Duration of infusion: approximately 4.5 hr for 1st infusion, and 3.5 hr for subsequent infusions.
Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)
Half-life (t1/2) of Obinutuzumab
Časové okno: Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Detailed timeframe:

Cohort 1: Pre-dose (0 hr); within 1 hr of end of infusion; at 24 hr post-start of infusion at Day 1; Weeks 3 and 6 (immediately prior to IVIG administration); at Weeks 1, 2, 12, 24, 36 and 52; early termination and long-term follow up visit (up to Week 76).

Cohort 2: Pre-dose (0 hr), within 1 hr of end of infusion, at 24 hr post-start of infusion at Week 0 and Week 2; immediately prior to IVIG administration at Week 3 and 6; Weeks 24 (pre-dose [0 hr] and within 1 hr of end of infusion if optional third infusion is provided); additionally at Weeks 1, 12, 36; and 52; at early termination and long-term follow-up visit (up to Week 76).

Transplantation Period (Cohorts 1 and 2) (for participants undergoing transplantation): Pre-dose (0-30 minutes) and within 1 hr of end of infusion for each obinutuzumab dose at Weeks 0 and 24), at long-term follow-up visit (Week 76). Duration of infusion: approximately 4.5 hr for 1st infusion, and 3.5 hr for subsequent infusions.
Baseline up to last follow up (up to 76 weeks post-transplantation) (detailed timeframe is given in outcome measure description)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Hoffmann-La Roche

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

19. listopadu 2015

Primární dokončení (Aktuální)

26. listopadu 2018

Dokončení studie (Aktuální)

26. listopadu 2018

Termíny zápisu do studia

První předloženo

23. října 2015

První předloženo, které splnilo kritéria kontroly kvality

23. října 2015

První zveřejněno (Odhad)

26. října 2015

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

29. ledna 2020

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

27. ledna 2020

Naposledy ověřeno

1. ledna 2020

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • WT29749

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

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