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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 gennaio 2020 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

24

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 65 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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).
Droga: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) IV infusion.
Altri nomi:
  • RO5072759
Droga: Intravenous Immunoglobulin
High dose (2 grams per kilogram [g/kg]) IVIG (maximum 140 grams).
Sperimentale: 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).
Droga: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) IV infusion.
Altri nomi:
  • RO5072759
Droga: Intravenous Immunoglobulin
High dose (2 grams per kilogram [g/kg]) IVIG (maximum 140 grams).

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Percentage of Participants with Adverse Events
Lasso di tempo: Week 0 up to Week 24 of the desensitization phase
Week 0 up to Week 24 of the desensitization phase

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Maximum Serum Concentration (Cmax) of Obinutuzumab During the Entire Study
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Hoffmann-La Roche

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

19 novembre 2015

Completamento primario (Effettivo)

26 novembre 2018

Completamento dello studio (Effettivo)

26 novembre 2018

Date di iscrizione allo studio

Primo inviato

23 ottobre 2015

Primo inviato che soddisfa i criteri di controllo qualità

23 ottobre 2015

Primo Inserito (Stima)

26 ottobre 2015

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

29 gennaio 2020

Ultimo aggiornamento inviato che soddisfa i criteri QC

27 gennaio 2020

Ultimo verificato

1 gennaio 2020

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • WT29749

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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