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出境医 / 临床实验 / Rituximab and Belimumab Combination Therapy in PR3 Vasculitis (COMBIVAS)

Rituximab and Belimumab Combination Therapy in PR3 Vasculitis (COMBIVAS)

Study Description
Brief Summary:
Mechanistic study to assess whether dual B-cell immunotherapy by co-administration of rituximab and belimumab will result in improvements in biological endpoints, functional outcomes and clinical status compared to rituximab with placebo.

Condition or disease Intervention/treatment Phase
ANCA Associated Vasculitis Granulomatosis With Polyangiitis Drug: Belimumab Drug: Rituximab Drug: Prednisolone Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double Blind, Controlled Mechanistic Study of Rituximab and Belimumab Combination Therapy in PR3 ANCA-associated Vasculitis
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2023
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Belimumab
Weekly 200mg SC injections of belimumab for 12 months
 Drug: Belimumab
Sub-cutaneous injection
Other Name: Benlysta

Drug: Rituximab
IV infusion 1g x 2
Other Name: Truxima

Drug: Prednisolone
20mg prednisolone tapering dose
Other Name: prednisone
Placebo Comparator: Belimumab placebo
Weekly SC injections of belimumab placebo for 12 months
 Drug: Rituximab
IV infusion 1g x 2
Other Name: Truxima

Drug: Prednisolone
20mg prednisolone tapering dose
Other Name: prednisone
Outcome Measures
Primary Outcome Measures :
  1. Time to PR3 ANCA negativity [ Time Frame: Analysed at 24 months ]
    ELISA analysis at different time points to determine when PR3 ANCA can no longer be detected


Secondary Outcome Measures :
  1. Proportion of participants with PR3 ANCA negativity [ Time Frame: 2 years ]
    Measured by ELISA at various time points

  2. Change from baseline of certain cell subsets [ Time Frame: 2 years ]
    Measured by flow cytometry at various time points

  3. Time to clinical remission [ Time Frame: 2 years ]
    Measured by BVAS/WG

  4. Incidence of serious adverse events (SAEs) [ Time Frame: 2 years ]
    Hospitalisation or serious events


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants must be 18 of age

  • Have a diagnosis of AAV (granulomatosis with polyangiitis or microscopic polyangiitis)
  • Have PR3 ANCA positivity by ELISA at screening
  • Have active disease defined by one major or three minor disease activity items on BVAS/WG
  • Be capable of giving signed informed consent

Exclusion Criteria:

  • MPO ANCA or anti-GBM antibody positivity by ELISA at screening
  • Presence of pulmonary haemorrhage with hypoxia at screening
  • Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 at screening
  • Have an acute serious or chronic infection at screening
  • Have received any B cell targeted therapy within 364 days of Day 1
  • Have received any steroid injection (e.g., intramuscular [IM], intraarticular, or IV) within 60 days of Day 1 (unless given during or 14 days before screening period)
  • Have received >1.5mg methylprednisolone (IV) between 14 days prior to screening and Day 1 (including Day 1).
  • Have received oral prednisolone >10mg/day (or equivalent) on average over the 30 days prior to screening
  • Have undetectable peripheral blood B cells at screening
  • Have IgG <400mg/dl at screening
Contacts and Locations

Locations
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United Kingdom
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Contact: Kim Mynard    01223 349350    kim.mynard@addenbrookes.nhs.uk   
Principal Investigator: Rachel Jones         
Glasgow Royal Infirmary Active, not recruiting
Glasgow, United Kingdom
Imperial College London Active, not recruiting
London, United Kingdom
Royal Free Hospital Active, not recruiting
London, United Kingdom
Royal Freemann Hospital Active, not recruiting
Newcastle, United Kingdom
Nottingham University Hospitals Active, not recruiting
Nottingham, United Kingdom
Sponsors and Collaborators
Rachel Jones
GlaxoSmithKline
Medical Research Council
Imperial College London
University College, London
Newcastle University
University of Glasgow
University of Cambridge
Tracking Information
First Submitted Date  ICMJE January 18, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date July 9, 2020
Actual Study Start Date  ICMJE February 1, 2019
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2019) 		Time to PR3 ANCA negativity [ Time Frame: Analysed at 24 months ]
ELISA analysis at different time points to determine when PR3 ANCA can no longer be detected
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • Proportion of participants with PR3 ANCA negativity [ Time Frame: 2 years ]
    Measured by ELISA at various time points
  • Change from baseline of certain cell subsets [ Time Frame: 2 years ]
    Measured by flow cytometry at various time points
  • Time to clinical remission [ Time Frame: 2 years ]
    Measured by BVAS/WG
  • Incidence of serious adverse events (SAEs) [ Time Frame: 2 years ]
    Hospitalisation or serious events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab and Belimumab Combination Therapy in PR3 Vasculitis
Official Title  ICMJE A Randomised, Double Blind, Controlled Mechanistic Study of Rituximab and Belimumab Combination Therapy in PR3 ANCA-associated Vasculitis
Brief Summary Mechanistic study to assess whether dual B-cell immunotherapy by co-administration of rituximab and belimumab will result in improvements in biological endpoints, functional outcomes and clinical status compared to rituximab with placebo.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • ANCA Associated Vasculitis
  • Granulomatosis With Polyangiitis
Intervention  ICMJE
  • Drug: Belimumab
    Sub-cutaneous injection
    Other Name: Benlysta
  • Drug: Rituximab
    IV infusion 1g x 2
    Other Name: Truxima
  • Drug: Prednisolone
    20mg prednisolone tapering dose
    Other Name: prednisone
Study Arms  ICMJE
  • Active Comparator: Belimumab
    Weekly 200mg SC injections of belimumab for 12 months
    Interventions:
    • Drug: Belimumab
    • Drug: Rituximab
    • Drug: Prednisolone
  • Placebo Comparator: Belimumab placebo
    Weekly SC injections of belimumab placebo for 12 months
    Interventions:
    • Drug: Rituximab
    • Drug: Prednisolone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2019) 		30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Participants must be 18 of age

  • Have a diagnosis of AAV (granulomatosis with polyangiitis or microscopic polyangiitis)
  • Have PR3 ANCA positivity by ELISA at screening
  • Have active disease defined by one major or three minor disease activity items on BVAS/WG
  • Be capable of giving signed informed consent

Exclusion Criteria:

  • MPO ANCA or anti-GBM antibody positivity by ELISA at screening
  • Presence of pulmonary haemorrhage with hypoxia at screening
  • Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 at screening
  • Have an acute serious or chronic infection at screening
  • Have received any B cell targeted therapy within 364 days of Day 1
  • Have received any steroid injection (e.g., intramuscular [IM], intraarticular, or IV) within 60 days of Day 1 (unless given during or 14 days before screening period)
  • Have received >1.5mg methylprednisolone (IV) between 14 days prior to screening and Day 1 (including Day 1).
  • Have received oral prednisolone >10mg/day (or equivalent) on average over the 30 days prior to screening
  • Have undetectable peripheral blood B cells at screening
  • Have IgG <400mg/dl at screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03967925
Other Study ID Numbers  ICMJE 206852
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rachel Jones, Cambridge University Hospitals NHS Foundation Trust
Study Sponsor  ICMJE Rachel Jones
Collaborators  ICMJE
  • GlaxoSmithKline
  • Medical Research Council
  • Imperial College London
  • University College, London
  • Newcastle University
  • University of Glasgow
  • University of Cambridge
Investigators  ICMJE Not Provided
PRS Account Cambridge University Hospitals NHS Foundation Trust
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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