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Rituximab and Belimumab Combination Therapy in PR3 Vasculitis (COMBIVAS)

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ClinicalTrials.gov Identifier: NCT03967925
Recruitment Status : Recruiting
First Posted : May 30, 2019
Last Update Posted : July 9, 2020
Sponsor:
Collaborators:
GlaxoSmithKline
Medical Research Council
Imperial College London
University College, London
Newcastle University
University of Glasgow
University of Cambridge
Information provided by (Responsible Party):
Rachel Jones, Cambridge University Hospitals NHS Foundation Trust

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

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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


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




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



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03967925


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
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Responsible Party: Rachel Jones, Consultant Nephrologist, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03967925    
Other Study ID Numbers: 206852
First Posted: May 30, 2019    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rachel Jones, Cambridge University Hospitals NHS Foundation Trust:
proteinase 3
Additional relevant MeSH terms:
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Granulomatosis with Polyangiitis
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Prednisolone
Rituximab
Belimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Immunosuppressive Agents