COMBIVAS: A trial of rituximab versus rituximab and belimumab for time to remission in ANCA vasculitis

A randomized, double blind, controlled mechanistic study of rituximab and belimumab combination therapy in PR3 ANCA-associated vasculitis - (COMBIVAS)

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-004645-24-GB

Enrollment

Registered

2019-06-20

Start date

2018-11-09

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ANCA-associated vasculitis MedDRA version: 20.1 Level: PT Classification code 10050894 Term: Anti-neutrophil cytoplasmic antibody positive vasculitis System Organ Class: 10021428 - Immune system disorders

Interventions

Product Name: Belimumab Pharmaceutical Form: Solution for injection in pre-filled syringe INN or Proposed INN: Belimumab CAS Number: 356547-88-1

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant must be =18 of age at the time of signing the informed consent form. Participants who have: 2. Have a diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis] 3. Have PR3 ANCA positivity by ELISA at screening 4. Have active disease defined by one major or three minor disease activity items on BVAS/WG 5. Be capable of giving signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15

Exclusion criteria

Exclusion criteria: 1. MPO ANCA or anti–GBM antibody positivity by ELISA 2. Presence of pulmonary haemorrhage with hypoxia at screening 3. Estimated glomerular filtration rate (eGFR) 10mg/day (or equivalent) on average over the 30 days prior to screening

Design outcomes

Primary

Measure	Time frame
Primary end point(s): The primary endpoint will be the time to PR3 ANCA negativity (measured by ELISA).;Timepoint(s) of evaluation of this end point: ANCA samples will be taken at baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44, 52 and Months 15, 18, 21, 24 The analysis of these samples will be reported at the end of the study.;Main Objective: The purpose of this study is to test a drug called belimumab (which has been approved for use in different medical conditions to the one being studied here) in patients with active ANCA-associated vasculitis. We want to find out if giving belimumab in addition to the current standard treatment will lead to improvement of the disease. ; Secondary Objective: 1. To investigate any changes in the antibodies (proteins made in the body in response to foreign substance) that are suspected to cause the AAV in patients who receive belimumab and in patients who receive a placebo (a medication that looks the same but does not have any drug in it). 2. To investigate the changes in any white blood cell values. 3. To investigate if the addition of belimumab to the standard treatment is a more effective way to treat AAV. 4. We want to find out what effects, good or bad, the addition of belumimab to the standard treatment has on people with AAV.	—

Measure

Time frame

Primary end point(s): The primary endpoint will be the time to PR3 ANCA negativity (measured by ELISA).;Timepoint(s) of evaluation of this end point: ANCA samples will be taken at baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44, 52 and Months 15, 18, 21, 24 The analysis of these samples will be reported at the end of the study.;Main Objective: The purpose of this study is to test a drug called belimumab (which has been approved for use in different medical conditions to the one being studied here) in patients with active ANCA-associated vasculitis. We want to find out if giving belimumab in addition to the current standard treatment will lead to improvement of the disease. ; Secondary Objective: 1. To investigate any changes in the antibodies (proteins made in the body in response to foreign substance) that are suspected to cause the AAV in patients who receive belimumab and in patients who receive a placebo (a medication that looks the same but does not have any drug in it). 2. To investigate the changes in any white blood cell values. 3. To investigate if the addition of belimumab to the standard treatment is a more effective way to treat AAV. 4. We want to find out what effects, good or bad, the addition of belumimab to the standard treatment has on people with AAV.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary endpoints: 1. Proportion of subjects with PR3 negativity (ELISA) 2. Change in PR3 ANCA level 3. Proportion of participants with sustained PR3 ANCA negativity at month 24 4. Change from baseline in CD4 and CD8 T cells, B cells and NK cells (TBNK flow cytometry) in blood 5. Change from baseline in naïve, transitional, memory, activated, plasmablast and plasma cell subsets (using high sensitivity B cell flow cytometry) in blood 6. Time to clinical remission (as measured by BVAS/WG) 7. Time to first relapse (as measured by BVAS/WG or prohibited medication in those who have achieved remission) 8. Proportion of participants in sustained remission 9. Proportion of participants complete remission 10. Incidence of SAEs ; Timepoint(s) of evaluation of this end point: 1. At 3, 6, 12, 18 and 24 months 2. From baseline to Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44, 52 and Months 15, 18, 21, 24 3. Month 24 4. At 3, 12, 24 months 5. At 3, 12, 24 months 6. At Weeks 4, 8, 12, 16, 20, 24, 36, 52 and Months 15, 18, 21, 24 7. At Weeks 4, 8, 12, 16, 20, 24, 36, 52 and Months 15, 18, 21, 24 8. At Months 6, 12 and 24 9. At Months 6, 12 and 24 10. All timepoints	—

Measure

Time frame

Secondary end point(s): Secondary endpoints: 1. Proportion of subjects with PR3 negativity (ELISA) 2. Change in PR3 ANCA level 3. Proportion of participants with sustained PR3 ANCA negativity at month 24 4. Change from baseline in CD4 and CD8 T cells, B cells and NK cells (TBNK flow cytometry) in blood 5. Change from baseline in naïve, transitional, memory, activated, plasmablast and plasma cell subsets (using high sensitivity B cell flow cytometry) in blood 6. Time to clinical remission (as measured by BVAS/WG) 7. Time to first relapse (as measured by BVAS/WG or prohibited medication in those who have achieved remission) 8. Proportion of participants in sustained remission 9. Proportion of participants complete remission 10. Incidence of SAEs ; Timepoint(s) of evaluation of this end point: 1. At 3, 6, 12, 18 and 24 months 2. From baseline to Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44, 52 and Months 15, 18, 21, 24 3. Month 24 4. At 3, 12, 24 months 5. At 3, 12, 24 months 6. At Weeks 4, 8, 12, 16, 20, 24, 36, 52 and Months 15, 18, 21, 24 7. At Weeks 4, 8, 12, 16, 20, 24, 36, 52 and Months 15, 18, 21, 24 8. At Months 6, 12 and 24 9. At Months 6, 12 and 24 10. All timepoints

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Countries

United Kingdom

Contacts

Public ContactCarrie Bayliss

Cambridge University Hospitals Foundation Trust

carrie.bayliss@addenbrookes.nhs.uk01223348158

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026