Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-004645-24
    Sponsor's Protocol Code Number:206852
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-06-20
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-004645-24
    A.3Full title of the trial
    A randomized, double blind, controlled mechanistic study of rituximab and belimumab combination therapy in PR3 ANCA-associated vasculitis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    COMBIVAS: A trial of rituximab versus rituximab and belimumab for time to remission in ANCA vasculitis
    A.3.2Name or abbreviated title of the trial where available
    (COMBIVAS)
    A.4.1Sponsor's protocol code number206852
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCambridge University Hospitals NHS Foundation Trust and the University of Cambridge
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMedical Research Council
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportGlaxoSmithKline
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCambridge University Hospitals Foundation Trust
    B.5.2Functional name of contact pointCarrie Bayliss
    B.5.3 Address:
    B.5.3.1Street AddressCambridge Clinical Trials Unit, Box 401, Addenbrooke's Hospital, Hills Road,
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeCB2 0QQ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01223348158
    B.5.5Fax number01223 256763
    B.5.6E-mailcarrie.bayliss@addenbrookes.nhs.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBelimumab
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBelimumab
    D.3.9.1CAS number 356547-88-1
    D.3.9.3Other descriptive nameHGS1006, LymphoStat-B, monoclonal anti-BLyS, LSB, BENLYSTA
    D.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    ANCA-associated vasculitis
    E.1.1.1Medical condition in easily understood language
    An autoimmune disease in which blood vessels are inflamed by overactive defense mechanisms which usually protect against infection.
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10050894
    E.1.2Term Anti-neutrophil cytoplasmic antibody positive vasculitis
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    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.
    E.2.3Trial contains a sub-study No
    E.3Principal 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
    E.4Principal 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) <30 ml/min/1.73m2 at screening
    4. Have an acute or chronic infection at screening
    5. Have received any B cell targeted therapy within 364 days of Day 1
    6. Have received cyclophosphamide within 180 days of Day 1
    7. Have received any steroid injection between 60 days of Day 1 and 14 days of screening (e.g., intramuscular [IM], intraarticular, or IV)
    8. Have received oral prednisolone >10mg/day (or equivalent) on average over the 30 days prior to screening
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be the time to PR3 ANCA negativity (measured by ELISA).
    E.5.1.1Timepoint(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.
    E.5.2Secondary 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
    E.5.2.1Timepoint(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
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    F.4.2.2In the whole clinical trial 30
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Upon completion of the trial all participants will return to the standard of care treatment as offered by their hospital for management of their vasculitis. There are no plans for the continued provision of belimumab outside of this clinical trial.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-08-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-11-09
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 09:43:10 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA