Condition category
Musculoskeletal Diseases
Date applied
28/11/2016
Date assigned
28/11/2016
Last edited
01/12/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Systemic lupus erythematosus (SLE) is a long-term (chronic) disease which causes widespread inflammation (swelling) in the body. SLE occurs when the immune system attacks the body’s own cells (autoimmune disease). A person’s genes alongside other factors such as diet have been connected with the development and progression of the disease. B cell depletion therapy (normally rituximab) is used as part of standard of care in patients where their lupus is active. B cell depletion therapy removes a type of immune cell called B cells from the body. B cells can cause disease in lupus patients. Although patients respond to B cell depletion therapy the disease can quickly return. This is likely to be because a chemical (also known as a stimulating factor) called BAFF increases in the body once treatment ends, and switches the lupus back on. Belimumab is a drug that stops BAFF from working and has been shown to work in patients with lupus. The aim of this study is to investigate the safety and effectiveness of Belimumab in treating SLE.

Who can participate?
Men and women aged between 18-75 years old with systemic lupus erythematosus (SLE).

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive Belimumab through a drip at two week intervals for the first three doses and then at four week intervals until 52 weeks. Those in the second group receive normal saline (salt water) through a drip according to the same schedule. After 52 weeks, participants in both groups provide blood samples and complete questionnaires in order to find out how effective the belimumab treatment is compared to the placebo (dummy) treatment.

What are the possible benefits and risks of participating?
The benefits of participating include study patients having a regular review of their Lupus by an experienced Lupus specialist and information collected from this study will help improve the treatment of lupus. As Belimumab has not been given after drugs like rituximab in a research study it is not known if this is a safe combination. It is also possible that the risks of cancer, infections and effects on mood (feeling anxious or depressed) could be increased when both Belimumab and rituximab are administered close together. The most common side effects that happen during or soon after a belimumab dose are nausea, diarrhoea, and fever.

Where is the study run from?
University College London Hospital (lead centre) and 14 other NHS hospitals in England (UK)

When is the study starting and how long is it expected to run for?
January 2014 to December 2019

Who is funding the study?
1. Arthritis Research UK (UK)
2. GlaxoSmithKline foundation (UK)
3. University College London Biomedical Research Centre (UK)

Who is the main contact?
1. Ms Felecia Ikeji (public)
f.ikeji@ucl.ac.uk
2. Professor Michael Ehrenstein
m.ehrenstein@ucl.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Ms Felicia Ikeji

ORCID ID

Contact details

University College London
Comprehensive Clinical Trials Unit
Gower Street
London
WC1E 6BT
United Kingdom
+44 20 7679 6163
f.ikeji@ucl.ac.uk

Type

Scientific

Additional contact

Prof Michael Ehrenstein

ORCID ID

Contact details

University College London Hospital
253 Euston Road
London
NW1 2BU
United Kingdom
+44 20 3447 9035
m.ehrenstein@ucl.ac.uk

Additional identifiers

EudraCT number

2015-005543-14

ClinicalTrials.gov number

Protocol/serial number

32235

Study information

Scientific title

Safety and efficacy of Belimumab After B cell depletion therapy in systemic LUPUS erythematosus

Acronym

BEAT LUPUS

Study hypothesis

This study aims to find out whether a drug called Belimumab when used after B cell depletion therapy is safe and effective in reducing systemic lupus erythematosus (lupus) disease activity.

Ethics approval

London - Hampstead Research Ethics Committee, 07/07/2016, ref: 16/LO/1024

Study design

Multicentre phase II randomised double blind placebo-controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Musculoskeletal disorders, Primary sub-specialty: Other; UKCRC code/ Disease: Inflammatory and Immune System/ Certain disorders involving the immune mechanism

Intervention

Participants are randomised to one of two groups.

Intervention group: Patients will recieve Belimumab according to the standard dosage regime of infusions of 10mg/kg at 2 week intervals for the first 3 doses and at 4 week intervals thereafter up until week 52.

Control group: Patients will receive the same volume of normal saline infusions (0.9% saline) at the same time points as the active treatment group.

In total the treatment period (Belimumab or placebo) will be 52 weeks, with 16 weeks of further follow up. Each patient will therefore be enrolled in the study for 68 weeks in total.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Anti dsDNA-antibody levels are measured using blood sample testing at week -4 (baseline) and 52 weeks.

Secondary outcome measures

1. Anti-dsDNA antibody levels are measured using Blood sample testing at 24 and 68 weeks
2. Proportion of patients with any adverse events is measured by reviewing patient notes, blood sample testing, SLEDAI 2000 questionnaire, SLICC index and BILAG 2004 at week -4 , week 0, week 2 and every 4 weeks until week 68
3. Proportion of patients with any infections is measured by reviewing patient notes, blood sample testing, SLEDAI 2000 questionnaire, SLICC index, BILAG 2004” at week -4 , week 0, week 2 and every 4 weeks until week 68
4. Proportion of patients with any disease flare (defined as 1 BILAG A or 2 BILAG B flares) is measured by BILAG 2004 at week -4, week 0, week 2 and every 4 weeks until week 68
5. Time to disease flare (defined as 1 BILAG A or 2 BILAG B flares) is measured by BILAG 2004 at week -4 , week 0, week 2 and every 4 weeks until week 68
6. Proportion of patients with a BILAG A or 2 BILAG B flares is measured by BILAG 2004 at 24, 52 and 68 weeks
7. SLEDAI 2000 is measured by “SLEDAI 2000 at 52 weeks
8. Systemic lupus erythematosus disease activity is measured using Subject Global Assessment of Disease Activity (SGADA) at 52 weeks
9. C3 is measured by blood sample testing at week -4 , week 0, week 2 and every 4 weeks until week 68
10. Immunoglobulin levels are measured by blood sample testing at week -4 , week 0, week 2 and every 4 weeks until week 68
11. BAFF (measurement of RNA from whole blood) is measured by blood sample testing at week -4 , week 0, week 12, week 28, week 52 and week 68
12. Cumulative steroid dose during treatment from randomisation is measured by reviewing patient notes at week -4 , week 0, week 2 and every 4 weeks until week 68
13. Proportion of patients decreasing their baseline steroid dose by 50% without flaring from randomisation, or if below 10mg/day at baseline reducing steroid dose to 5mg/day or who discontinue glucocorticoids with stable disease is measured by reviewing patient notes at week -4 , week 0, week 2 and every 4 weeks until week 68
14.How systemic lupus erythematosus effects quality of participants life” is measured using Lupus Quality of Life (Lupus QoL), SF-36 and EQ5D questionnaires at week -4 , week 0, week 2 and every 4 weeks until week 68
15. Suicidality risk is measured using the C-SSRS (Columbia suicide severity rating scale) at week -4 , week 0, week 2 and every 4 weeks until week 68
16. Kinetics of B cell repopulation, B and T cell phenotype and function during repopulation using Flow Cytometry at week -4 , week 0, week 12, week 28, week 52 and week 68

Overall trial start date

21/01/2014

Overall trial end date

31/12/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged between 18 and 75 years
2. Patients with 4 or more criteria for SLE according to the American College of Rheumatology (ACR) 1997 criteria or SLICC 2012 criteria or biopsy proven lupus nephritis with one additional supportive test on at least two occasions (positive ANA, anti-dsDNA antibodies or anti-Sm antibodies)
3. History of anti-dsDNA antibodies detectable at least once in the past taken within one year of screening the patient on the study protocol (ELISA test should be used for Anti dsDNA antibody testing)
4. Patients have received the first infusion of this cycle of B cell depletion therapy (Rituximab) 4-6 weeks before randomisation (week 0, see participant timeline). Previous use of Rituximab is allowed
5. No contraindications to the use of Belimumab
6. Ability to provide informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant exclusion criteria

1. Severe “critical” SLE flare defined as BILAG A flare in CNS system or any SLE manifestation requiring more immunosuppression than allowed within the protocol in the physician's opinion
2. Pregnancy and/or Breast Feeding patients
3. At risk of pregnancy and unwilling to use an acceptable form of birth control contraception (see section 6.3.1.4)
4. Prior use of Belimumab, Atacicept or any biologic therapy (except Rituximab, but no other B cell depleting therapies)
5. Participation in any other interventional trial within the last 6 months
6. eGFR <30mls/min at screening
7. Active infections, including but not limited to:
7.1. Current or past infection with hepatitis B or C as defined by:
7.1.1. Hepatitis B surface antigen positive
7.1.2. Hepatitis B surface antibody positive and hepatitis B core antibody positive
7.1.3. Hepatitis C antibody positive
7.2. Historically positive HIV test or test positive at screening for HIV
7.3. Active TB.
8. Infection history:
8.1. Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria)
8.2. Hospitalization for treatment of infection within 60 days of Day 0
8.3. Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0
9. Receipt of a live-attenuated vaccine within 3 months of week 0 (see participant timeline)
10. In the investigator’s opinion, patients that are at high risk for infection (including but not limited to in dwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent severe urinary tract infection)
11. IgG levels below 4.0 g/L, IgA level < 10 mg/dL (IgG and IgA test must be performed no more than 10 days before study drug commenced for the second inclusion/exclusion criteria assessment at week 0)
12. Primary immunodeficiency
13. History of malignant neoplasm within the last 5 years
14. History of cervical dysplasia CIN Grade III cervical high risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) within the past 3 years. The patient will be eligible after the condition has resolved (e.g., follow-up HPV test is negative or cervical abnormality has been effectively treated >1 year ago)
15. Severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, pulmonary, cardiac, or neurological disease or, in the investigator’s opinion, any other concomitant medical condition or significant abnormal laboratory value that places the participant at risk by participating in this study with the exception of diseases or conditions related to active SLE
16. Comorbidities currently requiring systemic corticosteroid therapy
17. Evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator’s judgement, pose a significant risk
18. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies
19. Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0
20. White blood cells (WBC) <1.5 x 109/L, Neutrophils <1 x 109/L measured up to 10 days before week 0 (study drug commenced)

Recruitment start date

01/10/2016

Recruitment end date

01/05/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University College London Hospital
235 Euston Road
London
NW1 2BU
United Kingdom

Trial participating centre

Sandwell Hospital
Lyndon
West Bromwich
B71 4HJ
United Kingdom

Trial participating centre

Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Hammersmith Hospital
Du Cane Road White City
London
W12 0HS
United Kingdom

Trial participating centre

Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

The Royal London Hospital
Whitechapel Road
London
E1 1BB
United Kingdom

Trial participating centre

Whipps Cross University Hospital
Whipps Cross Road
London
E11 1NR
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom
+44 20 7679 6163
ctu.beatlupus@ucl.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Arthritis Research UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

GlaxoSmithKline foundation

Alternative name(s)

GSK

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Funder name

University College London Biomedical Research Centre

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

01/12/2016: Verified study information with principle investigator.