Clinical trial NCT02769195: Utility of a Measure of Lupus Low Disease Activity State (LLDAS) in SLE
Official title: Utility of a Measure of Lupus Low Disease Activity State (LLDAS) in SLE: Pooled Analysis of the HGS1006-C1056 (BLISS-76) and HGS1006-C1057 (BLISS-52) Trials
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Monash University
Sponsor class: OTHER
First posted: 2016-05-11
Enrollment: 1684
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants of the BLISS-76 and BLISS-52 Phase 3 clinical trials. Refer to ClinicalTrials.gov records NCT00410384 and NCT00424476 for further information about these studies.

Brief summary: This study is a secondary, pooled analysis of two completed phase 3 clinical trials:

(i) GSK-HGS1006-C1056 (BLISS-76): A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 76-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects with Systemic Lupus Erythematosus (SLE); and,

(ii) GSK-HGS1006-C1057 (BLISS-52): A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Wk Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)

The study will assess the discriminant validity of a proposed measure of low disease activity (the Lupus Low Disease Activity State, LLDAS) in patients with SLE.

Detailed description: Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease with an estimated incidence of 5-50 cases per 100,000 people. Despite advances in therapy, there is still significant mortality and morbidity associated with this disease. There have been no clearly defined treatment goals in SLE, hindering the development of treat to target approaches and evaluation of new therapies. Although remission is aimed for, it rarely occurs. A more achievable clinical state and treatment goal of low disease activity has been described recently and a preliminary single centre validation study has demonstrated its association with improved outcomes. This endpoint is termed Lupus Low Disease Activity State (LLDAS).

The proposed study will assess the discriminant validity of the proposed LLDAS criteria in a clinical trial dataset. The objective of the research is to validate the Lupus Low Disease Activity State (LLDAS) tool as a study endpoint in SLE. The data available from the belimumab BLISS trials will be used to evaluate the LLDAS score.

The outcome of these studies will be validation of the LLDAS instrument in a clinical trial dataset, for the first time. This will allow future studies to consider incorporating LLDAS attainment as a trial endpoint, for example allowing comparison of frequency of achieving LLDAS to discriminate between treatments.

The findings will be interpreted using statistical methods and will be published / presented to the public and to peers via peer-reviewed publications, conference presentations, and where relevant the lay media.

Eligibility criteria: Key Inclusion Criteria:

* Clinical diagnosis of SLE by ACR criteria.
* Active SLE disease.
* Autoantibody-positive.
* On stable SLE treatment regimen.

Key Exclusion Criteria:

* Pregnant or nursing
* Have received treatment with any B cell targeted therapy.
* Have received treatment with a biological investigational agent in the past year.
* Have received IV cyclophosphamide within 180 days of Day 0.
* Have severe lupus kidney disease.
* Have active central nervous system (CNS) lupus.
* Have required management of acute or chronic infections within the past 60 days.
* Have current drug or alcohol abuse or dependence.
* Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.

Primary outcomes:
measure: Number of participants who attain the Lupus Low Disease Activity State (LLDAS)
timeFrame: 52 weeks
Secondary outcomes:
measure: Number of patients achieving a SLE Responder Index (SRI) Response
timeFrame: 52 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, Wahono CS, Chen SL, Jin O, Morton S, Hoi A, Huq M, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615-21. doi: 10.1136/annrheumdis-2015-207726. Epub 2015 Oct 12.
citation: Oon S, Huq M, Golder V, Ong PX, Morand EF, Nikpour M. Lupus Low Disease Activity State (LLDAS) discriminates responders in the BLISS-52 and BLISS-76 phase III trials of belimumab in systemic lupus erythematosus. Ann Rheum Dis. 2019 May;78(5):629-633. doi: 10.1136/annrheumdis-2018-214427. Epub 2019 Jan 24.