Clinical trial NCT02119156: Belimumab Treatment Holiday and Treatment Re-start Study in Lupus Patients
Official title: An Open-label, Non-randomized, 52-Week Study to Evaluate Treatment Holidays and Rebound Phenomenon After Treatment With Belimumab 10 mg/kg in Systemic Lupus Erythematosus Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: treatment holiday
PGA
belimumab
Lymphostat-B
rebound
SELENA SLEDAI
Systemic Lupus Erythematosus
immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-04-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the effect of a 24-week withdrawal followed by a 28-week reintroduction of belimumab 10 mg/kg plus standard of care medications in subjects with stable low systemic lupus erythematosus (SLE) disease activity. Rebound phenomenon will be assessed for subjects who have permanently withdrawn from further belimumab treatment.

Detailed description: This study will assess the effect of a 24-week withdrawal of belimumab followed by a 28-week reintroduction of belimumab 10 mg/kg plus standard of care medications on immunogenicity, markers of biological activity, efficacy, and safety in subjects with stable low systemic lupus erythematosus (SLE) disease activity. Additionally, this study will assess rebound phenomenon in subjects with any disease level of SLE who have permanently withdrawn from further belimumab treatment

Eligibility criteria: Inclusion Criteria:

* Received a minimun of 6 months therapy with with belimumab 10 mg/kg in their current SLE belimumab continuation study.
* Be 18 years of age at the Day 0 visit.
* Non-prenant, non-lactating females willing to comply with specific birth control requirements as set forth in the protocol.
* Able to provide written informed consent to participate.
* Subjects who wish to enroll in the control group and the group taking a 6 month belimumab treatment holiday will need a SELENA SLEDAI score of 3 or less after the minimum of 6 months belimumab therapy, as well as having C3 and C4 complement levels at or above the lower limit of the central laboratory reference range, and are on a stable SLE treatment regimen during the 30 day screening period prior to Day 0.
* Subjects who wish to enroll in the long-term discontinuation group have voluntarily withdrawn from their continuation studies.

Exclusion Criteria:

* Subjects who have developed clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE, or experienced an adverse event (AE) in their belimumab continuation study that could, in the opinion of the principle investigator, put the subject at undue risk.
* Subjects who have developed any other medical diseases, laboratory abnormalities, or conditions that, in the opinion of the principle investigator, makes the subject unsuitable for the study.

Primary outcomes:
measure: Median Time to First SLE Flare Index (SFI)
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Rate of SLE Index Flare Per Subject Year
timeFrame: Up to 52 weeks
measure: Median Time to First Severe SFI Flare
timeFrame: Up to 52 weeks
measure: Number of Participants With Evidence of Rebound
timeFrame: Up to 24 weeks
measure: Number of Participants With Confirmed True Positive Belimumab Anti-drug Antibodies (ADA)
timeFrame: Up to 52 weeks
measure: Percentage Change From Baseline in Immunoglobulin
timeFrame: Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40, 48 and 52 weeks
measure: Percentage Change From Baseline in Autoantibody:Anti-double Stranded Deoxyribonucleic Acid (dsDNA)
timeFrame: Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks
measure: Percentage Change From Baseline in Autoantibody: Antinuclear Antibody (ANA)
timeFrame: Baseline (Day 0 from parent studies); Day 0 and 24 and 52 weeks
measure: Percentage Change From Baseline in Complement Levels
timeFrame: Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks
measure: Percentage Change From Baseline in B Cell Subsets
timeFrame: Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40 and 52 weeks
measure: Percentage Change From 24 Week in B Cell Subsets: Treatment Holiday Group (Re-start Phase)
timeFrame: Week 24, 32, 40 and 52 weeks
measure: SELENA SLEDAI Scores Change From Baseline
timeFrame: Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48 and 52 weeks
measure: Number of Days of Daily Prednisone Dose >=7.5 mg/Day and/or Increased by 25 Percent From Day 0 of This Study
timeFrame: Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52
measure: Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Decreased by 25 Percent From Day 0 of This Study
timeFrame: Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Hefei
country: China
facility: GSK Investigational Site
state: Anhui
city: Suzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon, Kyonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bae SC, Bass DL, Chu M, Curtis P, Dimelow R, Harvey L, Ji B, Kurrasch R, Muzaffar S, Punwaney R, Roth DA, Song YW, Xie W, Zhang F. The effect of 24-week belimumab treatment withdrawal followed by treatment restart in patients with SLE: an open-label, non-randomised 52-week study. Arthritis Res Ther. 2022 Feb 16;24(1):46. doi: 10.1186/s13075-022-02723-y.