BEL114333, a Continuation Study of BEL113750 in Subjects With Systemic Lupus Erythematosus (SLE) in Northeast Asia, and in Japan Subjects Completing the Open-label Extension of HGS1006-C1115

• ClinicalTrials.gov Identifier: NCT01597622
• Recruitment Status: Completed
• First Posted: May 14, 2012
• Results First Posted: January 9, 2020
• Last Update Posted: March 27, 2020
• Sponsor: GlaxoSmithKline
• Collaborator: Human Genome Sciences Inc.
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

This study provides subjects who complete the BEL113750 study and subjects who complete the open-label extension of HGS1006-C1115 (referred to as C1115) Study in Japan the option of continuing treatment with belimumab (10 mg/kg intravenously every 4 weeks) for those randomized to belimumab, or the option to begin treatment with belimumab for those randomized to placebo, as an add-on to their standard of care SLE therapy.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: Belimumab	Phase 3

Detailed Description:

This is a multicentre, continuation study of belimumab plus standard of care (SOC) in SLE subjects who completed the Phase III BEL113750 protocol in Northeast Asia or who completed the open-label extension of the HGS1006-C1115 protocol in Japan. This study provides subjects who complete the BEL113750 study the option of continuing treatment with belimumab (10 mg/kg intravenously every 4 weeks) for those randomized to belimumab, or the option to begin treatment with belimumab for those randomized to placebo, as an add-on to their SOC SLE therapy. Subjects participating in this continuation protocol will continue to be monitored for safety and efficacy, as measured by the SLE responder index. Subjects who complete 48 weeks of treatment on the BEL113750 study and who meet inclusion/exclusion criteria, and provide informed consent, will be given the option to enter the continuation study. All subjects will receive belimumab 10 mg/kg IV infused over 1 hour every 4 weeks. Subjects recruited into this study will continue to receive treatment with belimumab until such time as belimumab becomes commercially available in a subject's country of participation, or the subject elects to participate in another belimumab continuation study for SLE, or until either the subject's physician withdraws the subject from the study, or upon the decision by the sponsor to discontinue further development of belimumab for SLE.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 142 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BEL114333, a Multicenter, Continuation Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) Who Completed the Phase III Study BEL113750 in Northeast Asia or Completed the Open-label Extension of HGS1006-C1115 in Japan
• Actual Study Start Date: June 11, 2012
• Actual Primary Completion Date: September 13, 2018
• Actual Study Completion Date: September 13, 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: Open-label Belimumab; Belimumab 10 mg/kg administered intravenously every 4 weeks. All study subjects will receive standard SLE therapies during the study. Subjects will continue to receive belimumab treatment until such time belimumab becomes commercially available in a subject's country of participation, or the subject elects to participate in another belimumab continuation study for SLE, or until either the subject's physician withdraws the subject from the study, or upon the decision by the sponsor to discontinue further development of belimumab for SLE.

Drug: Belimumab; 10 mg/kg administered intravenously over 1 hour every 4 weeks

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Up to 6 calendar years and 9 months ]
   Any untoward medical occurrence in participant, temporally associated with use of medicinal product, whether or not considered related to medicinal product. Any untoward event resulting in death,life threatening,requires hospitalization or prolongation of existing hospitalization,results in disability/incapacity,congenital anomaly/birth defect,medically important were categorized as SAE. Number of participants who had any AE(includes those having non-serious and/or serious AEs) or any SAE are presented.Treatment-emergent AEs are defined as AEs that started on or after first dose of belimumab treatment and for those participants who were randomized to placebo in parent study,ongoing AEs that started before first open-label belimumab dose(in either C1115 open-label extension or BEL114333),worsened (severity,seriousness,relatedness) at any point during the open-label treatment.Timeframe includes exposure in parent study/upto16 weeks post infusion in current study(114333).

Secondary Outcome Measures :

1. Percentage of SLE Responder Index (SRI) Responders by Study Visit [ Time Frame: Study Years 1 to 7: At Week 24 and 48 Visits, Year 8: only Week 24 Visit ]
   SRI response is composite index, defined as percent of participants with>=4 point reduction from Baseline in safety of estrogen in lupus national assessment systemic lupus erythematosus disease activity index (SELENA-SLEDAI) score and no worsening (increase of <0.30 points from Baseline) in physicians global assessment(PGA) &no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment. A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0(no activity) to 3(severe activity). BILAG has no range. Baseline is last available value prior to first belimumab exposure. Year 8 Week 24 visit is the Exit Visit obtained by slotting the Exit Visit to Week 24. Timeframe includes exposure in parent study/upto 4 weeks post infusion (Exit visit) in current study (114333).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Have completed the BEL113750 Protocol in Northeast Asia through Week 48 OR have completed the open-label extension of C1115 in Japan.
• Be able to receive the first dose of belimumab for BEL114333 four weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750 OR be able to receive the first dose of IV belimumab 1 week (plus a 1 week visit window) after the last dose of open-label SC belimumab in C1115..

Exclusion Criteria:

• Have developed clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases), or experienced an adverse event (AE) in the Phase 3 study that could, in the opinion of the principal investigator, put the subject at undue risk.
• Have developed any other medical diseases (e.g., cardiopulmonary), laboratory abnormalities, or conditions (e.g., poor venous access) that in the opinion of the principal investigator, makes the subject unstable for the study.

Contacts and Locations

Locations

Japan

GSK Investigational Site

Chiba, Japan, 275-8580

GSK Investigational Site

Ehime, Japan, 791-0295

GSK Investigational Site

Fukuoka, Japan, 807-8555

GSK Investigational Site

Fukuoka, Japan, 810-8563

GSK Investigational Site

Hiroshima, Japan, 730-8619

GSK Investigational Site

Hiroshima, Japan, 739-0002

GSK Investigational Site

Hokkaido, Japan, 060-8604

GSK Investigational Site

Hokkaido, Japan, 060-8648

GSK Investigational Site

Hyogo, Japan, 675-8545

GSK Investigational Site

Miyagi, Japan, 980-8574

GSK Investigational Site

Nagasaki, Japan, 857-1195

GSK Investigational Site

Okayama, Japan, 710-8522

GSK Investigational Site

Okinawa, Japan, 901-0243

GSK Investigational Site

Tochigi, Japan, 321-0293

GSK Investigational Site

Tokyo, Japan, 104-8560

GSK Investigational Site

Tokyo, Japan, 113-8431

GSK Investigational Site

Tokyo, Japan, 160-8582

GSK Investigational Site

Tokyo, Japan, 162-8655

Korea, Republic of

GSK Investigational Site

Busan, Korea, Republic of, 602-715

GSK Investigational Site

Busan, Korea, Republic of

GSK Investigational Site

Daegu, Korea, Republic of, 700-721

GSK Investigational Site

Incheon, Korea, Republic of, 400-711

GSK Investigational Site

Seoul, Korea, Republic of, 110-744

GSK Investigational Site

Seoul, Korea, Republic of, 133-792

GSK Investigational Site

Seoul, Korea, Republic of, 137-701

GSK Investigational Site

Seoul, Korea, Republic of, 150-713

GSK Investigational Site

Suwon, Kyonggi-do, Korea, Republic of, 443-721

Sponsors and Collaborators

GlaxoSmithKline

Human Genome Sciences Inc.

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Statistical Analysis Plan  [PDF] May 31, 2019

Study Protocol  [PDF] May 16, 2014

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01597622
• Other Study ID Numbers: 114333
• First Posted: May 14, 2012
• Results First Posted: January 9, 2020
• Last Update Posted: March 27, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: https://clinicalstudydatarequest.com/Posting.aspx?ID=20307

Keywords provided by GlaxoSmithKline:

SELENA; belimumab; Lupus; systemic lupus erythematosus; PGA; BLys; SLE Flare Index; continuation; phase III; BILAG; extension; efficacy; SRI; B cell; SLEDAI; safety; Asia; B lymphocyte

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Belimumab; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs