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 Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus
• Intervention: Drug: Belimumab
• Enrollment: 142

Participant Flow

Recruitment Details	This was multicenter, open-label continuation study of belimumab plus standard of care (SOC) in Systemic Lupus Erythematosus (SLE) participants who completed study BEL113750 (NCT01345253) in Northeast Asia (Japan and Korea) & participants who completed the open-label extension of C1115 (NCT01484496) in Japan to assess long term safety & efficacy.
Pre-assignment Details	Total 143 participants were screened for this study and 142 participants were enrolled and received study treatment in current study. BEL113750, a 52 week double-blind study; C1115, a 52 week double-blind study followed by a 6 month open-label extension.

Arm/Group Title	Open-label Belimumab 10 mg/kg
Arm/Group Description	Participants received Belimumab 10 milligrams (mg)/kilogram (kg) intravenously (IV) over 1 hour on Week 0, Week 4 and then every 4 weeks until Week 48 of the first year (Study Year 1); on Week 4 and then every 4 weeks until Week 48 of subsequent years during study (up to Study Year 7 Week 4 Visit, which represents a maximum duration of 5 years and 7 months by calendar year in this open-label study. One Study Year is 48 weeks). All participants were continued on their SOC therapies as prescribed by the investigator.
Period Title: Overall Study
Started	142
Completed	104
Not Completed	38
Reason Not Completed
Adverse Event	7
Lack of Efficacy	3
Protocol Violation	1
Lost to Follow-up	1
Investigator Discretion	5
Withdrawal by Subject	20
Death	1

Baseline Characteristics

Arm/Group Title		Open-label Belimumab 10 mg/kg
Arm/Group Description		Participants received Belimumab 10 milligrams (mg)/kilogram (kg) intravenously (IV) over 1 hour on Week 0, Week 4 and then every 4 weeks until Week 48 of the first year (Study Year 1); on Week 4 and then every 4 weeks until Week 48 of subsequent years during study (up to Study Year 7 Week 4 Visit, which represents a maximum duration of 5 years and 7 months by calendar year in this open-label study. One Study Year is 48 weeks). All participants were continued on their SOC therapies as prescribed by the investigator. First belimumab exposure is the first dose in parent study, for participant randomized to belimumab in the parent study; and first OL belimumab dose received (i.e. in either C1115 open-label extension, or BEL114333), for participant randomized to placebo in parent study.
Overall Number of Baseline Participants		142
Baseline Analysis Population Description		Baseline is the last available value prior to the first belimumab exposure.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	142 participants
		34.6 (9.28)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	142 participants
	Female	129 90.8%
	Male	13 9.2%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	142 participants
American Indian or Alaskan Native		1 0.7%
Japanese Heritage		71 50.0%
East Asian Heritage		68 47.9%
Southeast Asian Heritage		2 1.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description	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).
Time Frame	Up to 6 calendar years and 9 months

Outcome Measure Data

Analysis Population Description

Safety Population. All participants in the Enrolled population who received at least one IV dose of belimumab during current study.

Arm/Group Title	Open-label Belimumab 10 mg/kg
Arm/Group Description:	Participants received Belimumab 10 milligrams (mg)/kilogram (kg) intravenously (IV) over 1 hour on Week 0, Week 4 and then every 4 weeks until Week 48 of the first year (Study Year 1); on Week 4 and then every 4 weeks until Week 48 of subsequent years during study (up to Study Year 7 Week 4 Visit, which represents a maximum duration of 5 years and 7 months by calendar year in this open-label study. One Study Year is 48 weeks). All participants were continued on their SOC therapies as prescribed by the investigator. First belimumab exposure is the first dose in parent study, for participant randomized to belimumab in the parent study; and first OL belimumab dose received (i.e. in either C1115 open-label extension, or BEL114333), for participant randomized to placebo in parent study.
Overall Number of Participants Analyzed	142
Measure Type: Count of Participants; Unit of Measure: Participants
Any SAEs	48 33.8%
Any AEs	139 97.9%

2. Secondary Outcome

Title	Percentage of SLE Responder Index (SRI) Responders by Study Visit
Description	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).
Time Frame	Study Years 1 to 7: At Week 24 and 48 Visits, Year 8: only Week 24 Visit

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category title)

Arm/Group Title		Open-label Belimumab 10 mg/kg
Arm/Group Description:		Participants received Belimumab 10 milligrams (mg)/kilogram (kg) intravenously (IV) over 1 hour on Week 0, Week 4 and then every 4 weeks until Week 48 of the first year (Study Year 1); on Week 4 and then every 4 weeks until Week 48 of subsequent years during study (up to Study Year 7 Week 4 Visit, which represents a maximum duration of 5 years and 7 months by calendar year in this open-label study. One Study Year is 48 weeks). All participants were continued on their SOC therapies as prescribed by the investigator. First belimumab exposure is the first dose in parent study, for participant randomized to belimumab in the parent study; and first OL belimumab dose received (i.e. in either C1115 open-label extension, or BEL114333), for participant randomized to placebo in parent study.
Overall Number of Participants Analyzed		142
Measure Type: Number; Unit of Measure: Percentage of Participants
Year 1 Week 24, n=136	Number Analyzed	136 participants
		47.8
Year 1, Week 48, n=133	Number Analyzed	133 participants
		51.1
Year 2, Week 24, n=129	Number Analyzed	129 participants
		55.0
Year 2, Week 48, n=121	Number Analyzed	121 participants
		53.7
Year 3, Week 24, n=103	Number Analyzed	103 participants
		57.3
Year 3, Week 48, n=88	Number Analyzed	88 participants
		68.2
Year 4, Week 24, n=80	Number Analyzed	80 participants
		67.5
Year 4, Week 48, n=60	Number Analyzed	60 participants
		76.7
Year 5, Week 24, n=32	Number Analyzed	32 participants
		71.9
Year 5, Week 48, n=29	Number Analyzed	29 participants
		69.0
Year 6, Week 24, n=24	Number Analyzed	24 participants
		66.7
Year 6, Week 48, n=22	Number Analyzed	22 participants
		68.2
Year 7, Week 24, n=18	Number Analyzed	18 participants
		83.3
Year 7, Week 48, n=13	Number Analyzed	13 participants
		84.6
Year 8, Week 24, n=1	Number Analyzed	1 participants
		100

Adverse Events

Time Frame	Treatment-emergent SAEs and non-serious AEs were collected up to maximum duration of 6 calendar years and 9 months.
Adverse Event Reporting Description	Treatment-emergent SAEs and non-serious AEs were reported for the Safety Population consisted of all participants in the enrolled population who received at least one IV dose of belimumab during current study. Timeframe includes exposure in parent study/up to 16 weeks post infusion of treatment in current study 114333.
Arm/Group Title	Open-label Belimumab 10 mg/kg
Arm/Group Description	Participants received Belimumab 10 milligrams (mg)/kilogram (kg) intravenously (IV) over 1 hour on Week 0, Week 4 and then every 4 weeks until Week 48 of the first year (Study Year 1); on Week 4 and then every 4 weeks until Week 48 of subsequent years during study (up to Study Year 7 Week 4 Visit, which represents a maximum duration of 5 years and 7 months by calendar year in this open-label study. One Study Year is 48 weeks). All participants were continued on their SOC therapies as prescribed by the investigator. First belimumab exposure is the first dose in parent study, for participant randomized to belimumab in the parent study; and first OL belimumab dose received (i.e. in either C1115 open-label extension, or BEL114333), for participant randomized to placebo in parent study.
All-Cause Mortality
	Open-label Belimumab 10 mg/kg
	Affected / at Risk (%)
Total	1/142 (0.70%)
Serious Adverse Events
	Open-label Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events
Total	48/142 (33.80%)
Blood and lymphatic system disorders
Leukopenia † 1	1/142 (0.70%)	1
Lymphadenopathy † 1	1/142 (0.70%)	1
Cardiac disorders
Pericarditis lupus † 1	1/142 (0.70%)	1
Ear and labyrinth disorders
Vertigo † 1	1/142 (0.70%)	1
Endocrine disorders
Diabetes insipidus † 1	1/142 (0.70%)	1
Eye disorders
Cataract † 1	1/142 (0.70%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/142 (0.70%)	1
Haemorrhoidal haemorrhage † 1	1/142 (0.70%)	1
Intestinal perforation † 1	1/142 (0.70%)	1
Large intestine polyp † 1	1/142 (0.70%)	2
Lupus pancreatitis † 1	1/142 (0.70%)	1
General disorders
Pyrexia † 1	2/142 (1.41%)	2
Oedema peripheral † 1	1/142 (0.70%)	3
Infections and infestations
Cellulitis † 1	3/142 (2.11%)	3
Herpes zoster † 1	3/142 (2.11%)	3
Endocarditis † 1	2/142 (1.41%)	2
Pyelonephritis acute † 1	2/142 (1.41%)	2
Abscess jaw † 1	1/142 (0.70%)	1
Atypical pneumonia † 1	1/142 (0.70%)	1
Bacterial pyelonephritis † 1	1/142 (0.70%)	1
Escherichia urinary tract infection † 1	1/142 (0.70%)	1
External ear cellulitis † 1	1/142 (0.70%)	1
Gastroenteritis † 1	1/142 (0.70%)	1
Gastroenteritis salmonella † 1	1/142 (0.70%)	1
Genital herpes zoster † 1	1/142 (0.70%)	1
Herpes dermatitis † 1	1/142 (0.70%)	1
Herpes simplex pharyngitis † 1	1/142 (0.70%)	1
Infectious colitis † 1	1/142 (0.70%)	1
Oral herpes † 1	1/142 (0.70%)	1
Pelvic inflammatory disease † 1	1/142 (0.70%)	1
Pneumonia † 1	1/142 (0.70%)	2
Pneumonia bacterial † 1	1/142 (0.70%)	1
Skin infection † 1	1/142 (0.70%)	1
Tonsillitis † 1	1/142 (0.70%)	1
Tuberculous pleurisy † 1	1/142 (0.70%)	1
Viral upper respiratory tract infection † 1	1/142 (0.70%)	1
Injury, poisoning and procedural complications
Contusion † 1	3/142 (2.11%)	3
Ligament rupture † 1	1/142 (0.70%)	1
Post procedural complication † 1	1/142 (0.70%)	1
Radius fracture † 1	1/142 (0.70%)	1
Road traffic accident † 1	1/142 (0.70%)	1
Tibia fracture † 1	1/142 (0.70%)	1
Investigations
Alanine aminotransferase increased † 1	1/142 (0.70%)	1
Aspartate aminotransferase increased † 1	1/142 (0.70%)	1
Protein urine present † 1	1/142 (0.70%)	1
Metabolism and nutrition disorders
Hypoalbuminaemia † 1	1/142 (0.70%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis † 1	2/142 (1.41%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid adenoma † 1	1/142 (0.70%)	1
Uterine leiomyoma † 1	2/142 (1.41%)	2
Nervous system disorders
Brain stem infarction † 1	1/142 (0.70%)	1
Putamen haemorrhage † 1	1/142 (0.70%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	1/142 (0.70%)	1
Psychiatric disorders
Depression † 1	1/142 (0.70%)	1
Renal and urinary disorders
Acute kidney injury † 1	1/142 (0.70%)	1
Nephrolithiasis † 1	1/142 (0.70%)	1
Ureterolithiasis † 1	1/142 (0.70%)	2
Reproductive system and breast disorders
Menorrhagia † 1	1/142 (0.70%)	1
Respiratory, thoracic and mediastinal disorders
Asphyxia † 1	1/142 (0.70%)	1
Pleurisy † 1	1/142 (0.70%)	1
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus † 1	1/142 (0.70%)	1
Skin ulcer † 1	1/142 (0.70%)	1
Systemic lupus erythematosus rash † 1	1/142 (0.70%)	1
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Open-label Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events
Total	134/142 (94.37%)
Ear and labyrinth disorders
Vertigo † 1	9/142 (6.34%)
Gastrointestinal disorders
Abdominal pain upper † 1	23/142 (16.20%)
Nausea † 1	23/142 (16.20%)
Diarrhoea † 1	22/142 (15.49%)
Constipation † 1	17/142 (11.97%)
Abdominal pain † 1	16/142 (11.27%)
Vomiting † 1	16/142 (11.27%)
Dental caries † 1	13/142 (9.15%)
Dyspepsia † 1	11/142 (7.75%)
General disorders
Pyrexia † 1	19/142 (13.38%)
Oedema peripheral † 1	11/142 (7.75%)
Infections and infestations
Nasopharyngitis † 1	86/142 (60.56%)
Viral upper respiratory tract infection † 1	25/142 (17.61%)
Herpes zoster † 1	23/142 (16.20%)
Upper respiratory tract infection † 1	22/142 (15.49%)
Influenza † 1	20/142 (14.08%)
Gastroenteritis † 1	18/142 (12.68%)
Pharyngitis † 1	14/142 (9.86%)
Bronchitis † 1	13/142 (9.15%)
Cystitis † 1	12/142 (8.45%)
Oral herpes † 1	11/142 (7.75%)
Urinary tract infection bacterial † 1	11/142 (7.75%)
Hordeolum † 1	9/142 (6.34%)
Conjunctivitis † 1	8/142 (5.63%)
Injury, poisoning and procedural complications
Contusion † 1	16/142 (11.27%)
Ligament sprain † 1	11/142 (7.75%)
Thermal burn † 1	8/142 (5.63%)
Musculoskeletal and connective tissue disorders
Back pain † 1	18/142 (12.68%)
Arthralgia † 1	16/142 (11.27%)
Myalgia † 1	16/142 (11.27%)
Pain in extremity † 1	11/142 (7.75%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma † 1	8/142 (5.63%)
Nervous system disorders
Headache † 1	40/142 (28.17%)
Dizziness † 1	11/142 (7.75%)
Psychiatric disorders
Insomnia † 1	17/142 (11.97%)
Reproductive system and breast disorders
Dysmenorrhoea † 1	8/142 (5.63%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	26/142 (18.31%)
Rhinorrhoea † 1	10/142 (7.04%)
Oropharyngeal pain † 1	9/142 (6.34%)
Rhinitis allergic † 1	9/142 (6.34%)
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	13/142 (9.15%)
Rash † 1	12/142 (8.45%)
Eczema † 1	10/142 (7.04%)
Acne † 1	9/142 (6.34%)
Urticaria † 1	9/142 (6.34%)
Vascular disorders
Hypertension † 1	11/142 (7.75%)
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343
• EMail: GSKClinicalSupportHD@gsk.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tanaka Y, Bae SC, Bass D, Curtis P, Chu M, DeRose K, Ji B, Kurrasch R, Lowe J, Meizlik P, Roth DA. Long-term open-label continuation study of the safety and efficacy of belimumab for up to 7 years in patients with systemic lupus erythematosus from Japan and South Korea. RMD Open. 2021 Jul;7(2):e001629. doi: 10.1136/rmdopen-2021-001629.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01597622
• Other Study ID Numbers: 114333
• First Submitted: May 10, 2012
• First Posted: May 14, 2012
• Results First Submitted: September 13, 2019
• Results First Posted: January 9, 2020
• Last Update Posted: March 27, 2020