A Continuation Trial for Subjects With Lupus That Completed Protocol HGS1006-C1056 or HGS1006-C1057

Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Multi-Center, Continuation Trial of Belimumab (HGS1006, LymphoStat-B™)a Fully Human Monoclonal Anti-BLyS Antibody in Subjects With Systemic Lupus Erythematosus (SLE) Who Completed the Phase 3 Protocol HGS1006-C1056 or HGS1006-C1057

ClinicalTrials.gov ID

NCT00712933

Acronym / sponsor ID

112234

Conditions

Systemic Lupus Erythematosus

Keywords

SLE, Belimumab, Antibodies, Systemic Lupus Erythematosus, Lupus, Autoimmune Diseases

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

738 participants (actual)

Lead sponsor

Human Genome Sciences Inc., a GSK CompanyIndustry (pharma, biotech, devices)

Collaborators

GlaxoSmithKline

Study start

30 May 2008 (actual)

Primary completion

9 Dec 2016 (actual)

Study completion

9 Dec 2016 (actual)

First posted

10 Jul 2008 (estimated)

Results

Posted 16 Jan 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

2

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Adverse Events (AE)

   Time frame: Up to 9 years

   An adverse event is defined as any unfavorable or unintended sign, symptom, or disease that is temporally associated with the use of a study agent but is not necessarily caused by the study agent. This includes worsening (example: increase in frequency or severity) of preexisting conditions. Participants with incidences of any event at any time post-baseline are presented by yearly interval. Only treatment-emergent AEs are summarized.

2. AE Rates by System Organ Class (SOC) During the Study

   Time frame: Up to 9 years

   AE rates by SOC adjusting for participant-years on study drug anytime post Baseline are summarized, which included the follow up visits. Only treatment-emergent AEs are summarized. The event rate of an AE was calculated as the number of events per 100 participant years. Participant years were calculated as sum across all participants ([last visit of interval day - first visit of interval day + 1] divided by365). Participant years excluded between study gaps if participant had not started extension study on date of last visit of parent study.

3. Number of Participants With Serious Adverse Events (SAE)

   Time frame: Up to 9 years

   An adverse event resulting in death, is life threatening (ie, an immediate threat to life), inpatient hospitalization, prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or any other situation which is medically important is categorized as SAE. Only treatment-emergent AEs are summarized.

4. SAE Rates by SOC During the Study

   Time frame: Up to 9 years

   SAE rates by SOC adjusting for participants-years on study drug anytime post Baseline are summarized, which included the follow up visits. Only treatment-emergent SAEs are summarized. The event rate of an SAE was calculated as the number of events per 100 participant years. Participants years were calculated as = sum across all participants ([last visit of interval day - first visit of interval day + 1] divided by 365). Participants years excluded between study gaps if participant had not started extension study on date of last visit of parent study.

5. Change From Baseline in Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT) at the Indicated Time Points

   Time frame: Baseline and up to 9 years

   Hematology parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 hematology parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in APTT and PT is summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point

6. Change From Baseline in Platelets (Plt), Lymphocytes (Lymp), Leukocytes (Leu), Eosinophils (Eos), Basophils (Baso), Monocytes (Mono), Neutrophils (Neu), Neutrophils Band Form (NeuBF), Neutrophils Segmented (NeuS) at the Indicated Time Points

   Time frame: Baseline and up to 9 years

   Hematology parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 hematology parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Plt, Lymp, Leu, Eos, Baso, Mono, Neu, NeuBF, and NueS are summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

7. Change From Baseline in Hemoglobin (Hg) at the Indicated Time Points

   Time frame: Baseline and up to 9 years

   Hematology parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 hematology parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Hg is summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

8. Change From Baseline in Hematocrit at the Indicated Time Points

   Time frame: Baseline and up to 9 years

   Hematology parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 hematology parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks). Change from Baseline in Hematocrit is summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

9. Change From Baseline in Erythrocytes (Eryth) at the Indicated Time Points

   Time frame: Baseline and up to 9 years

   Hematology parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 hematology parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Erythrocytes is summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

10. Change From Baseline in Calcium (Ca), Carbon Dioxide (CO2), Chloride, Magnesium (Mg), Phosphate (Phos), Potassium (K), Sodium (Na) at the Indicated Time Points

    Time frame: Baseline and up to 9 years

    Electrolytes parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 electrolytes parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Ca,CO2, Chloride, Mg, Phos, K and Na were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

11. Change From Baseline in Blood Urea Nitrogen/Creatinine (BUN/Cr) at the Indicated Time Points

    Time frame: Baseline and up to 9 years

    Other chemistries parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 other chemistries parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in BUN/Cr is summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

12. Change From Baseline in Albumin (Alb) and Protein (Pro) at the Indicated Time Points

    Time frame: Baseline and up to 9 years

    Other chemistries parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 other chemistries parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Alb and Protein were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

13. Change From Baseline in BUN and Glucose at the Indicated Time Points

    Time frame: Baseline and up to 9 years

    Other chemistries parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 other chemistries were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in BUN and Glucose were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

14. Change From Baseline in Creatinine (Cr) and Urate at the Indicated Time Points

    Time frame: Baseline and up to 9 years

    Other chemistries parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 other chemistries were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Cr and Urate were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

15. Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Levels

    Time frame: Baseline and up to 9 years

    Liver function parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 liver function parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in ALT, ALP, AST, GGT and LDH were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.NA indicates standard deviation was not calculable for a single data point.

16. Change From Baseline in Bilirubin (Bili) Levels

    Time frame: Baseline and up to 9 years

    Liver function parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 liver function parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Bili were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

17. Change From Baseline in Immunoglobulin G (IgG) Levels

    Time frame: Baseline and up to 9 years

    Immunoglobulin (Ig) parameters were assessed at Baseline, Week 4,12,24,36, and 48 during Year 1. From Year 2-9 Ig parameters were assessed at Week 24 and 48 ; Exit visit and at follow-up (up to 8 weeks post infusion). Change from Baseline in Ig G were summarized. The Baseline is defined as For Year 1, Day 0 values for MITT participants who were treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants who were treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. NA indicates standard deviation was not calculable for a single data point.

18. Number of Participants With Immunogenic Response by Year

    Time frame: Up to 9 years

    Immunogenic response was analyzed using serum samples for anti-belimumab antibody measurements in MITT population. Categories of response are Negative, Transient Positive (+) means single + response that does not occur at the final assessment, and Persistent + means + response that occurs at least 2 consecutive assessments or a single result at the final assessment. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

19. Number of Participants With IgG Values Below the Lower Limit of Normal by Year

    Time frame: Up to 9 years

    Blood samples were collected to evaluate IgG levels at Baseline and at Weeks 12, 24 and 48 during Year 1. From Year 2-9, IgG was evaluated at Week 24 and 48 ; Exit visit and at follow-up visit (up to 8 weeks post last infusion). Number of participants with IgG immunoglobulin values below the LLN at each one year interval are presented. Baseline includes Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with Belimumab in the parent study. If a participant had more than one response within a year, then the last response within the year interval (usually the Week 48 assessment) was summarized. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

20. Number of Participants With Shifts From Baseline in Prednisone and Other Steroids Dose by Visit

    Time frame: Up to 9 years

    Participants who had improving SLE disease activity for at least 8 weeks, at the investigator's discretion, the steroid dose was reduced by reduction to 7.5 mg/day. If the participant continued to have stable or improving disease activity after 4 weeks on a reduced dose, then the investigator considered reducing the dose again. Baseline includes extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with Belimumab in the parent study. Number of participants with shifts from Baseline total daily dose category by visit is summarized.

21. Number of Participants With Any SLICC/ ACR Damage Index Worsening (Change > 0) From Baseline by Visit

    Time frame: Up to 9 years

    The SLICC/ACR Damage Index was assessed every 48 weeks and at the exit visit as a measure of disease activity. It was developed to assess the accumulated damage since the onset of the disease. The number of participants with worsening in their SLICC/ACR Damage Index score compared with Baseline have been presented. Worsening was defined as a change in score (post-Baseline visit score - Baseline score) > 0. Baseline includes extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with Belimumab in the parent study. For years in which a participant was withdrawn from the study, the exit visit assessment was used in place of the Week 48 assessment for the year. This value was not carried forward through later years. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2019.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Background: PubMed 26936891Bruce IN, Urowitz M, van Vollenhoven R, Aranow C, Fettiplace J, Oldham M, Wilson B, Molta C, Roth D, Gordon D. Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care. Lupus. 2016 Jun;25(7):699-709. doi: 10.1177/0961203315625119. Epub 2016 Mar 1.
• Background: PubMed 31302695van Vollenhoven RF, Navarra SV, Levy RA, Thomas M, Heath A, Lustine T, Adamkovic A, Fettiplace J, Wang ML, Ji B, Roth D. Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension. Rheumatology (Oxford). 2020 Feb 1;59(2):281-291. doi: 10.1093/rheumatology/kez279.
• Derived from this study: PubMed 33051264Urowitz MB, Ohsfeldt RL, Wielage RC, Dever JJ, Zakerifar M, Asukai Y, Ramachandran S, Joshi AV. Comparative analysis of long-term organ damage in patients with systemic lupus erythematosus using belimumab versus standard therapy: a post hoc longitudinal study. Lupus Sci Med. 2020 Oct;7(1):e000412. doi: 10.1136/lupus-2020-000412.
• Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

110 sites in 28 countries: see every site and its status.