Belimumab Treatment Holiday and Treatment Re-start Study in Lupus Patients

NCT02119156 | Completed Phase 3 Results

• 1 other identifier: 116027
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 20

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 Rebound phenomenon will be assessed for subjects who have permanently withdrawn from further belimumab treatment.

Conditions

Systemic Lupus Erythematosus

Keywords

treatment holiday; PGA; belimumab; Lymphostat-B; rebound; SELENA SLEDAI; Systemic Lupus Erythematosus; immunogenicity

Outcome Measures

Primary Outcomes (1)

• Median Time to First SLE Flare Index (SFI)

  SFI Flare was defined as a mild/moderate or severe flare according to the modified Safety of Estrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) SLE Flare Index (modified excluded severe flares from the SELENA SLEDAI flare assessment that were triggered only by an increase in SELENA SLEDAI score to \>12).Time to first SFI flare is defined as the number of days from Day 0 visit date to the date the participant has a flare (event date - Day 0 visit date + 1) in the 52 Week/Holiday phase; (event date - treatment re-start date + 1) in the Re-start Holiday phase. Day 0 visit date is defined as Day 0 from present study. Median time to first SFI flare is reported; estimated using the product-limit method.

  Up to 52 weeks

Secondary Outcomes (13)

• Rate of SLE Index Flare Per Subject Year

  Up to 52 weeks

• Median Time to First Severe SFI Flare

  Up to 52 weeks

• Number of Participants With Evidence of Rebound

  Up to 24 weeks

• Number of Participants With Confirmed True Positive Belimumab Anti-drug Antibodies (ADA)

  Up to 52 weeks

• Percentage Change From Baseline in Immunoglobulin

  Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40, 48 and 52 weeks

Study Arms (3)

Treatment Holiday Group

EXPERIMENTAL

Subjects in the Treatment Holiday Group will undergo a 6 month belimumab treatment holiday while remaining on standard of care SLE therapy, then re-start belimumab therapy for 6 months while receiving standard of care SLE therapy.

Drug: Belimumab

Control Group

ACTIVE COMPARATOR

Subjects in the Control Group will continue to receive monthly belimumab therapy, in addition to standard of care SLE therapy for 52 weeks.

Drug: Belimumab

Long-Term Discontinuation Group

NO INTERVENTION

Subjects in the Long-Term Discontinuation Group have elected to discontinue further belimumab therapy and will remain on standard of care SLE therapy as directed by the investigator, and agree to return for monthly visits for 52 weeks.

Interventions

Belimumab DRUG

Monthly intravenous infusions dosed as 10 mg/kg body weight

Control Group; Treatment Holiday Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Los Angeles, California, 90048, United States

Location

GSK Investigational Site

Manhasset, New York, 11030, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Hefei, Anhui, 230001, China

Location

GSK Investigational Site

Suzhou, Jiangsu, 215006, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310009, China

Location

GSK Investigational Site

Beijing, 100032, China

Location

GSK Investigational Site

Beijing, 100044, China

Location

GSK Investigational Site

Chiba, 275-8580, Japan

Location

GSK Investigational Site

Ehime, 791-0295, Japan

Location

GSK Investigational Site

Hokkaido, 060-8604, Japan

Location

GSK Investigational Site

Miyagi, 980-8574, Japan

Location

GSK Investigational Site

Nagasaki, 857-1195, Japan

Location

GSK Investigational Site

Tokyo, 104-8560, Japan

Location

GSK Investigational Site

Tokyo, 162-8655, Japan

Location

GSK Investigational Site

Daegu, 700-721, South Korea

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 133-792, South Korea

Location

GSK Investigational Site

Seoul, South Korea

Location

GSK Investigational Site

Suwon, Kyonggi-do, 443-721, South Korea

Location

Related Publications (1)

• 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.

  PMID: 35172878 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Study limitations include the small sample size and differences in Day 0 characteristics between Long-term Discontinuation and Treatment Control groups, which limits the ability to draw inferences.

Results Point of Contact

• Title: GlaxoSmithKline
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 17, 2014
• First Posted: April 21, 2014
• Study Start: May 13, 2014
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Locations

KR (5); CN (5); US (3); JP (7)