Phase 2 N=86 Randomized Double-blind Treatment

Safety and Efficacy Study of Subcutaneous Belimumab and Intravenous Rituximab Co-administration in Subjects With Primary Sjogren's Syndrome

Sjogren's Syndrome

Bottom Line

View on ClinicalTrials.gov: NCT02631538 ↗

Enrolled (actual)

Serious AEs

10.5%

Results posted

Jun 2021

Primary outcome: Primary: Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE) — 0; 3; 2; 4 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Belimumab (Drug); Rituximab (Drug); Placebo belimumab (Drug); Placebo rituximab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Jun 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE)	0; 3; 2; 4; 12; 24	—
PRIMARY Number of Participants With Adverse Event of Special Interests (AESIs)	0; 0; 0; 1; 4; 2	—
SECONDARY Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time	-2.00; -4.85; -3.87; -4.22; -2.87; -5.32	—
SECONDARY Stimulated Salivary Flow Rate Over Time	0.470; 0.714; 0.425; 0.618; 0.486; 0.754	—
SECONDARY Oral Dryness Numeric Response Scale (NRS) Over Time	7.6; 7.4; 7.2; 7.3; 6.1; 5.7	—
SECONDARY Absolute Values for B-cells (Cluster of Differentiation 20 [CD20]) Within Salivary Gland Biopsy at Week 24	380.21719; 8.65550; 396.86058; 650.76069	—

Summary

This study is a multi-national, multi-center, double-blind (sponsor open), randomized, placebo-controlled trial in subjects with active primary Sjögren's syndrome designed to understand the safety and tolerability profile of belimumab/ rituximab co-administration and of belimumab monotherapy; and to evaluate whether either co-administration therapy or belimumab monotherapy has a substantive effect on disease activity. This study will consist screening period, double blind treatment period, a general follow-up period and individualized follow-up period. Approximately 70 subjects will be recruited into the study initially. At Day 0, subjects will be randomized 1:2:2:2 to one of the four treatment arms placebo arm, belimumab monotherapy arm, co-administration therapy arm and rituximab monotherapy arm. Once a sufficient number of subjects have completed the Week 24, interim analyses and sample size re-estimation will be conducted. The total number of subjects randomized may increase following sample size re-estimation up to a maximum of 120 recruited into the study. Subjects in all arms will receive investigational product (IP) until Week 52 (completion of the treatment phase). All subjects will enter a 16-week general follow-up period after the Week 52 visit or after discontinuation if a subject discontinues IP and withdraws from the treatment phase visits prior to Week 52. After completing the general follow-up period, subjects with cluster of differentiation (CD)19+ B-cell levels below the lower limit of normal (or less than 90 percent [%] of baseline, if baseline value was below lower limit of normal [LLN]) will enter an individualized safety follow-up phase and return to the clinic for visits every 12 weeks with monthly calls between visits to evaluate subjects for any serious adverse events (SAEs) related to IP or study participation, fatal SAEs, and designated adverse event of special interests (AESIs) (i.e., infections, malignancies, or depression, suicide/self-injury), and to check concomitant medications. The total duration of participation of a subject in this study will be approximately up to a maximum of 2 years (i.e., up to Week 104).

Eligibility Criteria

Inclusion Criteria

Age >=18 years, at the time of signing the informed consent.
Documented Primary Sjögren's Syndrome by American European Consensus Group criteria including: either anti-Sjogren's-syndrome-related antigen A (SS-A) or anti-Sjogren's-syndrome-related antigen B (SS-B) positive.
Baseline unstimulated salivary flow >0.0 mL/min or evidence of glandular reserve function (stimulated baseline salivary flow >0.05 mL/min).
Symptomatic oral dryness (>=5/10 on subject completed numeric response scale).
Systemically active disease, ESSDAI >=5 points.
Male and female subjects; females of child bearing potential are eligible if using effective contraception: Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotropin [hCG] test), not lactating, and at least one of the following conditions applies:
Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy.

Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study; otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

Reproductive potential and agrees to follow one of the options in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication up to Week 68 after Day 0.
Ability to understand and comply with the protocol-required procedures and provision of informed consent.

Exclusion Criteria

Diagnosis of secondary Sjögren's syndrome.
Active life-threatening or organ-threatening complications of Sjogren's-syndrome (SS) disease at the time of screening based on treating physician evaluation including but not restricted to (1) vasculitis with renal, digestive, cardiac, pulmonary or central nervous system (CNS) involvement characterized as severe, (2) active CNS or peripheral nervous system (PNS) involvement requiring high dose steroids, (3) severe renal involvement defined by objective measures, (4) lymphoma.
History of major organ transplant (including hematopoietic stem cell transplant).
History of malignancy within past 5 years (with the exception of adequately treated: [1] cervical carcinoma Stage 1B or less, [2] non-invasive basal cell and squamous cell skin carcinoma).
History of infection requiring long term systemic therapy including: (1) history of positive human immunodeficiency virus (HIV) serology, (2) positive serology for Hepatitis C virus (HCV), (3) positive serology for Hepatitis B (HB), defined as: HB surface antigen positive (HBsAg+) OR HB core antibody positive (HBcAb+).
Previous serious opportunistic or atypical infections or hospitalization for treatment of infection within 364 days of Day 0 or use of parenteral (intravenous [IV] or intramuscular [IM]) antibacterials, antivirals, anti-fungals, or anti-parasitic agents within 364 days of prior to Day 0.
Patients in a severely immunocompromised state.
History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
History of significant medical illness (or planned surgical procedure) which in the opinion of the investigator would interfere with the study procedures and / or assessments - including but not limited to immunoglobulin G4 (IgG4) disease or prior head or neck irrad

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Data sourced from ClinicalTrials.gov (NCT02631538). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.