Sjogren's SyndromePhase 2NCT02631538
Safety and Efficacy Study of Subcutaneous Belimumab and Intravenous Rituximab Co-administration in Subjects With Primary Sjogren's Syndrome
A Phase 2 study testing Belimumab and Rituximab in people with Sjogren's Syndrome, run by GlaxoSmithKline at 36 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sjogren's Syndrome
- What is being tested?
- Belimumab and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 36 sitesin 10 countries
- Study dates
- 17 Feb 2016to 23 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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 irradiation.
- Severe heart failure (New York Heart Association, Class IV) or other severe, uncontrolled cardiac disease.
- Tuberculosis (TB), defined as: prior history of TB infection; suspicion of TB infection or current TB infection
- At risk of suicide, as indicated by a lifetime history of attempted suicide or significant suicidal ideation over the 6 months prior to the screening visit; or, if in the Investigator's judgment, the subject is at risk for a suicide attempt.
- Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) - not otherwise explained - or confirmed PML.
- Electrocardiogram (ECG) showing a clinically significant abnormality at Screening or showing an average corrected QT using Bazett's formula (QTcB) or corrected QT using Fridericia's formula (QTcF) interval >=450 milliseconds (msec) (>=480 msec for subjects with a Bundle Branch Block) over 3 consecutive ECGs.
- Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Use of systemic immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), mizoribine, calcineurin inhibitors [e.g., tacrolimus, cyclosporine], sirolimus, 6-mercaptopurine, or thalidomide within 60 days prior to Day 0.
- Have received cyclophosphamide within 180 days prior to Day 0.
- Have received anti- B lymphocyte stimulator (BLyS), anti-CD 20, anti-CD22 or anti-CD52 or any other B-cell depleting agent within 364 days prior to Day 0.
- Have received abatacept or any biologic agent within 180 day prior to Day 0 (with exception of denosumab).
- Have received intravenous immunoglobulin (IVIG) or plasmapheresis within 90 days prior to Day 0.
- Have received oral steroid >10 milligram (mg) prednisone equivalent/day within 30 days prior to Day 0 or oral steroid >20 mg prednisone equivalent / day for a minimum of two consecutive weeks within 60 days prior to Day 0. Have received parenteral steroid within 60 days prior to Day 0.
- Have received a live vaccine within 30 days of Day 0.
- Current participation in any other interventional trial.
- Planned blood donation during the treatment and follow up periods of the study.
- Subjects who are unable or unwilling to administer, or to have a caregiver administer subcutaneous injections.
- Drug or alcohol abuse or dependence.
- History of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or human anti-chimeric antibody or history of hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.
- Have an IgA deficiency (IgA level <10 milligram per deciliter [mg/dL]).
- Any of the following screening laboratory values: White blood cells (WBC) <2 x 10^9/L; Neutrophils <1.5 x 10^9/Liter (L); Circulating IgG or IgM levels <lower limit of normal (according to central laboratory range); Aspartate aminotransferase (AST) >2.0 times the upper limit of normal; Alkaline phosphatase (ALP) >1.5 times the upper limit of normal; Bilirubin >1.5 times the upper limit of normal; CD4 count <400 cells per cubic millimetre (cells/mm^3); CD8 count <150 cells/mm^3; CD19+ B-lymphocyte counts <0.1 x 10^9/L.
Trial locations and contacts
36 sites in 10 countries.
36 sites in 10 countries
France9 sites
GSK Investigational Site
Bordeaux, 33000
GSK Investigational Site
Le Kremlin-Bicêtre, 94275
GSK Investigational Site
Lille, 59037
GSK Investigational Site
Paris, 75012
GSK Investigational Site
Paris, 75013
GSK Investigational Site
Paris, 75014
GSK Investigational Site
Paris, 75475
GSK Investigational Site
Paris, 75651
GSK Investigational Site
Strasbourg, 67098
Germany5 sites
GSK Investigational Site
Bad Abbach, 93077
GSK Investigational Site
Berlin, 10117
GSK Investigational Site
Hamburg, 22763
GSK Investigational Site
Mainz, Rhineland-Palatinate, 55131
GSK Investigational Site
Tübingen, Baden-Wurttemberg, 72076
Italy5 sites
GSK Investigational Site
Brescia, 25123
GSK Investigational Site
Padova, 35128
GSK Investigational Site
Perugia, Umbria, 06122
GSK Investigational Site
Pisa, Tuscany, 56126
GSK Investigational Site
Udine, Friuli Venezia Giulia, 33100
Spain4 sites
GSK Investigational Site
Barcelona, 08034
GSK Investigational Site
L'Hospitalet de Llobregat, 08907
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Madrid, 28050
United Kingdom4 sites
GSK Investigational Site
Edgbaston, B15 2GW
GSK Investigational Site
London, E1 4DG
GSK Investigational Site
Newcastle upon Tyne, NE1 4LP
GSK Investigational Site
Swindon, Wiltshire, SN3 6BB
Argentina2 sites
GSK Investigational Site
Buenos Aires, C1111AL
GSK Investigational Site
Córdoba, 5000
Canada2 sites
GSK Investigational Site
Toronto, Ontario, M5T 2S8
GSK Investigational Site
Trois-Rivières, Quebec, G8Z 1Y2
Netherlands2 sites
GSK Investigational Site
Amsterdam, 1081 HZ
GSK Investigational Site
Rotterdam, 3015 CE
Sweden2 sites
GSK Investigational Site
Malmö, SE-205 02
GSK Investigational Site
Stockholm, SE-141 86
About this study
Official title: A Randomized, Double Blind (Sponsor Open), Comparative, Multicenter Study to Evaluate the Safety and Efficacy of Subcutaneous Belimumab (GSK1550188) and Intravenous Rituximab Co-administration in Subjects With Primary Sjögren's Syndrome
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.
Read more
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).
- Conditions
- Sjogren's Syndrome
- Being tested
- Belimumab, Rituximab, Placebo belimumab, Placebo rituximab
- Keywords
- Subcutaneous, Rituximab, Intravenous, Safety, Efficacy, Sjogren's syndrome, Belimumab
- Medical subject headings
- Sjogren's Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelimumabDrug
Belimumab will be provided as a 200 mg sterile, liquid product in a prefilled syringe. Each syringe contains 1.0 mL of 200 mg/mL belimumab. Each syringe will be a single use.
RituximabDrug
Rituximab will be provided as a 100 mg concentrated solution for infusion. It is a clear, colorless liquid.
Placebo belimumabDrug
The placebo control will be provided as a sterile liquid product in a prefilled syringe. Each syringe will be of a single use.
Placebo rituximabDrug
Placebo rituximab will be provided as solution for infusion. It is a clear, colorless liquid.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects will receive belimumab placebo weekly subcutaneous injections to Week 52 and rituximab placebo infusions at Weeks 8 and 10. Receives: Drug: Placebo belimumab; Drug: Placebo rituximab |
| Belimumab monotherapy | Experimental | Subjects will receive 200 mg weekly subcutaneous injections of belimumab to Week 52 and placebo rituximab infusions at Weeks 8 and 10. Receives: Drug: Belimumab; Drug: Placebo rituximab |
| Belimumab and Rituximab co-administration therapy | Experimental | Subjects will receive belimumab 200 mg SC weekly for 24 weeks followed by weekly placebo belimumab injections to Week 52 with rituximab 1000 mg intravenously at Weeks 8 and 10. Receives: Drug: Belimumab; Drug: Rituximab; Drug: Placebo belimumab |
| Rituximab monotherapy | Active comparator | Subjects will receive 1000 mg IV rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of placebo belimumab to Week 52. Receives: Drug: Rituximab; Drug: Placebo belimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations based on medical or scientific judgment and is associated with liver injury and impaired liver function. Data for number of participants with SAE and non-SAE has been summarized.
Measured: Up to Week 68
Number of Participants With Adverse Event of Special Interests (AESIs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AESIs were Malignant Neoplasms, Post-Administration Systemic Reactions (PASR), All Infections of Special Interest (opportunistic infections, herpes zoster, tuberculosis and sepsis), Depression/suicide/self-injury, Deaths and study specific AESI which includes: severe skin reaction per GlaxoSmithKline (GSK) Adjudication, cardiac disorders, Posterior Reversible Encephalopathy Syndrome (PRES) and Progressive multifocal leukoencephalopathy (PML). Data for number of participants with AESI has been summarized.
Measured: Up to Week 68
Secondary outcomes (4)
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time
The ESSDAI is a physician assessed disease activity index developed by EULAR consortium consisting of twelve different clinically relevant organ specific domains; cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and biological. Each domain has 3 or 4 possible activity levels (i.e., no, low, moderate, high [if available]) using a 4-point scale, ranging from 0 (No activity) to 3 (High activity). Higher score indicates high disease activity. Each domain is assigned a weight between 1 and 6. The Total ESSDAI Scores are obtained by multiplying the level of activity (domain score) by the domain weights, ranges between 0 (no activity) and 123 (highest activity). Higher score indicates more disease activity. Baseline value is the screening visit value (within 35 days prior to Day 0). Change from Baseline was defined as the post-dose visit value minus Baseline value.
Measured: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68
Stimulated Salivary Flow Rate Over Time
Participants were instructed to chew a piece of paraffin wax for a period of 5 minutes and saliva was collected. The volume of saliva (milliliter) was divided by the duration of the test (minutes) to calculate the stimulated salivary flow rate (milliliter per minute). Baseline value is the screening visit value (within 35 days prior to Day 0).
Measured: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68
Oral Dryness Numeric Response Scale (NRS) Over Time
Oral dryness was reported by participants on a numeric response scale, ranging from 0 (no dryness) to 10 (maximal dryness), higher score indicates worst imaginable dryness. Baseline value is the screening visit value (within 35 days prior to Day 0).
Measured: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68
Absolute Values for B-cells (Cluster of Differentiation 20 [CD20]) Within Salivary Gland Biopsy at Week 24
Minor salivary gland biopsies were taken for histological analysis to quantify CD20 B Cells.
Measured: At Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2015 (estimated)
- Study start17 Feb 2016
- Primary completion23 Jun 2020
- Study completion23 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sjogren's SyndromeStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02631538
- Sponsor's protocol ID
- 201842
- Other IDs
- 2015-000400-26, 2015
- Status last verified
- May 2021
- First submitted
- 14 Dec 2015
- Last updated
- 9 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Mariette X, Barone F, Baldini C, Bootsma H, Clark KL, De Vita S, Gardner DH, Henderson RB, Herdman M, Lerang K, Mistry P, Punwaney R, Seror R, Stone J, van Daele P, van Maurik A, Wisniacki N, Roth DA, Tak PP. A randomized, phase II study of sequential belimumab and rituximab in primary Sjogren's syndrome. JCI Insight. 2022 Dec 8;7(23):e163030. doi: 10.1172/jci.insight.163030.
PubMed 36477362Raymond K, Maher S, Saucier CD, O'Connor M, Yarlas A, Kosinski M, Chen WH, Gairy K. Validation of the PROFAD-SSI-SF in Patients with Primary Sjogren's Syndrome with Organ Involvement: Results of Qualitative Interviews and Psychometric Analyses. Rheumatol Ther. 2023 Feb;10(1):95-115. doi: 10.1007/s40744-022-00493-2. Epub 2022 Oct 13.
PubMed 36227531
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind (Sponsor Open), Comparative, Multicenter Study to Evaluate the Safety and Efficacy of Subcutaneous Belimumab (GSK1550188) and Intravenous Rituximab Co-administration in Subjects With Primary Sjögren's Syndrome
- ClinicalTrials.gov ID
- NCT02631538
- Acronym / sponsor ID
- 201842
- Conditions
- Sjogren's Syndrome
- Keywords
- Subcutaneous, Rituximab, Intravenous, Safety, Efficacy, Sjogren's syndrome, Belimumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Feb 2016 (actual)
- Primary completion
- 23 Jun 2020 (actual)
- Study completion
- 23 Jun 2020 (actual)
- First posted
- 16 Dec 2015 (estimated)
- Results
- Posted 9 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo belimumab, Drug: Placebo rituximabSubjects will receive belimumab placebo weekly subcutaneous injections to Week 52 and rituximab placebo infusions at Weeks 8 and 10. |
| Belimumab monotherapy | Experimental | Drug: Belimumab, Drug: Placebo rituximabSubjects will receive 200 mg weekly subcutaneous injections of belimumab to Week 52 and placebo rituximab infusions at Weeks 8 and 10. |
| Belimumab and Rituximab co-administration therapy | Experimental | Drug: Belimumab, Drug: Rituximab, Drug: Placebo belimumabSubjects will receive belimumab 200 mg SC weekly for 24 weeks followed by weekly placebo belimumab injections to Week 52 with rituximab 1000 mg intravenously at Weeks 8 and 10. |
| Rituximab monotherapy | Active comparator | Drug: Rituximab, Drug: Placebo belimumabSubjects will receive 1000 mg IV rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of placebo belimumab to Week 52. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (30 listed)
- 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+).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelimumabBelimumab will be provided as a 200 mg sterile, liquid product in a prefilled syringe. Each syringe contains 1.0 mL of 200 mg/mL belimumab. Each syringe will be a single use. | Drug | Belimumab and Rituximab co-administration therapy, Belimumab monotherapy |
| RituximabRituximab will be provided as a 100 mg concentrated solution for infusion. It is a clear, colorless liquid. | Drug | Belimumab and Rituximab co-administration therapy, Rituximab monotherapy |
| Placebo belimumabThe placebo control will be provided as a sterile liquid product in a prefilled syringe. Each syringe will be of a single use. | Drug | Belimumab and Rituximab co-administration therapy, Placebo, Rituximab monotherapy |
| Placebo rituximabPlacebo rituximab will be provided as solution for infusion. It is a clear, colorless liquid. | Drug | Belimumab monotherapy, Placebo |
Primary outcome
Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE)
Time frame: Up to Week 68
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations based on medical or scientific judgment and is associated with liver injury and impaired liver function. Data for number of participants with SAE and non-SAE has been summarized.
Number of Participants With Adverse Event of Special Interests (AESIs)
Time frame: Up to Week 68
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AESIs were Malignant Neoplasms, Post-Administration Systemic Reactions (PASR), All Infections of Special Interest (opportunistic infections, herpes zoster, tuberculosis and sepsis), Depression/suicide/self-injury, Deaths and study specific AESI which includes: severe skin reaction per GlaxoSmithKline (GSK) Adjudication, cardiac disorders, Posterior Reversible Encephalopathy Syndrome (PRES) and Progressive multifocal leukoencephalopathy (PML). Data for number of participants with AESI has been summarized.
4 secondary outcomes
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time
Time frame: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68
Stimulated Salivary Flow Rate Over Time
Time frame: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68
Oral Dryness Numeric Response Scale (NRS) Over Time
Time frame: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68
Absolute Values for B-cells (Cluster of Differentiation 20 [CD20]) Within Salivary Gland Biopsy at Week 24
Time frame: At Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36477362Mariette X, Barone F, Baldini C, Bootsma H, Clark KL, De Vita S, Gardner DH, Henderson RB, Herdman M, Lerang K, Mistry P, Punwaney R, Seror R, Stone J, van Daele P, van Maurik A, Wisniacki N, Roth DA, Tak PP. A randomized, phase II study of sequential belimumab and rituximab in primary Sjogren's syndrome. JCI Insight. 2022 Dec 8;7(23):e163030. doi: 10.1172/jci.insight.163030.
- Derived from this study: PubMed 36227531Raymond K, Maher S, Saucier CD, O'Connor M, Yarlas A, Kosinski M, Chen WH, Gairy K. Validation of the PROFAD-SSI-SF in Patients with Primary Sjogren's Syndrome with Organ Involvement: Results of Qualitative Interviews and Psychometric Analyses. Rheumatol Ther. 2023 Feb;10(1):95-115. doi: 10.1007/s40744-022-00493-2. Epub 2022 Oct 13.
- 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.
GSK Clinical Trials study director
GlaxoSmithKline
36 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belimumab and Rituximab in people with Sjogren's Syndrome, run by GlaxoSmithKline at 36 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in France, Germany, Italy, Spain, United Kingdom and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE) (time frame: Up to Week 68). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02631538, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2021.