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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02631538
• Date of registration: 14/12/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Safety and Efficacy Study of Subcutaneous Belimumab and Intravenous Rituximab Co-administration in Subjects With Primary Sjogren's Syndrome
• Scientific 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
• Date of first enrolment: February 17, 2016
• Target sample size: 86
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02631538
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Argentina, Canada, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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:

1. 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.

2. 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 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Sjogren's Syndrome

Intervention(s)

Drug: Belimumab

Drug: Placebo rituximab

Drug: Placebo belimumab

Drug: Rituximab

Primary Outcome(s)

Number of participants with AESIs [Time Frame: Up to Week 68]

Number of participants with SAEs [Time Frame: Up to Week 68]

Secondary Outcome(s)

Stimulated salivary flow over time [Time Frame: Up to Week 68]

Oral dryness numeric response scale over time [Time Frame: Up to Week 68]

B cell quantification within salivary gland biopsy at Week 24 [Time Frame: Week 24]

The European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) score over time [Time Frame: Up to Week 68]

Secondary ID(s)

2015-000400-26

201842

Source(s) of Monetary Support

Please refer to primary and secondary sponsors