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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02843659




Registration number
NCT02843659
Ethics application status
Date submitted
8/07/2016
Date registered
26/07/2016
Date last updated
4/10/2018

Titles & IDs
Public title
Proof of Concept Study to Evaluate the Efficacy and Safety of BMS-931699 (Lulizumab) or BMS-986142 in Primary Sjögren's Syndrome
Scientific title
A Phase II, Randomized, Multi-Center, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of BMS-931699 (Lulizumab) or BMS-986142 in Subjects With Moderate to Severe Primary Sjögren's Syndrome
Secondary ID [1] 0 0
2016-000101-37
Secondary ID [2] 0 0
IM128-035
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sjögren's Syndrome 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BMS-931699
Treatment: Drugs - BMS-986142
Treatment: Drugs - Placebo

Experimental: BMS-931699 - Subcutaneous weekly injection + daily oral placebo tablets

Experimental: BMS-986142 - Daily oral tablets + subcutaneous placebo (weekly) injection

Placebo Comparator: Placebo - Weekly subcutaneous placebo injection +daily oral placebo tablets


Treatment: Drugs: BMS-931699
Specified dose on specified days

Treatment: Drugs: BMS-986142
Specified dose on specified days

Treatment: Drugs: Placebo
Specified dose on specified days

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in ESSDAI - The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of twelve organ-specific domains in 3 or 4 levels according to their severity. For example, for no disease activity the domain score equals 0 and for high disease activity the domain score equals 3 or 4. Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. The sum of the weighted domain scores is the overall score, which can range from 0 to 123. A higher score indicates more disease activity. Change from baseline was computed as the value at Week 24 minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening
Timepoint [1] 0 0
At baseline and week 12
Secondary outcome [1] 0 0
Mean Change From Baseline in ESSDAI Scores at Week 4 and Week 8 - The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of twelve organ-specific domains in 3 or 4 levels according to their severity. For example, for no disease activity the domain score equals 0 and for high disease activity the domain score equals 3 or 4. Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. The sum of the weighted domain scores is the overall score, which can range from 0 to 123. A higher score indicates more disease activity. Change from baseline was computed as the value at Week 24 minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening
Timepoint [1] 0 0
At baseline, week 4 and week 8
Secondary outcome [2] 0 0
Mean Change From Baseline in ESSPRI Score at Week 4, Week 8, and Week 12. - ESSPRI, also known as EULAR Sjogren's Syndrome Patient Reported Index, measures subjective symptoms of dryness, pain and fatigue. It uses 0-10 numerical scales, one for each domain. The weight of the domains is identical, and the final score is the mean score of the 3 domains.
Timepoint [2] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [3] 0 0
Proportion of Subjects With a > = 3 Point Improvement From Baseline in ESSDAI at Week 12 - The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of twelve organ-specific domains in 3 or 4 levels according to their severity. For example, for no disease activity the domain score equals 0 and for high disease activity the domain score equals 3 or 4. Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. The sum of the weighted domain scores is the overall score, which can range from 0 to 123. A higher score indicates more disease activity. Change from baseline was computed as the value at Week 24 minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening
Timepoint [3] 0 0
At week 12
Secondary outcome [4] 0 0
Proportion of Subjects With Both >= 3 Points Improvement in ESSDAI and >= 1 Point Improvement in ESSPRI From Baseline at Week 12 - The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of twelve organ-specific domains in 3 or 4 levels according to their severity. For example, for no disease activity the domain score equals 0 and for high disease activity the domain score equals 3 or 4. Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. The sum of the weighted domain scores is the overall score, which can range from 0 to 123. A higher score indicates more disease activity. Change from baseline was computed as the value at Week 24 minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening
Timepoint [4] 0 0
At week 12
Secondary outcome [5] 0 0
Proportions of Subjects With >=1 Point of Improvement From Baseline in ESSPRI - ESSPRI, also known as EULAR Sjogren's Syndrome Patient Reported Index, measures subjective symptoms of dryness, pain and fatigue. It uses 0-10 numerical scales, one for each domain. The weight of the domains is identical, and the final score is the mean score of the 3 domains
Timepoint [5] 0 0
At week 12
Secondary outcome [6] 0 0
Mean Change in Baseline in ESSPRI Individual Component of Dryness - ESSPRI, also known as EULAR Sjogren's Syndrome Patient Reported Index, measures subjective symptoms of dryness, pain and fatigue. It uses 0-10 numerical scales, one for each domain. The weight of the domains is identical, and the final score is the mean score of the 3 domains
Timepoint [6] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [7] 0 0
Mean Change in Baseline in ESSPRI Individual Component of Fatigue - ESSPRI, also known as EULAR Sjogren's Syndrome Patient Reported Index, measures subjective symptoms of dryness, pain and fatigue. It uses 0-10 numerical scales, one for each domain. The weight of the domains is identical, and the final score is the mean score of the 3 domains
Timepoint [7] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [8] 0 0
Mean Change in Baseline in ESSPRI Individual Component of Pain - ESSPRI, also known as EULAR Sjogren's Syndrome Patient Reported Index, measures subjective symptoms of dryness, pain and fatigue. It uses 0-10 numerical scales, one for each domain. The weight of the domains is identical, and the final score is the mean score of the 3 domains
Timepoint [8] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [9] 0 0
Mean Change From Baseline in Unstimulated Salivary Flow Rate - Serum and saliva biomarkers (collected from samples obtained during unstimulated and stimulated salivary flow assessments) were measured to determine the potential PD effect of BMS-931699 and BMS-986142 on disease-related protein analytes. These assessments included, but were not limited to, the detection of cytokines and other protein analytes by immunoassays and/or mass spectrometry proteomic profiling.
Timepoint [9] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [10] 0 0
Mean Change From Baseline in Stimulated Salivary Flow Rate - Serum and saliva biomarkers (collected from samples obtained during unstimulated and stimulated salivary flow assessments) were measured to determine the potential PD effect of BMS-931699 and BMS-986142 on disease-related protein analytes. These assessments included, but were not limited to, the detection of cytokines and other protein analytes by immunoassays and/or mass spectrometry proteomic profiling.
Timepoint [10] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [11] 0 0
Mean Change From Baseline in Ocular Surface Staining - The test was performed by instillation of fluorescein dye and either lissamine green or Rose bengal dye to stain the cornea and conjunctiva, respectively. After instilling the dye, the ocular surface was examined through a slit lamp (biomicroscope).
Timepoint [11] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [12] 0 0
Mean Change From Baseline in Schrimer's Test - The test (without anaesthesia) was performed by placing a narrow calibrated filter-paper strip in the inferior cul-de-sac of each eye. Aqueous tear production was measured by the length in millimeters that the strip wets during the 5 minute test period
Timepoint [12] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [13] 0 0
Mean Change From Baseline in the Tear Break-up Time Test - Determined by instilling fluorescein dye and evaluating the stability of the pre-corneal tear film. After several blinks, the tear film is examined using a broad beam of the slit-lamp (biomicroscope) with a cobalt blue filter. The TBUT, defined as the time in seconds between the subjects's last blink and the first appearance of a random dry spot on the corneal surface, is measured 3 times and the mean value is recorded.
Timepoint [13] 0 0
At baseline, week 4, week 8, and week 12
Secondary outcome [14] 0 0
Mean Change From Baseline in Numeric Rating Scale (NRS) for Mouth, Eye and Vaginal Dryness - The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. 0 = No Pain, 1-3 = Mild Pain(nagging, annoying, interfering little with ADLs), 4-6 = Moderate Pain (interferes significantly with ADLs), 7-10 = Severe Pain (disabling; unable to perform ADLs)
Timepoint [14] 0 0
At baseline, at week 2, week 4, week 6, week 8, week 10, week 12, and week 18
Secondary outcome [15] 0 0
Mean Change From Baseline in Subject Global Assessment of Disease Activity (SubGDA) - The subjects overall assessment of disease activity from 0-10 cm VAS scale with 0 being no disease and 10 cm being most severe disease
Timepoint [15] 0 0
At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18
Secondary outcome [16] 0 0
Mean Change Form Baseline in Physician Global Assessment of Disease Activity (phyGDA) - The investigator's or physician's overall assessment of disease activity from 0-10 cm VAS scale with 0 being no disease and 10 cm being most severe disease.
Timepoint [16] 0 0
At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18
Secondary outcome [17] 0 0
Mean Change From Baseline in Short Form-36 (SF-36) - First, precoded numeric values are recoded per the scoring key given in Table 1. Note that all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores. Table 2 lists the items averaged together to create each scale. Items that are left blank(missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered
Timepoint [17] 0 0
At baseline, week 4, week 8, week 12, and week 18
Secondary outcome [18] 0 0
Mean Change From Baseline in Female Sexual Function Index (FSFI) - The Female Sexual Function Index (FSFI), a 19-item questionnaire, has been developed as a brief, multidimensional self-report instrument for assessing the key dimensions of sexual function in women
Timepoint [18] 0 0
At baseline, week 4, week 8, week 12, and week 18
Secondary outcome [19] 0 0
Mean Change From Baseline in Work Participation and Activity Impairment Questionnaire (WPAI) - Affords calculation of 4 scales to measure the impact of IBD on different domains of impairment in work or other activities: absenteeism, presenteeism (impairment at work), productivity loss (overall work impairment), activity impairment
Timepoint [19] 0 0
At baseline, week 4, week 8, week 12, and week 18

Eligibility
Key inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please
visit www.BMSStudyConnect.com



- Subjects diagnosed or classified as having moderate to severe primary Sjögren's
Syndrome based on the 2016 ACR-EULAR Sjögren's Syndrome Classification Criteria for at
least 16 weeks prior to screening

- ESSDAI = 5 including disease activity (any score > 0) in at least one of the following
domains: Glandular, Articular, Hematological, Biological, Lymphadenopathy

- Positive anti-SS-A/Ro and/or anti-SS-B/La autoantibody

- Unstimulated whole saliva secretion > 0.01 ml/min

- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
the start of study drug and must not be pregnant or breastfeeding. Male and female
subjects must be willing to adhere to protocol-mandated highly effective contraception
for the duration of the study and for the protocol-specified follow up period.
Hormone-based contraceptive methods are not permitted
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Secondary Sjögren's syndrome or the presence of any other systemic autoimmune disease
(eg, RA, SLE, multiple sclerosis, vasculitis)

- Very severe primary Sjögren's syndrome or severe complications of primary Sjögren's
syndrome at the time of the screening visit

- Active systemic or latent bacterial (including tuberculosis), viral or fungal
infection, evidence of current or chronic Hepatitis B or C infection, or HIV infection

- Any significant concurrent medical condition at the time of screening or baseline
visit

- Use of methotrexate, cyclophosphamide, cyclosporine, tacrolimus, azathioprine,
mycophenolate mofetil (MMF) or leflunomide within 12 weeks of screening visit

- Previous treatment with biologics therapies either marketed or in development within 6
months prior to screening visit

- Treatment started or an unstable dose of hydroxychloroquine within 8 weeks of
screening visit

- Oral corticosteroids > 10 mg/day within 14 days of dosing (Day 1), corticosteroid
therapy = 1 mg/kg during the 4 weeks preceding enrollment, or intravenous,
intramuscular or intra-articular corticosteroids within 4 weeks of screening visit

Other protocol defined inclusion/exclusion criteria could apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Local Institution - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Mississippi
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New Mexico
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Chile
State/province [15] 0 0
Metropolitana
Country [16] 0 0
Colombia
State/province [16] 0 0
Cundinamarca
Country [17] 0 0
Colombia
State/province [17] 0 0
Bogota
Country [18] 0 0
Colombia
State/province [18] 0 0
Cali
Country [19] 0 0
Italy
State/province [19] 0 0
Pisa
Country [20] 0 0
Mexico
State/province [20] 0 0
Distrito Fededral
Country [21] 0 0
Mexico
State/province [21] 0 0
Jalisco
Country [22] 0 0
Mexico
State/province [22] 0 0
Yucatan
Country [23] 0 0
Mexico
State/province [23] 0 0
Veracruz
Country [24] 0 0
Peru
State/province [24] 0 0
Lima
Country [25] 0 0
Poland
State/province [25] 0 0
Wroclaw
Country [26] 0 0
Puerto Rico
State/province [26] 0 0
San Juan
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Moscow
Country [28] 0 0
South Africa
State/province [28] 0 0
Western CAPE

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the efficacy of treatment with either
lulizumab or BMS-986142 versus placebo in subjects with moderate to severe primary Sjögren's
syndrome as measured by the change from baseline in ESSDAI at Week 12 between active
treatment arms (lulizumab or BMS-986142, respectively) and the placebo arm.
Trial website
https://clinicaltrials.gov/show/NCT02843659
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02843659