Proof of Concept Study to Evaluate the Efficacy and Safety of BMS-931699 (Lulizumab) or BMS-986142 in Primary Sjögren's Syndrome
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| ClinicalTrials.gov Identifier: NCT02843659 |
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Recruitment Status :
Terminated
(Inability to meet protocol objectives)
First Posted : July 26, 2016
Results First Posted : October 4, 2018
Last Update Posted : October 4, 2018
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Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sjögren's Syndrome | Drug: BMS-931699 Drug: BMS-986142 Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 45 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | October 18, 2016 |
| Actual Primary Completion Date : | July 24, 2017 |
| Actual Study Completion Date : | July 24, 2017 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Sjögren syndrome
MedlinePlus related topics:
Sjogren's Syndrome
| Arm | Intervention/treatment |
|---|---|
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Experimental: BMS-931699
Subcutaneous weekly injection + daily oral placebo tablets
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Drug: BMS-931699
Specified dose on specified days
Other Name: lulizumab Drug: Placebo Specified dose on specified days |
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Experimental: BMS-986142
Daily oral tablets + subcutaneous placebo (weekly) injection
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Drug: BMS-986142
Specified dose on specified days Drug: Placebo Specified dose on specified days |
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Placebo Comparator: Placebo
Weekly subcutaneous placebo injection +daily oral placebo tablets
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Drug: Placebo
Specified dose on specified days |
Primary Outcome Measures :
- Mean Change From Baseline in ESSDAI [ Time Frame: At baseline and 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
Secondary Outcome Measures :
- Mean Change From Baseline in ESSDAI Scores at Week 4 and Week 8 [ Time Frame: At baseline, 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
- Mean Change From Baseline in ESSPRI Score at Week 4, Week 8, and Week 12. [ Time Frame: At baseline, 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.
- Proportion of Subjects With a > = 3 Point Improvement From Baseline in ESSDAI at Week 12 [ Time Frame: 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
- Proportion of Subjects With Both >= 3 Points Improvement in ESSDAI and >= 1 Point Improvement in ESSPRI From Baseline at Week 12 [ Time Frame: 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
- Proportions of Subjects With >=1 Point of Improvement From Baseline in ESSPRI [ Time Frame: At 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
- Mean Change in Baseline in ESSPRI Individual Component of Dryness [ Time Frame: At baseline, 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
- Mean Change in Baseline in ESSPRI Individual Component of Fatigue [ Time Frame: At baseline, 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
- Mean Change in Baseline in ESSPRI Individual Component of Pain [ Time Frame: At baseline, 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
- Mean Change From Baseline in Unstimulated Salivary Flow Rate [ Time Frame: At baseline, week 4, week 8, and week 12 ]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.
- Mean Change From Baseline in Stimulated Salivary Flow Rate [ Time Frame: At baseline, week 4, week 8, and week 12 ]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.
- Mean Change From Baseline in Ocular Surface Staining [ Time Frame: At baseline, week 4, week 8, and week 12 ]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).
- Mean Change From Baseline in Schrimer's Test [ Time Frame: At baseline, week 4, week 8, and week 12 ]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
- Mean Change From Baseline in the Tear Break-up Time Test [ Time Frame: At baseline, week 4, week 8, and week 12 ]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.
- Mean Change From Baseline in Numeric Rating Scale (NRS) for Mouth, Eye and Vaginal Dryness [ Time Frame: At baseline, at week 2, week 4, week 6, week 8, week 10, week 12, and week 18 ]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)
- Mean Change From Baseline in Subject Global Assessment of Disease Activity (SubGDA) [ Time Frame: At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18 ]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
- Mean Change Form Baseline in Physician Global Assessment of Disease Activity (phyGDA) [ Time Frame: At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18 ]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.
- Mean Change From Baseline in Short Form-36 (SF-36) [ Time Frame: At baseline, week 4, week 8, week 12, and week 18 ]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
- Mean Change From Baseline in Female Sexual Function Index (FSFI) [ Time Frame: At baseline, week 4, week 8, week 12, and week 18 ]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
- Mean Change From Baseline in Work Participation and Activity Impairment Questionnaire (WPAI) [ Time Frame: At baseline, week 4, week 8, week 12, and week 18 ]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
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
- 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
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843659
Locations
Show 34 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Study Documents (Full-Text)
Documents provided by Bristol-Myers Squibb:
Documents provided by Bristol-Myers Squibb:
Study Protocol [PDF] February 13, 2017
Statistical Analysis Plan [PDF] May 15, 2017
Additional Information:
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02843659 |
| Other Study ID Numbers: |
IM128-035 2016-000101-37 ( EudraCT Number ) |
| First Posted: | July 26, 2016 Key Record Dates |
| Results First Posted: | October 4, 2018 |
| Last Update Posted: | October 4, 2018 |
| Last Verified: | October 2018 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Sjogren's Syndrome Syndrome Disease Pathologic Processes Arthritis, Rheumatoid Arthritis Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Xerostomia |
Salivary Gland Diseases Mouth Diseases Stomatognathic Diseases Dry Eye Syndromes Lacrimal Apparatus Diseases Eye Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |