Trial Outcomes & Findings for Proof of Concept Study to Evaluate the Efficacy and Safety of BMS-931699 (Lulizumab) or BMS-986142 in Primary Sjögren's Syndrome (NCT NCT02843659)

NCT ID: NCT02843659

Last Updated: 2018-10-04

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

At baseline and week 12

Results posted on

2018-10-04

Participant Flow

45 subjects enrolled, 18 subjects were randomized/treated. 15 subjects didn't complete the treatment period. The study was terminated and the remaining 15 randomized subjects who had not yet completed the double-blind period entered the follow-up period. Of the 15 subjects who entered the follow-up period, 12 did not complete the follow-up period

Participant milestones

Participant milestones
Measure
BMS-931699/Lulizumab Injection
(12.5mg/vial, 12.5mg/mL) for subcutaneous (SC)
BMS-986142 50 mg Tablet (Round) or 150 mg Tablet (Oval)
For oral administration, 350 mg
Placebo
For BMS-986142 50 mg tablet (round) or 150 mg tablet
Overall Study
STARTED
5
6
7
Overall Study
COMPLETED
1
0
2
Overall Study
NOT COMPLETED
4
6
5

Reasons for withdrawal

Reasons for withdrawal
Measure
BMS-931699/Lulizumab Injection
(12.5mg/vial, 12.5mg/mL) for subcutaneous (SC)
BMS-986142 50 mg Tablet (Round) or 150 mg Tablet (Oval)
For oral administration, 350 mg
Placebo
For BMS-986142 50 mg tablet (round) or 150 mg tablet
Overall Study
Subject Withdrew Consent
0
0
1
Overall Study
Administrative Reason by Sponsor
4
5
4
Overall Study
Adverse Event
0
1
0

Baseline Characteristics

Proof of Concept Study to Evaluate the Efficacy and Safety of BMS-931699 (Lulizumab) or BMS-986142 in Primary Sjögren's Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
BMS-931699/Lulizumab Injection
n=5 Participants
(12.5mg/vial, 12.5mg/mL) for subcutaneous (SC)
BMS-986142 50 mg Tablet (Round) or 150 mg Tablet (Oval)
n=6 Participants
For oral administration, 350 mg
Placebo
n=7 Participants
For BMS-986142 50 mg tablet (round) or 150 mg tablet
Total
n=18 Participants
Total of all reporting groups
Age, Continuous
49.2 Years
STANDARD_DEVIATION 11.34 • n=5 Participants
51.2 Years
STANDARD_DEVIATION 8.77 • n=7 Participants
52.6 Years
STANDARD_DEVIATION 13.30 • n=5 Participants
51.2 Years
STANDARD_DEVIATION 11.41 • n=4 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
6 Participants
n=7 Participants
7 Participants
n=5 Participants
18 Participants
n=4 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race/Ethnicity, Customized
White
4 participants
n=5 Participants
4 participants
n=7 Participants
7 participants
n=5 Participants
15 participants
n=4 Participants
Race/Ethnicity, Customized
Black or African American
0 participants
n=5 Participants
0 participants
n=7 Participants
0 participants
n=5 Participants
0 participants
n=4 Participants
Race/Ethnicity, Customized
Asian
0 participants
n=5 Participants
0 participants
n=7 Participants
0 participants
n=5 Participants
0 participants
n=4 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 participants
n=5 Participants
0 participants
n=7 Participants
0 participants
n=5 Participants
0 participants
n=4 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
0 participants
n=5 Participants
0 participants
n=7 Participants
0 participants
n=5 Participants
0 participants
n=4 Participants
Race/Ethnicity, Customized
Other
1 participants
n=5 Participants
2 participants
n=7 Participants
0 participants
n=5 Participants
3 participants
n=4 Participants

PRIMARY outcome

Timeframe: At baseline and week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4 and week 8

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, and week 12

Population: The study was terminated and data is not reported for privacy reasons

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, at week 2, week 4, week 6, week 8, week 10, week 12, and week 18

Population: The study was terminated and data is not reported for privacy reasons

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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 2, week 4, week 6, week 8, week 10, week 12, and week 18

Population: The study was terminated and data is not reported for privacy reasons

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, week 12, and week 18

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, week 12, and week 18

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, week 4, week 8, week 12, and week 18

Population: The study was terminated and data is not reported for privacy reasons

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

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Lulizumab (BMS-931699) 12.5mg QW

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

BMS-986142 350 mg QD

Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=7 participants at risk
Subjects received subcutaneous (SC) injection of placebo matched to 12.5 milligram (mg) lulizumab (BMS-931699) weekly (QW) and oral tablets of placebo matched to 350 mg BMS-986142 once daily (QD) for 12 weeks.
Lulizumab (BMS-931699) 12.5mg QW
n=5 participants at risk
Subjects received SC injection of 12.5 mg lulizumab (BMS-931699) QW and oral tablets of placebo matched to 350 mg BMS-986142 QD for 12 weeks.
BMS-986142 350 mg QD
n=6 participants at risk
Subjects received oral tablets of 350 mg BMS-986142 QD and placebo matched to SC injection of 12.5 mg lulizumab (BMS-931699) QW for 12 weeks.
Blood and lymphatic system disorders
Thrombocytopenia
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks

Other adverse events

Other adverse events
Measure
Placebo
n=7 participants at risk
Subjects received subcutaneous (SC) injection of placebo matched to 12.5 milligram (mg) lulizumab (BMS-931699) weekly (QW) and oral tablets of placebo matched to 350 mg BMS-986142 once daily (QD) for 12 weeks.
Lulizumab (BMS-931699) 12.5mg QW
n=5 participants at risk
Subjects received SC injection of 12.5 mg lulizumab (BMS-931699) QW and oral tablets of placebo matched to 350 mg BMS-986142 QD for 12 weeks.
BMS-986142 350 mg QD
n=6 participants at risk
Subjects received oral tablets of 350 mg BMS-986142 QD and placebo matched to SC injection of 12.5 mg lulizumab (BMS-931699) QW for 12 weeks.
Infections and infestations
Upper respiratory tract infection
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Infections and infestations
Urinary tract infection
14.3%
1/7 • Number of events 1 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Infections and infestations
Bronchitis
14.3%
1/7 • Number of events 1 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Infections and infestations
Gastroenteritis
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Infections and infestations
Gastroenteritis viral
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Infections and infestations
Influenza
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Infections and infestations
Soft tissue infection
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
General disorders
Fatigue
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
General disorders
Injection site haematoma
14.3%
1/7 • Number of events 1 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
General disorders
Injection site reaction
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
General disorders
Pain
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
General disorders
Sensation of foreign body
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Investigations
Alanine aminotransferase increased
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 2 • Up to 18 weeks
General disorders
Anticoagulation drug level above therapeutic
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Investigations
Aspartate aminotransferase increased
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Investigations
Blood pressure increased
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Gastrointestinal disorders
Gastritis
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Gastrointestinal disorders
Gastrointestinal inflammation
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Metabolism and nutrition disorders
Hypertriglyceridaemia
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Metabolism and nutrition disorders
Hypokalaemia
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Metabolism and nutrition disorders
Vitamin B12 deficiency
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Musculoskeletal and connective tissue disorders
Muscle spasms
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Blood and lymphatic system disorders
Iron deficiency anaemia
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Injury, poisoning and procedural complications
Stress fracture
14.3%
1/7 • Number of events 1 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Nervous system disorders
Headache
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Psychiatric disorders
Depression
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks
Skin and subcutaneous tissue disorders
Urticaria
0.00%
0/7 • Up to 18 weeks
0.00%
0/5 • Up to 18 weeks
16.7%
1/6 • Number of events 1 • Up to 18 weeks
Vascular disorders
Hypertension
0.00%
0/7 • Up to 18 weeks
20.0%
1/5 • Number of events 1 • Up to 18 weeks
0.00%
0/6 • Up to 18 weeks

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Results disclosure agreements

  • Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
  • Publication restrictions are in place

Restriction type: OTHER