Trial Outcomes & Findings for Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis (NCT NCT02465437)

Last Updated: 2021-04-21

Results Overview

The overall number of subjects with TEAE's per treatment group during active dosing (Days 1-84) plus the 28 day follow-up.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Part A: Day 113

Results posted on

2021-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	Lenabasum (JBT-101) 5 mg QD/20 mg BID Lenabasum 5 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum (JBT-101) 20 mg QD/20 mg BID Lenabasum 20 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum (JBT-101) 20 mg BID/20 mg BID Lenabasum 20 mg BID on Days 1-84.	Placebo Placebo BID on Days 1-84.
Overall Study STARTED	9	9	9	15
Overall Study COMPLETED	8	8	8	14
Overall Study NOT COMPLETED	1	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenabasum (JBT-101) 5 mg QD/20 mg BID Lenabasum 5 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum (JBT-101) 20 mg QD/20 mg BID Lenabasum 20 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum (JBT-101) 20 mg BID/20 mg BID Lenabasum 20 mg BID on Days 1-84.	Placebo Placebo BID on Days 1-84.
Overall Study Physician Decision	0	0	1	0
Overall Study Withdrawal by Subject	1	0	0	1
Overall Study Adverse Event	0	1	0	0

Baseline Characteristics

Note: One subject in the Placebo cohort did not have a FVC % predicted measurement conducted, as such, the total number of subjects in the placebo cohort for FVC % predicted is n = 14 and for the total population, n = 41.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenabasum (JBT-101) 5 mg QD/20 mg BID n=9 Participants Lenabasum 5 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum (JBT-101) 20 mg QD/20 mg BID n=9 Participants Lenabasum 20 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum (JBT-101) 20 mg BID/20 mg BID n=9 Participants Lenabasum 20 mg BID on Days 1-84.	Placebo n=15 Participants Placebo BID on Days 1-84.	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=9 Participants	9 Participants n=9 Participants	7 Participants n=9 Participants	15 Participants n=15 Participants	39 Participants n=42 Participants
Age, Categorical >=65 years	1 Participants n=9 Participants	0 Participants n=9 Participants	2 Participants n=9 Participants	0 Participants n=15 Participants	3 Participants n=42 Participants
Age, Continuous	49.7 years STANDARD_DEVIATION 10.75 • n=9 Participants	47.2 years STANDARD_DEVIATION 4.63 • n=9 Participants	49.1 years STANDARD_DEVIATION 14.57 • n=9 Participants	46.5 years STANDARD_DEVIATION 11.05 • n=15 Participants	47.9 years STANDARD_DEVIATION 10.57 • n=42 Participants
Sex: Female, Male Female	9 Participants n=9 Participants	8 Participants n=9 Participants	6 Participants n=9 Participants	9 Participants n=15 Participants	32 Participants n=42 Participants
Sex: Female, Male Male	0 Participants n=9 Participants	1 Participants n=9 Participants	3 Participants n=9 Participants	6 Participants n=15 Participants	10 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=9 Participants	2 Participants n=9 Participants	1 Participants n=9 Participants	1 Participants n=15 Participants	5 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=9 Participants	7 Participants n=9 Participants	7 Participants n=9 Participants	14 Participants n=15 Participants	36 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=9 Participants	1 Participants n=9 Participants	0 Participants n=15 Participants	1 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=9 Participants	1 Participants n=9 Participants	0 Participants n=15 Participants	1 Participants n=42 Participants
Race (NIH/OMB) Asian	1 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	3 Participants n=15 Participants	4 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	2 Participants n=9 Participants	1 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=15 Participants	3 Participants n=42 Participants
Race (NIH/OMB) White	6 Participants n=9 Participants	8 Participants n=9 Participants	8 Participants n=9 Participants	12 Participants n=15 Participants	34 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Region of Enrollment United States	9 Participants n=9 Participants	9 Participants n=9 Participants	9 Participants n=9 Participants	15 Participants n=15 Participants	42 Participants n=42 Participants
Baseline Modified Rodnan Skin Score (mRSS)	21.6 units on a scale STANDARD_DEVIATION 9.29 • n=9 Participants	26.7 units on a scale STANDARD_DEVIATION 12.03 • n=9 Participants	22.3 units on a scale STANDARD_DEVIATION 10.16 • n=9 Participants	26.2 units on a scale STANDARD_DEVIATION 11.12 • n=15 Participants	24.5 units on a scale STANDARD_DEVIATION 10.60 • n=42 Participants
Baseline HAQ-DI	1.07 units on a scale STANDARD_DEVIATION 0.745 • n=9 Participants	1.49 units on a scale STANDARD_DEVIATION 0.697 • n=9 Participants	0.83 units on a scale STANDARD_DEVIATION 0.890 • n=9 Participants	1.51 units on a scale STANDARD_DEVIATION 0.793 • n=15 Participants	1.26 units on a scale STANDARD_DEVIATION 0.809 • n=42 Participants
Baseline FVC % Predicted	84.15 percent predicted STANDARD_DEVIATION 9.044 • n=9 Participants • Note: One subject in the Placebo cohort did not have a FVC % predicted measurement conducted, as such, the total number of subjects in the placebo cohort for FVC % predicted is n = 14 and for the total population, n = 41.	93.79 percent predicted STANDARD_DEVIATION 11.740 • n=9 Participants • Note: One subject in the Placebo cohort did not have a FVC % predicted measurement conducted, as such, the total number of subjects in the placebo cohort for FVC % predicted is n = 14 and for the total population, n = 41.	80.10 percent predicted STANDARD_DEVIATION 15.993 • n=9 Participants • Note: One subject in the Placebo cohort did not have a FVC % predicted measurement conducted, as such, the total number of subjects in the placebo cohort for FVC % predicted is n = 14 and for the total population, n = 41.	79.61 percent predicted STANDARD_DEVIATION 10.286 • n=14 Participants • Note: One subject in the Placebo cohort did not have a FVC % predicted measurement conducted, as such, the total number of subjects in the placebo cohort for FVC % predicted is n = 14 and for the total population, n = 41.	84.33 percent predicted STANDARD_DEVIATION 12.185 • n=41 Participants • Note: One subject in the Placebo cohort did not have a FVC % predicted measurement conducted, as such, the total number of subjects in the placebo cohort for FVC % predicted is n = 14 and for the total population, n = 41.

PRIMARY outcome

Timeframe: Part A: Day 113

Population: Per the statistical analysis plan, the intent was to analyze all subjects receiving lenabasum and compare to those subjects receiving placebo for the primary endpoint. As such, individual lenabasum groups were not reported to follow the pre-specified statistical analysis plan.

The overall number of subjects with TEAE's per treatment group during active dosing (Days 1-84) plus the 28 day follow-up.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=15 Participants Placebo BID on Days 1-84.
Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113	17 Participants	9 Participants

PRIMARY outcome

Timeframe: Day 85 and Day 113

Population: Per the statistical analysis plan, the intent was to analyze all subjects receiving lenabasum and compare to those subjects receiving placebo for this endpoint. As such, individual lenabasum groups were not reported to follow the pre-specified statistical analysis plan. Only subjects with values at Visit 5 and 6 were included in this analysis.

CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction \< 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=15 Participants Placebo BID on Days 1-84.
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Day 85 and 113 CRISS score at Visit 5 (Day 85)	0.275 units on a scale Interval 0.0 to 1.0	0.010 units on a scale Interval 0.0 to 1.0
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Day 85 and 113 CRISS score at Visit 6 (Day 113)	0.330 units on a scale Interval 0.0 to 1.0	0.00 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for mRSS total score. Change from Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. The mRSS consists of an evaluation of patient's skin thickness rated by clinical palpation using a 0-3 scale (0 = normal skin; 1 = mild thickness; 2 = moderate thickness; 3 = severe thickness with inability to pinch the skin into a fold for each of 17 surface anatomic areas of the body: face, anterior chest, abdomen, and, with right and left sides of the body separately evaluated, the fingers, forearms, upper arms, thighs, lower legs, dorsum of hands and feet. Individual values are summed and defined as the total skin score. Total score is 0 to 51 with higher scores indicating worse symptomology

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=27 Participants Placebo BID on Days 1-84.
CRISS Individual Components (mRSS Total Score) Change From Baseline. mRSS Total Score CFB at Visit 5 (Day 85)	-2.6 units on a scale Standard Error 1.5	-3.8 units on a scale Standard Error 1.1
CRISS Individual Components (mRSS Total Score) Change From Baseline. mRSS Total Score CFB at Visit 6 (Day 113)	-2.0 units on a scale Standard Error 1.5	-4.7 units on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for FVC percent predicted. Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=27 Participants Placebo BID on Days 1-84.
CRISS Individual Component (FVC Percent Predicted) Change From Baseline FVC % predicted CFB at Visit 5 (Day 85)	-0.77 percent predicted Standard Deviation 1.32	0.90 percent predicted Standard Deviation 0.99
CRISS Individual Component (FVC Percent Predicted) Change From Baseline FVC % predicted CFB at Visit 6 (Day 113)	-0.98 percent predicted Standard Deviation 1.22	0.20 percent predicted Standard Deviation 0.92

SECONDARY outcome

Timeframe: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for physician global assessment. Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. The Physician Global Assessment of disease activity will be performed using a segmented numerical version of the visual analogue scale in which the physician selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by 2 verbal descriptors, one of "no disease activity" (score of 0) and one of "worse imaginable disease activity" (score of 10), with numbers 1-9 spaced equidistance in between. The physician will select an integer to describe disease activity. The recall period is one week.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=27 Participants Placebo BID on Days 1-84.
CRISS Individual Component (Physician Global Assessment Score) Change From Baseline Physician Global Assessment Score CFB at Visit 5	-0.5 units on a scale Standard Deviation 0.4	-0.9 units on a scale Standard Deviation 0.3
CRISS Individual Component (Physician Global Assessment Score) Change From Baseline Physician Global Assessment Score CFB at Visit 6	-0.7 units on a scale Standard Deviation 0.3	-0.9 units on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for patient global assessment. Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. The assessment at each specified visit will be performed with a segmented numerical version of the visual analogue scale in which the subject selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by two verbal descriptors, one of "no disease activity" (score of 0) and one of "worse imaginable disease activity" (score of 10), with numbers 1-9 spaced equidistance in between. The subject will select an integer to describe disease activity. The recall period is one week.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=27 Participants Placebo BID on Days 1-84.
CRISS Individual Component (Patient Global Assessment Score) Change From Baseline Patient Global Assessment Score CFB at Visit 5	0.4 units on a scale Standard Deviation 0.6	-0.8 units on a scale Standard Deviation 0.4
CRISS Individual Component (Patient Global Assessment Score) Change From Baseline Patient Global Assessment Score CFB at Visit 6	0.3 units on a scale Standard Deviation 0.5	-0.9 units on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: Day 85 and 113

Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. Health Assessment Questionnaire - Disability Index includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are two or three questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The eight scores of the eight sections are summed and divided by 8. If one section is not completed by a subject, the summed score is divided by 7. As such, maximum scores can vary with a min of 0. The result is the DI, the disability index or functional disability index. Higher scores indicate worse symptomology

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Placebo subjects in this study received placebo for the entire duration of the trial.	Placebo n=27 Participants Placebo BID on Days 1-84.
CRISS Individual Component (HAQ-DI Score) Change From Baseline. HAQ-DI CFB at Visit 5 (Day 85)	0.11 units on a scale Standard Deviation 0.10	-0.22 units on a scale Standard Deviation 0.07
CRISS Individual Component (HAQ-DI Score) Change From Baseline. HAQ-DI CFB at Visit 6 (Day 113)	0.11 units on a scale Standard Deviation 0.09	-0.14 units on a scale Standard Deviation 0.07

Adverse Events

Placebo (Days 1 - 84 + After-treatment Period)

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Combined Lenabasum (Days 1 - 84 + After-treatment Period)

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (Days 1 - 84 + After-treatment Period) n=15 participants at risk Placebo cohort for the overall study.	Combined Lenabasum (Days 1 - 84 + After-treatment Period) n=27 participants at risk Combined lenabasum cohorts for the overall study.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Days 1 - 113 Lenabasum (JBT-101) 5 mg QD/20 mg BID, Lenabasum (JBT-101) 20 mg QD/20 mg BID, and Lenabasum (JBT-101) 20 mg BID/20 mg BID Groups were combined (i.e., Combined Lenabasum) as pre-specified in the study protocol.	3.7% 1/27 • Days 1 - 113 Lenabasum (JBT-101) 5 mg QD/20 mg BID, Lenabasum (JBT-101) 20 mg QD/20 mg BID, and Lenabasum (JBT-101) 20 mg BID/20 mg BID Groups were combined (i.e., Combined Lenabasum) as pre-specified in the study protocol.
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Days 1 - 113 Lenabasum (JBT-101) 5 mg QD/20 mg BID, Lenabasum (JBT-101) 20 mg QD/20 mg BID, and Lenabasum (JBT-101) 20 mg BID/20 mg BID Groups were combined (i.e., Combined Lenabasum) as pre-specified in the study protocol.	0.00% 0/27 • Days 1 - 113 Lenabasum (JBT-101) 5 mg QD/20 mg BID, Lenabasum (JBT-101) 20 mg QD/20 mg BID, and Lenabasum (JBT-101) 20 mg BID/20 mg BID Groups were combined (i.e., Combined Lenabasum) as pre-specified in the study protocol.

Other adverse events

Additional Information

John Skutnik, MS

Corbus Pharmaceuticals, Inc.

Phone: 781-562-9853

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place