Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis

• Sponsor: Corbus Pharmaceuticals Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02465437
• Collaborator: (none)
• Enrollment: 42
• Locations: 9
• Arms: 5
• Duration (Months): 64.4
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of JBT-101 in adult subjects with diffuse cutaneous systemic sclerosis.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Cutaneous Systemic Sclerosis	Drug: JBT-101; Drug: Placebo; Drug: Part B Open-Label Extension	Phase 2

Detailed Description

Part A of the study is an interventional, double-blind, randomized, placebo-control design will be used to test safety, tolerability, pharmacokinetics, and efficacy of JBT-101 in subjects ≥ 18 and ≤ 70 years of age with active diffuse cutaneous systemic sclerosis. The screening period is up to 28 days, with 84 days treatment period and 28 days follow-up off active treatment.

Part B of the study is an interventional, open-label design will be used. All subjects who complete dosing in Part A without permanent discontinuation of study drug and who pass repeat safety screening will be eligible for enrollment. The screening period is up to 28 days, with a 364 day treatment period and 28 day follow up after last dose of JBT-101.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to Evaluate Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Diffuse Cutaneous Systemic Sclerosis
• Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Dec 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JBT-101 5 mg/20 mg bid JBT-101 5 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg twice a day (bid) on Days 29-84.	Drug: JBT-101; JBT-101 5 mg q am, 20 mg q am, or 20 mg bid on Days 1-28. JBT-101 20 mg bid on Days 29-84.; Drug: Placebo; Placebo q pm (with JBT-101 5 or 20 mg q AM) or placebo bid on Days 1-28. Placebo bid on Days 29-84.
Experimental: JBT-101 20 mg/20 mg bid JBT-101 20 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg bid on Days 29-84.	Drug: JBT-101; JBT-101 5 mg q am, 20 mg q am, or 20 mg bid on Days 1-28. JBT-101 20 mg bid on Days 29-84.; Drug: Placebo; Placebo q pm (with JBT-101 5 or 20 mg q AM) or placebo bid on Days 1-28. Placebo bid on Days 29-84.
Experimental: JBT-101 20 mg bid/20 mg bid JBT-101 20 mg bid on Days 1-84.	Drug: JBT-101; JBT-101 5 mg q am, 20 mg q am, or 20 mg bid on Days 1-28. JBT-101 20 mg bid on Days 29-84.
Placebo Comparator: Placebo Placebo bid on Days 1-84.	Drug: Placebo; Placebo q pm (with JBT-101 5 or 20 mg q AM) or placebo bid on Days 1-28. Placebo bid on Days 29-84.
Experimental: Part B Open-label JBT-101 20 mg bid on Days 1-364	Drug: Part B Open-Label Extension; JBT-101 20mg bid on Days 1-364

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113 [Part A: Day 113]

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

2. Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Day 85 and 113 [Day 85 and Day 113]

   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.

Secondary Outcome Measures

1. CRISS Individual Components (mRSS Total Score) Change From Baseline. [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

2. CRISS Individual Component (FVC Percent Predicted) Change From Baseline [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.

3. CRISS Individual Component (Physician Global Assessment Score) Change From Baseline [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.

4. CRISS Individual Component (Patient Global Assessment Score) Change From Baseline [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.

5. CRISS Individual Component (HAQ-DI Score) Change From Baseline. [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Part A

• Diffuse cutaneous systemic sclerosis

• Have skin thickening from SSc in a body area suitable for repeat biopsy

• Disease duration ≤ 3 years from the first non-Raynaud's phenomenon or >3 years and ≤ 6 years from the first non-Raynaud's phenomenon and high sensitivity C-reactive protein

3 mg/L, high sensitivity interleukin-6 > 5 pg/mL, or increase in mRSS ≥ 5 points over the last 6 months with total RSS ≥ 12.

• Stable treatment for SSc for at least 28 days before Visit 1

Part B

•Completion of dosing in Part A without permanent discontinuation of study product because of safety or tolerability reasons.

Exclusion Criteria (Part A and B):

• Severe or unstable systemic sclerosis

• Significant diseases or conditions other than systemic sclerosis that may influence response to the study product or safety;

• Any one of the following values for laboratory tests at Screening:

1. A positive pregnancy test (or at Visit 1);

2. Hemoglobin < 10 g/dL

3. Neutrophils < 1.0 x 10^9/L

4. Platelets < 75 x 10^9/L

5. Creatinine clearance < 50 ml/min according to modified Cockcroft-Gault equation

6. Serum transaminases > 2.0 x upper normal limit

7. Total bilirubin ≥ 1.5 x upper limit of normal

• Any other condition that, in the opinion of the Principal Investigator, is clinically significant and may put the subject at greater safety risk, influence response to study product, or interfere with study assessments.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arthritis Association of Southern CA	Los Angeles	California	United States
2	Stanford University	Palo Alto	California	United States
3	John Hopkins Scleroderma Center	Baltimore	Maryland	United States
4	Boston University Medical Center	Boston	Massachusetts	United States
5	Rutgers University	New Brunswick	New Jersey	United States
6	Weill Cornell Medical College	New York	New York	United States
7	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States
8	University of Texas Houston Medical School	Houston	Texas	United States
9	University of Utah	Salt Lake City	Utah	United States

Sponsors and Collaborators

• Corbus Pharmaceuticals Inc.

Investigators

• Principal Investigator: Robert Spiera, M.D., Weill Cornell Medical College, New York City, NY

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Corbus Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT02465437
• Other Study ID Numbers: JBT101-SSc-001
• First Posted: Jun 8, 2015
• Last Update Posted: Apr 21, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Corbus Pharmaceuticals Inc.: JBT-101, Lenabasum, Systemic Sclerosis
• Additional relevant MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	Lenabasum (JBT-101) 5 mg QD/20 mg BID	Lenabasum (JBT-101) 20 mg QD/20 mg BID	Lenabasum (JBT-101) 20 mg BID/20 mg BID	Placebo	Total
Arm/Group Description	Lenabasum 5 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum 20 mg QAM and placebo QPM on Days 1-28, then lenabasum 20 mg BID on Days 29-84.	Lenabasum 20 mg BID on Days 1-84.	Placebo BID on Days 1-84.	Total of all reporting groups
Overall Participants	9	9	9	15	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 88.9%	9 100%	7 77.8%	15 100%	39 92.9%
>=65 years	1 11.1%	0 0%	2 22.2%	0 0%	3 7.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.7 (10.75)	47.2 (4.63)	49.1 (14.57)	46.5 (11.05)	47.9 (10.57)
Sex: Female, Male (Count of Participants)
Female	9 100%	8 88.9%	6 66.7%	9 60%	32 76.2%
Male	0 0%	1 11.1%	3 33.3%	6 40%	10 23.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 11.1%	2 22.2%	1 11.1%	1 6.7%	5 11.9%
Not Hispanic or Latino	8 88.9%	7 77.8%	7 77.8%	14 93.3%	36 85.7%
Unknown or Not Reported	0 0%	0 0%	1 11.1%	0 0%	1 2.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 11.1%	0 0%	1 2.4%
Asian	1 11.1%	0 0%	0 0%	3 20%	4 9.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 22.2%	1 11.1%	0 0%	0 0%	3 7.1%
White	6 66.7%	8 88.9%	8 88.9%	12 80%	34 81%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	9 100%	9 100%	9 100%	15 100%	42 100%
Baseline Modified Rodnan Skin Score (mRSS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.6 (9.29)	26.7 (12.03)	22.3 (10.16)	26.2 (11.12)	24.5 (10.60)
Baseline HAQ-DI (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.07 (0.745)	1.49 (0.697)	0.83 (0.890)	1.51 (0.793)	1.26 (0.809)
Baseline FVC % Predicted (percent predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent predicted]	84.15 (9.044)	93.79 (11.740)	80.10 (15.993)	79.61 (10.286)	84.33 (12.185)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113
Description	The overall number of subjects with TEAE's per treatment group during active dosing (Days 1-84) plus the 28 day follow-up.
Time Frame	Part A: Day 113

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Combined Lenabasum Group
Arm/Group Description	Placebo BID on Days 1-84.	Combination of all lenabasum cohorts for analysis purposes only.
Measure Participants	15	27
Count of Participants [Participants]	9 100%	17 188.9%

2. Primary Outcome

Title	Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Day 85 and 113
Description	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.
Time Frame	Day 85 and Day 113

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Combined Lenabasum Group
Arm/Group Description	Placebo BID on Days 1-84.	Combination of all lenabasum cohorts for analysis purposes only.
Measure Participants	15	26
CRISS score at Visit 5 (Day 85)	0.010	0.275
CRISS score at Visit 6 (Day 113)	0.00	0.330

3. Secondary Outcome

Title	CRISS Individual Components (mRSS Total Score) Change From Baseline.
Description	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
Time Frame	Day 85 and 113

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Lenabasum Cohorts	Placebo
Arm/Group Description	This analysis group combines data from lenabasum Cohort 1 (5 mg QD/20mg BID), Cohort 2 (20 mg QD/20 mg BID), and Cohort 3 (20 mg BID/20 mg BID) for analysis purposes only.	Placebo subjects in this study received placebo for the entire duration of the trial.
Measure Participants	27	15
mRSS Total Score CFB at Visit 5 (Day 85)	-3.8 (1.1)	-2.6 (1.5)
mRSS Total Score CFB at Visit 6 (Day 113)	-4.7 (1.1)	-2.0 (1.5)

4. Secondary Outcome

Title	CRISS Individual Component (FVC Percent Predicted) Change From Baseline
Description	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.
Time Frame	Day 85 and 113

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Lenabasum Cohorts	Placebo
Arm/Group Description	This analysis group combines data from lenabasum Cohort 1 (5 mg QD/20mg BID), Cohort 2 (20 mg QD/20 mg BID), and Cohort 3 (20 mg BID/20 mg BID) for analysis purposes only.	Placebo subjects in this study received placebo for the entire duration of the trial.
Measure Participants	27	15
FVC % predicted CFB at Visit 5 (Day 85)	0.90 (0.99)	-0.77 (1.32)
FVC % predicted CFB at Visit 6 (Day 113)	0.20 (0.92)	-0.98 (1.22)

5. Secondary Outcome

Title	CRISS Individual Component (Physician Global Assessment Score) Change From Baseline
Description	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.
Time Frame	Day 85 and 113

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Lenabasum Cohorts	Placebo
Arm/Group Description	This analysis group combines data from lenabasum Cohort 1 (5 mg QD/20mg BID), Cohort 2 (20 mg QD/20 mg BID), and Cohort 3 (20 mg BID/20 mg BID) for analysis purposes only.	Placebo subjects in this study received placebo for the entire duration of the trial.
Measure Participants	27	15
Physician Global Assessment Score CFB at Visit 5	-0.9 (0.3)	-0.5 (0.4)
Physician Global Assessment Score CFB at Visit 6	-0.9 (0.3)	-0.7 (0.3)

6. Secondary Outcome

Title	CRISS Individual Component (Patient Global Assessment Score) Change From Baseline
Description	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.
Time Frame	Day 85 and 113

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Lenabasum Cohorts	Placebo
Arm/Group Description	This analysis group combines data from lenabasum Cohort 1 (5 mg QD/20mg BID), Cohort 2 (20 mg QD/20 mg BID), and Cohort 3 (20 mg BID/20 mg BID) for analysis purposes only.	Placebo subjects in this study received placebo for the entire duration of the trial.
Measure Participants	27	15
Patient Global Assessment Score CFB at Visit 5	-0.8 (0.4)	0.4 (0.6)
Patient Global Assessment Score CFB at Visit 6	-0.9 (0.4)	0.3 (0.5)

7. Secondary Outcome

Title	CRISS Individual Component (HAQ-DI Score) Change From Baseline.
Description	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
Time Frame	Day 85 and 113

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Lenabasum Cohorts	Placebo
Arm/Group Description	This analysis group combines data from lenabasum Cohort 1 (5 mg QD/20mg BID), Cohort 2 (20 mg QD/20 mg BID), and Cohort 3 (20 mg BID/20 mg BID) for analysis purposes only.	Placebo subjects in this study received placebo for the entire duration of the trial.
Measure Participants	27	15
HAQ-DI CFB at Visit 5 (Day 85)	-0.22 (0.07)	0.11 (0.10)
HAQ-DI CFB at Visit 6 (Day 113)	-0.14 (0.07)	0.11 (0.09)

Adverse Events

Time Frame	Days 1 - 113
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo (Days 1 - 84 + After-treatment Period)		Combined Lenabasum (Days 1 - 84 + After-treatment Period)
Arm/Group Description	Placebo cohort for the overall study.		Combined lenabasum cohorts for the overall study.
All Cause Mortality
	Placebo (Days 1 - 84 + After-treatment Period)		Combined Lenabasum (Days 1 - 84 + After-treatment Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/27 (0%)
Serious Adverse Events
	Placebo (Days 1 - 84 + After-treatment Period)		Combined Lenabasum (Days 1 - 84 + After-treatment Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		1/27 (3.7%)
Gastrointestinal disorders
Vomiting	0/15 (0%)		1/27 (3.7%)
Abdominal pain	1/15 (6.7%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Placebo (Days 1 - 84 + After-treatment Period)		Combined Lenabasum (Days 1 - 84 + After-treatment Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/15 (60%)		17/27 (63%)
Eye disorders
Vision blurred	1/15 (6.7%)		0/27 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/15 (0%)		1/27 (3.7%)
Constipation	0/15 (0%)		1/27 (3.7%)
Diarrhoea	0/15 (0%)		2/27 (7.4%)
Dry mouth	1/15 (6.7%)		0/27 (0%)
Dyspepsia	1/15 (6.7%)		0/27 (0%)
Mouth ulceration	0/15 (0%)		1/27 (3.7%)
Nausea	2/15 (13.3%)		1/27 (3.7%)
Stomatitis	0/15 (0%)		1/27 (3.7%)
General disorders
Face oedema	0/15 (0%)		1/27 (3.7%)
Fatigue	1/15 (6.7%)		5/27 (18.5%)
Feeling abnormal	0/15 (0%)		1/27 (3.7%)
Oedema peripheral	0/15 (0%)		1/27 (3.7%)
Pain	0/15 (0%)		1/27 (3.7%)
Pyrexia	0/15 (0%)		1/27 (3.7%)
Infections and infestations
Herpes simplex	0/15 (0%)		1/27 (3.7%)
Herpes zoster	1/15 (6.7%)		0/27 (0%)
Infected skin ulcer	1/15 (6.7%)		0/27 (0%)
Nasopharyngitis	0/15 (0%)		1/27 (3.7%)
Oral herpes	0/15 (0%)		1/27 (3.7%)
Sinusitis	0/15 (0%)		1/27 (3.7%)
Small intestinal bacterial overgrowth	1/15 (6.7%)		0/27 (0%)
Upper respiratory tract infection	0/15 (0%)		3/27 (11.1%)
Urinary tract infection	1/15 (6.7%)		2/27 (7.4%)
Injury, poisoning and procedural complications
Concussion	1/15 (6.7%)		0/27 (0%)
Post-traumatic pain	1/15 (6.7%)		0/27 (0%)
Investigations
Alanine aminotransferase increased	1/15 (6.7%)		0/27 (0%)
Forced vital capacity decreased	2/15 (13.3%)		0/27 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)		3/27 (11.1%)
Back pain	1/15 (6.7%)		0/27 (0%)
Joint stiffness	0/15 (0%)		1/27 (3.7%)
Joint swelling	0/15 (0%)		1/27 (3.7%)
Muscle spasms	0/15 (0%)		1/27 (3.7%)
Musculoskeletal pain	0/15 (0%)		1/27 (3.7%)
Pain in extremity	1/15 (6.7%)		1/27 (3.7%)
Rheumatoid arthritis	0/15 (0%)		1/27 (3.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm	0/15 (0%)		1/27 (3.7%)
Nervous system disorders
Disturbance in attention	0/15 (0%)		1/27 (3.7%)
Dizziness	2/15 (13.3%)		6/27 (22.2%)
Headache	1/15 (6.7%)		3/27 (11.1%)
Hypoaesthesia	0/15 (0%)		1/27 (3.7%)
Nervous system disorder	0/15 (0%)		1/27 (3.7%)
Paraesthesia	0/15 (0%)		1/27 (3.7%)
Radiculopathy	1/15 (6.7%)		0/27 (0%)
Somnolence	1/15 (6.7%)		0/27 (0%)
Psychiatric disorders
Anxiety	0/15 (0%)		1/27 (3.7%)
Bradyphrenia	0/15 (0%)		1/27 (3.7%)
Dysphoria	0/15 (0%)		1/27 (3.7%)
Initial insomnia	0/15 (0%)		1/27 (3.7%)
Insomnia	1/15 (6.7%)		0/27 (0%)
Paranoia	0/15 (0%)		1/27 (3.7%)
Restlessness	1/15 (6.7%)		0/27 (0%)
Renal and urinary disorders
Dysuria	0/15 (0%)		1/27 (3.7%)
Skin and subcutaneous tissue disorders
Pruritus	0/15 (0%)		1/27 (3.7%)
Pruritus generalized	1/15 (6.7%)		0/27 (0%)
Rash	1/15 (6.7%)		0/27 (0%)
Rash pruritic	0/15 (0%)		1/27 (3.7%)
Skin lesion	0/15 (0%)		1/27 (3.7%)
Uticaria	1/15 (6.7%)		0/27 (0%)
Vascular disorders
Hypotension	0/15 (0%)		1/27 (3.7%)
Peripheral ischemia	0/15 (0%)		1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.