Back to resultsSafety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis
Primary Purpose
Diffuse Cutaneous Systemic Sclerosis
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
JBT-101
Placebo
Part B Open-Label Extension
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Cutaneous Systemic Sclerosis focused on measuring JBT-101, Lenabasum, Systemic Sclerosis
Eligibility Criteria
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:
- A positive pregnancy test (or at Visit 1);
- Hemoglobin < 10 g/dL
- Neutrophils < 1.0 x 10^9/L
- Platelets < 75 x 10^9/L
- Creatinine clearance < 50 ml/min according to modified Cockcroft-Gault equation
- Serum transaminases > 2.0 x upper normal limit
- 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.
Sites / Locations
- Arthritis Association of Southern CA
- Stanford University
- John Hopkins Scleroderma Center
- Boston University Medical Center
- Rutgers University
- Weill Cornell Medical College
- University of Pittsburgh Medical Center
- University of Texas Houston Medical School
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
JBT-101 5 mg/20 mg bid
JBT-101 20 mg/20 mg bid
JBT-101 20 mg bid/20 mg bid
Placebo
Part B Open-label
Arm Description
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.
JBT-101 20 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg bid on Days 29-84.
JBT-101 20 mg bid on Days 1-84.
Placebo bid on Days 1-84.
JBT-101 20 mg bid on Days 1-364
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events From Baseline at 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.
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Day 85 and 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
CRISS Individual Components (mRSS Total Score) Change From Baseline.
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
CRISS Individual Component (FVC Percent Predicted) Change From Baseline
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.
CRISS Individual Component (Physician Global Assessment Score) Change From Baseline
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.
CRISS Individual Component (Patient Global Assessment Score) Change From Baseline
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.
CRISS Individual Component (HAQ-DI Score) Change From Baseline.
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
Full Information
NCT ID
NCT02465437
First Posted
June 4, 2015
Last Updated
March 25, 2021
Sponsor
Corbus Pharmaceuticals Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02465437
Brief Title
Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis
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 Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Sponsor terminated open-label extension
Study Start Date
August 2015 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
December 11, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Corbus Pharmaceuticals Inc.
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Cutaneous Systemic Sclerosis
Keywords
JBT-101, Lenabasum, Systemic Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
JBT-101 5 mg/20 mg bid
Arm Type
Experimental
Arm Description
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.
Arm Title
JBT-101 20 mg/20 mg bid
Arm Type
Experimental
Arm Description
JBT-101 20 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg bid on Days 29-84.
Arm Title
JBT-101 20 mg bid/20 mg bid
Arm Type
Experimental
Arm Description
JBT-101 20 mg bid on Days 1-84.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo bid on Days 1-84.
Arm Title
Part B Open-label
Arm Type
Experimental
Arm Description
JBT-101 20 mg bid on Days 1-364
Intervention Type
Drug
Intervention Name(s)
JBT-101
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Part B Open-Label Extension
Intervention Description
JBT-101 20mg bid on Days 1-364
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
A positive pregnancy test (or at Visit 1);
Hemoglobin < 10 g/dL
Neutrophils < 1.0 x 10^9/L
Platelets < 75 x 10^9/L
Creatinine clearance < 50 ml/min according to modified Cockcroft-Gault equation
Serum transaminases > 2.0 x upper normal limit
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Spiera, M.D.
Organizational Affiliation
Weill Cornell Medical College, New York City, NY
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arthritis Association of Southern CA
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
Country
United States
Facility Name
John Hopkins Scleroderma Center
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Rutgers University
City
New Brunswick
State/Province
New Jersey
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
University of Texas Houston Medical School
City
Houston
State/Province
Texas
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis
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