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

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ClinicalTrials.gov Identifier: NCT02465437
Recruitment Status : Active, not recruiting
First Posted : June 8, 2015
Results First Posted : October 2, 2018
Last Update Posted : October 2, 2018
Sponsor:
Information provided by (Responsible Party):
Corbus Pharmaceuticals Inc.

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 Type : Interventional  (Clinical Trial)
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 : August 2015
Actual Primary Completion Date : October 2016
Estimated Study Completion Date : October 2018


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




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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



Information from the National Library of Medicine

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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

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.

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): NCT02465437


Locations
United States, California
Arthritis Association of Southern CA
Los Angeles, California, United States
Stanford University
Palo Alto, California, United States
United States, Maryland
John Hopkins Scleroderma Center
Baltimore, Maryland, United States
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States
United States, New Jersey
Rutgers University
New Brunswick, New Jersey, United States
United States, New York
Weill Cornell Medical College
New York, New York, United States
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
United States, Texas
University of Texas Houston Medical School
Houston, Texas, United States
United States, Utah
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

Responsible Party: Corbus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02465437     History of Changes
Other Study ID Numbers: JBT101-SSc-001
First Posted: June 8, 2015    Key Record Dates
Results First Posted: October 2, 2018
Last Update Posted: October 2, 2018
Last Verified: October 2018

Keywords provided by Corbus Pharmaceuticals Inc.:
JBT-101, Lenabasum, Systemic Sclerosis

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases