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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 : Terminated (Sponsor terminated open-label extension)
First Posted : June 8, 2015
Results First Posted : October 2, 2018
Last Update Posted : April 21, 2021
Sponsor:
Information provided by (Responsible Party):
Corbus Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE June 4, 2015
First Posted Date  ICMJE June 8, 2015
Results First Submitted Date  ICMJE March 8, 2018
Results First Posted Date  ICMJE October 2, 2018
Last Update Posted Date April 21, 2021
Study Start Date  ICMJE August 2015
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
  • Number of participants with treatment-emergent adverse events from baseline at Day 113 [ Time Frame: 112 days, with 84 days treatment and 28 days follow-up ]
  • Change in Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) from baseline at Day 85 [ Time Frame: 84 days treatment period ]
    CRISS responders and its domains of modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • 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
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
  • Change in patient-reported outcomes from baseline at Day 85 [ Time Frame: 84 days treatment period ]
    National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Short Form, the PROMIS-29 Short Form single item pain numerical rating score, the 5-D Itch Score, and a Systemic Sclerosis Skin Questionnaire
  • Change in JBT-101 plasma concentrations from baseline at Day 85 [ Time Frame: 84 days treatment period ]
  • Change in metabolipidomic profile from baseline at Day 85 [ Time Frame: 84 days treatment period ]
  • Change in blood biomarkers of disease activity, inflammation and fibrosis from baseline at Day 85 [ Time Frame: 84 days treatment period ]
  • Change in skin biomarkers of inflammation and fibrosis from baseline at Day 85 [ Time Frame: 84 days treatment period ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Cutaneous Systemic Sclerosis
Intervention  ICMJE
  • 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.
  • Drug: Part B Open-Label Extension
    JBT-101 20mg bid on Days 1-364
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: JBT-101
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: JBT-101
    • Drug: Placebo
  • Experimental: JBT-101 20 mg bid/20 mg bid
    JBT-101 20 mg bid on Days 1-84.
    Intervention: Drug: JBT-101
  • Placebo Comparator: Placebo
    Placebo bid on Days 1-84.
    Intervention: Drug: Placebo
  • Experimental: Part B Open-label
    JBT-101 20 mg bid on Days 1-364
    Intervention: Drug: Part B Open-Label Extension
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 17, 2016)
42
Original Estimated Enrollment  ICMJE
 (submitted: June 4, 2015)
36
Actual Study Completion Date  ICMJE December 11, 2020
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02465437
Other Study ID Numbers  ICMJE JBT101-SSc-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Corbus Pharmaceuticals Inc.
Study Sponsor  ICMJE Corbus Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robert Spiera, M.D. Weill Cornell Medical College, New York City, NY
PRS Account Corbus Pharmaceuticals Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP