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

Phase 2

Terminated

• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Interventions: Drug: Part B Open-Label Extension; Drug: JBT-101; Drug: Placebo

• Registration Number: NCT02465437
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2015-06-04
• Study First Submitted QC: 2015-06-04
• Study First Posted: 2015-06-08
• Study Start: 2015-08
• Primary Completion: 2016-10
• Results First Submitted: 2018-03-08
• Results First Submitted QC: 2018-10-01
• Results First Posted: 2018-10-02
• Study Completion: 2020-12-11
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-25
• Last Update Posted: 2021-04-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 42

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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
JBT-101 20 mg/20 mg bid	Placebo	JBT-101 20 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg bid on Days 29-84.
Part B Open-label	Part B Open-Label Extension	JBT-101 20 mg bid on Days 1-364
JBT-101 5 mg/20 mg bid	JBT-101	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.
Placebo	Placebo	Placebo bid on Days 1-84.
JBT-101 5 mg/20 mg bid	Placebo	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/20 mg bid	JBT-101	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/20 mg bid	JBT-101	JBT-101 20 mg bid on Days 1-84.

Primary Outcome Measures

Name	Time	Method
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.
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

Name	Time	Method
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.
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
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.
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
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.

Trial Locations

Locations (9)

Arthritis Association of Southern CA; 🇺🇸 Los Angeles, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

John Hopkins Scleroderma Center; 🇺🇸 Baltimore, Maryland, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Rutgers University; 🇺🇸 New Brunswick, New Jersey, United States

Boston University Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas Houston Medical School; 🇺🇸 Houston, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States