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

• ClinicalTrials.gov Identifier: NCT02465437
• Recruitment Status: Terminated
• First Posted: June 8, 2015
• Results First Posted: October 2, 2018
• Last Update Posted: April 21, 2021
• Sponsor: Corbus Pharmaceuticals Inc.
• Information provided by (Responsible Party): Corbus Pharmaceuticals Inc.

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 (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
• Actual Study Completion Date: December 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 [ 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

Eligibility Criteria

• 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.

Contacts and Locations

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

More Information

• Responsible Party: Corbus Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT02465437
• Other Study ID Numbers: JBT101-SSc-001
• First Posted: June 8, 2015
• Results First Posted: October 2, 2018
• Last Update Posted: April 21, 2021
• Last Verified: March 2021

Keywords provided by Corbus Pharmaceuticals Inc.:

JBT-101, Lenabasum, Systemic Sclerosis

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases