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
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Sponsor
- Corbus Pharmaceuticals Inc.
- Enrollment
- 42
- Locations
- 9
- Primary Endpoint
- Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 ≥
- •Stable treatment for SSc for at least 28 days before Visit 1
- •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);
Exclusion Criteria
- Not provided
Arms & Interventions
Placebo
Placebo bid on Days 1-84.
Intervention: Placebo
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.
Intervention: JBT-101
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.
Intervention: Placebo
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.
Intervention: JBT-101
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.
Intervention: Placebo
JBT-101 20 mg bid/20 mg bid
JBT-101 20 mg bid on Days 1-84.
Intervention: JBT-101
Part B Open-label
JBT-101 20 mg bid on Days 1-364
Intervention: Part B Open-Label Extension
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- CRISS Individual Component (Patient Global Assessment Score) Change From Baseline(Day 85 and 113)
- CRISS Individual Components (mRSS Total Score) Change From Baseline.(Day 85 and 113)
- CRISS Individual Component (Physician Global Assessment Score) Change From Baseline(Day 85 and 113)
- CRISS Individual Component (HAQ-DI Score) Change From Baseline.(Day 85 and 113)
- CRISS Individual Component (FVC Percent Predicted) Change From Baseline(Day 85 and 113)