Dermatomyositis
Conditions
Keywords
JBT-101, lenabasum, dermatomyositis
Brief summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of JBT-101 in adult subjects with skin-predominant, dermatomyositis (DM) that is refractory to at least 3 months treatment with hydroxychloroquine.
Detailed description
Part A: An interventional, double-blind, randomized, placebo-control design will be used to test JBT-101 in about 22 eligible male or female subjects ≥ 18 and ≤ 70 years of age with moderate-to-severe active skin-predominant dermatomyositis. Part B: A one-year open-label design to test JBT-101 in subjects who completed Part A without permanent discontinuation of study product because of safety or tolerability reasons.
Interventions
DRUGJBT-101
Part A: 20 mg once daily on Days 1-28, then 20 mg twice daily on Days 29-84. Part B: JBT-101 20 mg twice daily on Days 1 - 365 of the OLE.
DRUGPlacebo
Part A: Once daily on Days 1-28, then twice daily on Days 29-84. Part B: Placebo twice daily on Days 1 - 365 of the OLE.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Pennsylvania
Corbus Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
(Part A): * CDASI activity score ≥ 14; * No difficulty with lifting or walking, and no more than 1.5 x the upper limit of normal of creatine phosphokinase or aldolase; * Failed at least 3 months treatment with hydroxychloroquine; * Stable treatment for dermatomyositis for at least 28 days before Visit 1 (Day 1). Inclusion Criteria (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): * Significant diseases or conditions other than DM 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. Aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase \> 2.5 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) From Baseline in Part A. | Part A: 84-day treatment period (Change from the Baseline CDSAI score at Day 84) | The CDASI is a validated outcome measure that systematically quantifies cutaneous DM disease activity, In the CDASI, DM skin disease activity is scored from 0 to 100 based on the physician's evaluation of erythema, scale, and erosion or ulceration at 15 anatomic locations as well as alopecia, Gottron's sign or papules on the hands, and periungual changes. A 5-point or greater decrease in the CDASI activity score indicates clinically relevant improvement based on statistical analysis using a receiver operating characteristic curve to maximize sensitivity and specificity |
| Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Part A: to Day 84 | Number of participants with treatment emergent adverse events were assessed as a measure of safety and tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient-reported Outcomes From Baseline at 84 Days for Part A | Part A: 84-day treatment period | LS mean (SE) change from baseline to Week 6 (Day 84) for lenabasum vs. placebo using a mixed model repeated measures analysis The CDASI is a validated outcome measure that systematically quantifies cutaneous DM disease activity and damage, In the CDASI, the Damage Score is scored from 0 to 32 based on the physician's evaluation of poikiloderma and calcinosis. 0 representing no damage and 32 representing the greatest level of damage. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| JBT-101 Part A: JBT-101 20 mg capsule once a day on Days 1-28, then 20 mg capsule twice a day on Days 29-84.
Part B: JBT-101 20 mg twice daily on Days 1 - 365 of the OLE.
JBT-101: Part A: 20 mg once daily on Days 1-28, then 20 mg twice daily on Days 29-84.
Part B: JBT-101 20 mg twice daily on Days 1 - 365 of the OLE. | 11 |
| Placebo Part A: Placebo capsule once a day on Days 1-28, then placebo capsule twice a day on Days 29-84.
Part B: Placebo twice daily on Days 1 - 365 of the OLE.
Placebo: Part A: Once daily on Days 1-28, then twice daily on Days 29-84.
Part B: Placebo twice daily on Days 1 - 365 of the OLE. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part B Open-label Treatment Period | Adverse Event | 1 | 0 |
| Part B Open-label Treatment Period | Missing | 2 | 2 |
| Part B Open-label Treatment Period | Sponsor Decision | 8 | 6 |
| Part B Open-label Treatment Period | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | JBT-101 |
|---|---|---|---|
| Age, Continuous | 52.5 years STANDARD_DEVIATION 10.44 | 52.8 years STANDARD_DEVIATION 9.66 | 53.1 years STANDARD_DEVIATION 9.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 19 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race White | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 11 / 11 | 11 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) From Baseline in Part A.
The CDASI is a validated outcome measure that systematically quantifies cutaneous DM disease activity, In the CDASI, DM skin disease activity is scored from 0 to 100 based on the physician's evaluation of erythema, scale, and erosion or ulceration at 15 anatomic locations as well as alopecia, Gottron's sign or papules on the hands, and periungual changes. A 5-point or greater decrease in the CDASI activity score indicates clinically relevant improvement based on statistical analysis using a receiver operating characteristic curve to maximize sensitivity and specificity
Time frame: Part A: 84-day treatment period (Change from the Baseline CDSAI score at Day 84)
Population: modified intent-to-treat population LS mean (SE) at Day 84
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lenabasum | Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) From Baseline in Part A. | -8.0 CDASI Activity Score | Standard Error 8.16 |
| Placebo | Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) From Baseline in Part A. | -5.5 CDASI Activity Score | Standard Error 5.56 |
Primary
Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability
Number of participants with treatment emergent adverse events were assessed as a measure of safety and tolerability
Time frame: Part A: to Day 84
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lenabasum | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any TEAE leading to discontinuation | 0 Participants |
| Lenabasum | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any severe TEAE | 0 Participants |
| Lenabasum | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any serious TEAE | 0 Participants |
| Lenabasum | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | No TEAE | 0 Participants |
| Lenabasum | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any TEAE | 11 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | No TEAE | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any TEAE | 8 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any severe TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events as a Measure of Safety and Tolerability | Any TEAE leading to discontinuation | 0 Participants |
Secondary
Change in Patient-reported Outcomes From Baseline at 84 Days for Part A
LS mean (SE) change from baseline to Week 6 (Day 84) for lenabasum vs. placebo using a mixed model repeated measures analysis The CDASI is a validated outcome measure that systematically quantifies cutaneous DM disease activity and damage, In the CDASI, the Damage Score is scored from 0 to 32 based on the physician's evaluation of poikiloderma and calcinosis. 0 representing no damage and 32 representing the greatest level of damage.
Time frame: Part A: 84-day treatment period
Population: modified intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lenabasum | Change in Patient-reported Outcomes From Baseline at 84 Days for Part A | -5.5 CDASI Damage Score | Standard Error 5.56 |
| Placebo | Change in Patient-reported Outcomes From Baseline at 84 Days for Part A | -8.0 CDASI Damage Score | Standard Error 8.16 |