Trial Outcomes & Findings for Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis (NCT NCT03529955)

Last Updated: 2023-03-03

Results Overview

Cutaneous dermatomyositis disease area and severity index (CDASI) activity score is a validated tool to measure skin disease activity in dermatomyositis. The overall response rate (ORR) includes partial and complete responses. Complete response is defined by a CDASI activity score of zero. Partial response is defined by a decrease of CDASI activity score of at least 4 points. Calculation is performed as the CDASI activity score at 3 month(s) minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF). CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Data collected at 3 months after baseline visit

Results posted on

2023-03-03

Participant Flow

47 Patients were screened. 39 Patients were excluded: 25 Patients didn't meet the inclusion criteria. 11 Patients were lost to follow up. 3 Patients had pregnancy plans.

Participant milestones

Participant milestones
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
Overall Study STARTED	8
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	1

Baseline Characteristics

Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=8 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	54 Years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants
Cutaneous Disease Activity Severity Index (CDASI)	29.8 units on a scale STANDARD_DEVIATION 10.6 • n=5 Participants
Muscle Disease Activity Score (MMT-8)	144.5 units on a scale STANDARD_DEVIATION 6.9 • n=5 Participants
Dermatology Life Quality Index (DLQI)	15.1 units on a scale STANDARD_DEVIATION 7.1 • n=5 Participants

PRIMARY outcome

Timeframe: Data collected at 3 months after baseline visit

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=8 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
The Primary Endpoint Analysis Would be Overall Response Rate Measured by the Number of Participants Experiencing at Least 4 Points Decrease in CDASI Activity Score at 3 Months.	7 Participants	—

SECONDARY outcome

Timeframe: 7 months

The proportion of participants experiencing adverse events and serious adverse events was measured over 7 months period (6 months during the study and 1 month follow up) using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade refers to severity of the AE. The CTCAE displays Grades 1 to 5 with unique clinical descriptions of severity for each AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age- appropriate instrumental Activity of Daily Living (ADL) Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE All adverse events subjects experienced were grade 1 or 2 which is mild to moderate in severity.

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=8 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Headache Grade 1-2	7 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Nausea Grade 1-2	5 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Diarrhea Grade 1-2	4 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Herpes Zoster Grade 1-2	2 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Influenza Grade 1-2	1 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Pneumonia Grade 1-2	1 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Acute sinusitis Grade 1-2	1 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Hypertension Grade 1-2	1 Participants	—
2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up. Ocular pressure Grade 1-2	1 Participants	—

SECONDARY outcome

Timeframe: Data collected at 6 months compared to data collected at 3 months

Population: 7 Patients were analyzed at 3 months mark, and 6 patients were analyzed at the 6 months mark.

The durability of response will be measured using the CDASI activity score at 6 months minus CDASI activity score at 3 months. Complete response durability is defined as zero or minus difference between CDASI activity score at 6 months and CDASI activity score at 3 months. Partial response durability is defined as \>4 points difference between CDASI activity score at 6 months and CDASI activity score at 3 months. Missing data will be handled using the last observation carried forward approach (LOCF). CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome.

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=7 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months n=6 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
An Additional Secondary Endpoint Analysis Would be Durability of Response Measured Participants CDASI Activity Score or Change in Their CDASI Activity Score at 6 Months Compared to 3 Months.	16.9 score on a scale Standard Deviation 8.3	14 score on a scale Standard Deviation 6.4

SECONDARY outcome

Timeframe: Data collected at 3 and 6 months after baseline visit

Population: 7 Patients were analyzed at 3 months mark, and 6 patients were analyzed at the 6 months mark.

Dermatology Life Quality Index (DLQI) is a validated tool to measure quality of life in patients with skin disease. Complete response is defined by a DLQI of zero at 3, and 6 months. Partial response is defined by a decrease of DLQI of at least 5 points at 3, and 6 months compared to baseline. Calculation is performed as the DLQI at 3, and 6 months minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF). Units : Units on a scale from 0-30, higher scores represent worse outcome.

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=7 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months n=6 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
An Additional Secondary Endpoint Analysis Would Assess Quality of Life as Measured at 3 Months Compared to Quality of Life Measured at 6 Months	6.3 score on a scale Standard Deviation 4.6	4.2 score on a scale Standard Deviation 2.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Data collected at 3 and 6 months after baseline visit

Population: 7 Patients were analyzed at 3 months mark, and 6 patients were analyzed at the 6 months mark.

MMT-8 (Manual Muscle Testing-8) score is a validated tool to assess muscle strength. Calculate the mean change in MMT-8 score at 3 and 6 month(s) compared to baseline in patients with muscle disease. Units: Units on a scale. Scale goes from 0-150. 150 is perfect strength.

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=7 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months n=6 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
An Additional Endpoint Analysis Would Assess the MMT-8 Score in Patients With Muscle Disease as Measured at 3 and 6 Months Compared to Baseline.	143.3 score on a scale Standard Deviation 10.9	144.5 score on a scale Standard Deviation 8.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Data collected at 3 months after baseline visit

Skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment to assess changes in gene expression profiling and immunohistochemistry stain. Gene expression profiling will be analyzed using inferential statistics with a False Discovery Rate (FDR) of \< 0.05.

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=39076 Genes Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months n=195 Genes Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
An Additional Endpoint is to Assess the Gene Expression Profiling and Immunohistochemistry Analysis Change on Skin Biopsies at 3 Months Compared to Baseline. Down regulated genes	0 Change	123 Change
An Additional Endpoint is to Assess the Gene Expression Profiling and Immunohistochemistry Analysis Change on Skin Biopsies at 3 Months Compared to Baseline. Up regulated genes	0 Change	72 Change

OTHER_PRE_SPECIFIED outcome

Timeframe: Data collected at 3 months after baseline visit

Population: 7 Skin biopsies were analyzed at baseline and at the 3 months mark. Changes in levels of activated (phosphorylated) STAT1 and STAT3 pre- and post-therapy were analyzed using immunohistochemistry. STAT 1 and STAT 3 measures were done on frozen sections using Positive Cell Detection analysis in QuPATH software. STAT 1 and STAT 3 were not measured in the blood, so the number represents the analysis performed in a QuPATH software representing the percentage of positive cell detection and H score.

Skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment to assess changes in immunohistochemistry stain.

Outcome measures

Outcome measures
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=7 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).	CDASI Score at 6 Months n=7 Participants Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
An Additional Endpoint is to Assess the Immunohistochemistry Analysis Change on Skin Biopsies at 3 Months Compared to Baseline. STAT1	96.2 Percentage of positive cell detection Standard Deviation 48.6	50.1 Percentage of positive cell detection Standard Deviation 28.6
An Additional Endpoint is to Assess the Immunohistochemistry Analysis Change on Skin Biopsies at 3 Months Compared to Baseline. STAT3	44.3 Percentage of positive cell detection Standard Deviation 25.3	17.4 Percentage of positive cell detection Standard Deviation 7.7

Adverse Events

Dermatomyositis Patients With Refractory Cutaneous Disease

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Dermatomyositis Patients With Refractory Cutaneous Disease n=8 participants at risk Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent. Apremilast 30mg: Patients with refractory cutaneous dermatomyositis were started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
Nervous system disorders Headache	87.5% 7/8 • Number of events 7 • Over 6 months period.
Gastrointestinal disorders Nausea	62.5% 5/8 • Number of events 5 • Over 6 months period.
Gastrointestinal disorders Diarrhea	50.0% 4/8 • Number of events 4 • Over 6 months period.
Infections and infestations Herpes Zoster	25.0% 2/8 • Number of events 2 • Over 6 months period.
Infections and infestations Influenza	12.5% 1/8 • Number of events 1 • Over 6 months period.
Infections and infestations Pneumonia	12.5% 1/8 • Number of events 1 • Over 6 months period.
Infections and infestations Acute sinusitis	12.5% 1/8 • Number of events 1 • Over 6 months period.
Cardiac disorders Hypertension	12.5% 1/8 • Number of events 1 • Over 6 months period.
Eye disorders Ocular pressure	12.5% 1/8 • Number of events 1 • Over 6 months period.

Additional Information

Carole Bitar, MD, FAAD

Tulane University

Phone: 202-642-8122

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place