Trial Outcomes & Findings for Abatacept in Juvenile Dermatomyositis (NCT NCT02594735)

NCT ID: NCT02594735

Last Updated: 2022-08-29

Results Overview

Improvement in myositis disease activity will be assessed using the IMACS myositis definition of improvement (DOI): at least 3 of 6 Core Set Measures (CSM) improved by ≥ 20% with no more than 2 CSM worsening by ≥ 25% (a worsening measure cannot be the manual muscle testing (MMT).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 10 participants
• Primary outcome timeframe: week 0 to week 24
• Results posted on: 2022-08-29

Participant Flow

Participant milestones

Measure	Open Label (One Arm) A patient's participation in this open label non-randomized trial will last approximately 24 weeks (Screening visit and 5 intervention visits) with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. During intervention phase of the trial, muscle strength testing, physical exam, disease activity measurements, blood and urine collection, and muscle MRI will be performed. Participants will also be asked to complete several questionnaires. Participants will be also monitored closely for for serious drug related side effects. Abatacept: Study participation will consist of a screening visit and 5 protocol visits over six months (week 0, week 6, week 12, week 18, and week 24) for each subject, and phone follow-up (week 2, week 4, week 8, week 10, week 14, week 16, week 20, and week 22). At Visit 1, which will be treatment initiation, eligible subjects will be instructed on the use and side effects of subcutaneous abatacept and will be started on the study drug (abatacept 125 mg SQ weekly for subjects with body weight ≥ 50 KG or abatacept 87.5mg SQ for subjects with body weight \< 50 KG).
Overall Study STARTED	10
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Open Label (One Arm) A patient's participation in this open label non-randomized trial will last approximately 24 weeks (Screening visit and 5 intervention visits) with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. During intervention phase of the trial, muscle strength testing, physical exam, disease activity measurements, blood and urine collection, and muscle MRI will be performed. Participants will also be asked to complete several questionnaires. Participants will be also monitored closely for for serious drug related side effects. Abatacept: Study participation will consist of a screening visit and 5 protocol visits over six months (week 0, week 6, week 12, week 18, and week 24) for each subject, and phone follow-up (week 2, week 4, week 8, week 10, week 14, week 16, week 20, and week 22). At Visit 1, which will be treatment initiation, eligible subjects will be instructed on the use and side effects of subcutaneous abatacept and will be started on the study drug (abatacept 125 mg SQ weekly for subjects with body weight ≥ 50 KG or abatacept 87.5mg SQ for subjects with body weight \< 50 KG).

Overall Study Adverse Event

1

Baseline Characteristics

Abatacept in Juvenile Dermatomyositis

Baseline characteristics by cohort

Measure	Open Label (One Arm) n=10 Participants Subcutaneous abatacept (125 mg weekly for ≥50 kg and 87.5 mg weekly for \<50 kg) in combination with standard treatment for 24 weeks (6 months)
Age, Categorical <=18 years	10 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	12.0 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	1 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

PRIMARY outcome

Timeframe: week 0 to week 24

Improvement in myositis disease activity will be assessed using the IMACS myositis definition of improvement (DOI): at least 3 of 6 Core Set Measures (CSM) improved by ≥ 20% with no more than 2 CSM worsening by ≥ 25% (a worsening measure cannot be the manual muscle testing (MMT).

Outcome measures

Measure	Week 24 Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Number of Patients Meeting the Definition of Improvement (DOI) at Week 24: at Least 3 of 6 Core Set Measures (CSM) Improved by ≥ 20% With no More Than 2 CSM Worsening by ≥ 25% (Not Including the Manual Muscle Testing). Met DOI	—	9 Participants
Number of Patients Meeting the Definition of Improvement (DOI) at Week 24: at Least 3 of 6 Core Set Measures (CSM) Improved by ≥ 20% With no More Than 2 CSM Worsening by ≥ 25% (Not Including the Manual Muscle Testing). Did not Meet DOI	—	1 Participants

PRIMARY outcome

Timeframe: week 0 to week 24

Safety will be assessed by review of adverse events using NCI Common Terminology criteria v5.0 November 2017. Particular attention to serious adverse events and infections will be given. An adverse event diary will be maintained throughout the study. Patient evaluations will include: vital sign measurement, physical examination, and laboratory parameters for hematology and routine chemistries

Outcome measures

Measure	Week 24 Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Number of Treatment-emergent Adverse Events Worsening of interstitial lung disease	—	1 events
Number of Treatment-emergent Adverse Events Compression fracture	—	1 events
Number of Treatment-emergent Adverse Events Right knee contracture worsening	—	1 events
Number of Treatment-emergent Adverse Events Worsening calcinosis	—	2 events
Number of Treatment-emergent Adverse Events Lipoatrophy, focal	—	1 events
Number of Treatment-emergent Adverse Events Febrile episodes	—	2 events
Number of Treatment-emergent Adverse Events Skin-infection	—	1 events
Number of Treatment-emergent Adverse Events E. coli diarrhea	—	1 events

SECONDARY outcome

Timeframe: week 0 to week 24

The ACR-EULAR Response Criteria use a continuous total improvement score from baseline (range 0-100) based on the sum of the absolute percent change in the 6 core domains (weighted) used in the IMACS DOI (International Myositis Assessment and Clinical Studies definition of improvement)

IMACS core measures are: Physician Global Assessment of Disease Activity (PGA), Patient (Subject) Global Assessment of Disease Activity (SGA), Manual Muscle Test (MMT-8), Health Assessment Questionnaire-Disability Index (HAQ-DI), Muscle Enzyme levels, Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity.

In children, the total improvement score ranges between 0 and 100 percent corresponds to the degree of improvement, with higher scores corresponding to a greater degree of improvement ( >/= 30 represents minimal improvement, a score of >/= 45 represents moderate improvement, and a score of >/= 75 represents major improvement).

Outcome measures

Measure	Week 24 Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Total Improvement Score by IMACS Core Set Measures at Week 24	—	53.8 score on a scale Standard Deviation 19.2

SECONDARY outcome

Timeframe: week 0 to week 24

Patients who have achieved Definition of Improvement (DOI) at week 6 (visit 2) or at any point thereafter and is rated by their study physician as at least minimally improved, then tapering of corticosteroids may commence using a precise dose reduction schedule as follows:

For patients taking 40 to 60 mg daily, prednisone will be tapered by 10 mg ,For patients taking 20 to 35 mg daily, prednisone will be tapered by 5 mg. For patients taking 7.5 to 15 mg daily, prednisone will be tapered by 2.5 mg. For patients taking 1 to 5 mg daily, prednisone will be tapered by 1 mg For patients receiving intravenous pulse methylprednisolone therapy, they may alternatively reduce the dose of IV therapy, instead of oral by a decrease of 25%

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Change in Corticosteroid Dose for Steroid-sparing Benefit From Baseline to Week 24	10.2 mg Standard Deviation 5.4	16.7 mg Standard Deviation 7.5

SECONDARY outcome

Timeframe: week 0 to week 24

This tool measures the global evaluation by the treating physician of the overall disease activity of the patient at the time of assessment using a 10 cm visual analogue scale (VAS). Physician global activity ranges between 0 and 10 via VAS. Lower scores indicate less disease activity.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Physician Global Activity From Baseline to Week 24	2.6 units on a scale Standard Deviation 1.5	5.0 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: week 0 to 24

This tool measures the global evaluation y the patient, or by the parent if the patient is a minor, of the patient's overall disease activity at the time of assessment using a 10 cm. visual analogue scale (VAS). Parent/Patient Global Activity ranges between 0 and 10 via VAS. Lower scores indicate less disease activity.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Parent/Patient Global Activity From Baseline to Week 24	2.3 units on a scale Standard Deviation 2.4	5.3 units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: week 0 to week 24

Muscle strength will be measured using an abbreviated Manual Muscle Testing (MMT) in 8 muscles (MMT8) ranging between 0 and 10 for each muscle bilaterally (with the exception of neck flexors, for a total of 15 muscles) with a total score ranging between 0 and 150. Higher scores indicate higher muscle strength.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Manual Muscle Testing (MMT8) From Baseline to Week 24	137.2 units on a scale Standard Deviation 10.7	121.8 units on a scale Standard Deviation 14.8

SECONDARY outcome

Timeframe: week 0 to 24

Physical function will be measured by using the Stanford HAQ/CHAQ: Childhood Health Assessment Questionnaire: The Stanford HAQ is a brief self-report questionnaire assessing physical function pertaining to activities of daily living in a variety of domains. The CHAQ was adapted directly from the HAQ and it has also been successfully applied to patients with juvenile myositis, with scores ranging from 0 to 3. Lower scores indicate less physical disability.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Childhood Health Assessment Questionnaire (CHAQ) From Baseline to Week 24	0.88 units on a scale Standard Deviation 0.6	1.84 units on a scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: week 0 to 24

The muscle enzymes include creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). If more than one muscle enzyme is identified as being elevated (a minimum level of 1.3 x the upper limit of normal), then the most abnormal will be selected and this enzyme will be the target enzyme followed to evaluate disease improvement or worsening.

In order to standardize the change in muscle enzymes selected as most abnormal across patients, the outcome measurement was calculated as the most abnormal enzyme level measured via bloodwork divided by the upper limit normal of the healthy reference range (i.e percentage of the upper limit normal for the respective muscle enzyme). Higher percentages indicate higher muscle enzyme levels.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Muscle Enzymes From Baseline to Week 24	1.52 percentage of upper limit normal Standard Deviation 1.17	1.52 percentage of upper limit normal Standard Deviation 0.66

SECONDARY outcome

Timeframe: week 0 to 24

The extramuscular activity will be measured by using the Myositis Disease Activity Assessment Tool (MDAAT). This validated tool measures the degree of disease activity of extra-muscular organ systems and muscle on a 0 - 10 cm visual analogue scale (VAS). Extramuscular activity ranges between 0 and 10 via VAS. Lower scores indicate lower disease activity.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Extramuscular Activity From Baseline to Week 24	2.4 units on a scale Standard Deviation 1.7	4.1 units on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: week 0 to week 24

Cutaneous disease activity will be measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). CDASI is a clinician-scored instrument that separately measures activity and damage in the skin of dermatomyositis patients for use in clinical practice or clinical/therapeutic studies. Cutaneous disease activity was measured via the activity sub-score of CDASI, ranging from 0-100. Higher scores indicate more disease activity.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Cutaneous Disease Activity From Baseline to Week 24	14.0 score on a scale Standard Deviation 8.6	21.4 score on a scale Standard Deviation 11.0

SECONDARY outcome

Timeframe: week 0 to week 24

Axial STIR and T1 MRI images of bilateral thighs and pelvis were obtained at baseline and week 24. Images were coded and reviewed independently by two musculoskeletal radiologists who had comparable inter-observer variability and were blinded to any subject data, including visit number. MRI scoring was performed utilizing a 4-point scale (0-normal, 1-mild, 2-moderate, 3-severe) for muscle edema for each of the muscle groups examined, i.e. gluteal, adductors, hamstrings, and quadriceps, resulting in an aggregate score between 0 to 12.

Outcome measures

Measure	Week 24 n=10 Participants Subjects at end of trial	Week 0 (Baseline) n=10 Participants Subjects at baseline
Improvement in Total Muscle Edema by MRI From Baseline to Week 24	2.3 score on a scale Standard Deviation 2.6	5.3 score on a scale Standard Deviation 3.5

Adverse Events

Open Label Abatacept

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Open Label Abatacept n=10 participants at risk A patient's participation in this open label non-randomized trial will last approximately 24 weeks (Screening visit and 5 intervention visits) with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. During intervention phase of the trial, muscle strength testing, physical exam, disease activity measurements, blood and urine collection, and muscle MRI will be performed. Participants will also be asked to complete several questionnaires. Participants will be also monitored closely for for serious drug related side effects. Abatacept: Study participation will consist of a screening visit and 5 protocol visits over six months (week 0, week 6, week 12, week 18, and week 24) for each subject, and phone follow-up (week 2, week 4, week 8, week 10, week 14, week 16, week 20, and week 22). At Visit 1, which will be treatment initiation, eligible subjects will be instructed on the use and side effects of subcutaneous abatacept and will be started on the study drug (abatacept 125 mg SQ weekly for subjects with body weight ≥ 50 KG or abatacept 87.5mg SQ for subjects with body weight \< 50 KG).
Respiratory, thoracic and mediastinal disorders Worsening of interstitial lung disease	10.0% 1/10 • week 0 to week 24
Musculoskeletal and connective tissue disorders Compression fracture	10.0% 1/10 • week 0 to week 24
Skin and subcutaneous tissue disorders Calcinosis	20.0% 2/10 • week 0 to week 24

Other adverse events

Measure	Open Label Abatacept n=10 participants at risk A patient's participation in this open label non-randomized trial will last approximately 24 weeks (Screening visit and 5 intervention visits) with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. During intervention phase of the trial, muscle strength testing, physical exam, disease activity measurements, blood and urine collection, and muscle MRI will be performed. Participants will also be asked to complete several questionnaires. Participants will be also monitored closely for for serious drug related side effects. Abatacept: Study participation will consist of a screening visit and 5 protocol visits over six months (week 0, week 6, week 12, week 18, and week 24) for each subject, and phone follow-up (week 2, week 4, week 8, week 10, week 14, week 16, week 20, and week 22). At Visit 1, which will be treatment initiation, eligible subjects will be instructed on the use and side effects of subcutaneous abatacept and will be started on the study drug (abatacept 125 mg SQ weekly for subjects with body weight ≥ 50 KG or abatacept 87.5mg SQ for subjects with body weight \< 50 KG).
Musculoskeletal and connective tissue disorders Right knee contracture worsening	10.0% 1/10 • Number of events 1 • week 0 to week 24
Skin and subcutaneous tissue disorders Lipoatrophy, focal	10.0% 1/10 • Number of events 1 • week 0 to week 24
General disorders Febrile episodes	20.0% 2/10 • Number of events 2 • week 0 to week 24
Skin and subcutaneous tissue disorders Skin-infection	10.0% 1/10 • Number of events 1 • week 0 to week 24
Gastrointestinal disorders E. coli diarrhea	10.0% 1/10 • Number of events 1 • week 0 to week 24

Additional Information

Dr. Rodolfo Curiel

GWU Myositis Center

Phone: 202-741-2488

Email: rcuriel@gwu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place