Trial Outcomes & Findings for Belimumab in Idiopathic Inflammatory Myositis (NCT NCT02347891)

Last Updated: 2024-02-09

Results Overview

Definition of Improvement (DOI) is ≥ 20% of improvement in any 3 of the core set measures (CSM) - Manual Muscle Testing, Patient Global , Physician Global, Muscle Enzyme change , HAQ and Extra- muscular activity and no more than 2 CSM worsening by ≥ 25% (excluding MMT). Total Improvement Score ( TIS) is a sum of weighted scores of absolute change of core set measures ( MMT, Patient Global , Physician Global, Muscle Enzyme change , HAQ and Extra-muscluar activity ). The scores range from 0 to 100, with higher scores indicating greater improvement. TIS ≥ 40 indicates a moderate response and ≥ 60 TIS indicates a major response.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

17 participants

Primary outcome timeframe

40 weeks

Results posted on

2024-02-09

Participant Flow

19 Patients signed consent forms, but two withdrew consent forms before randomization, and were not included in the baseline characteristics analysis, 17 patients were randomized. Two patients out of 17 received less than five doses of Study Drug and as per protocol were excluded from the final efficacy analysis but not safety analysis.

Participant milestones

Participant milestones
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Placebo: Randomized phase: Week 0 - Week- 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).
Week 0 - Week 40 (Randomized Phase) STARTED	10	7
Week 0 - Week 40 (Randomized Phase) Received 5 Doses and Included in Included in the Final Intention-to-treat Analysis	9	6
Week 0 - Week 40 (Randomized Phase) COMPLETED	8	6
Week 0 - Week 40 (Randomized Phase) NOT COMPLETED	2	1
Week 40 - Week 64 (Open Lable Phase) STARTED	8	6
Week 40 - Week 64 (Open Lable Phase) COMPLETED	7	5
Week 40 - Week 64 (Open Lable Phase) NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Placebo: Randomized phase: Week 0 - Week- 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).
Week 0 - Week 40 (Randomized Phase) Lost to Follow-up	2	1
Week 40 - Week 64 (Open Lable Phase) Lost to Follow-up	1	1

Baseline Characteristics

Belimumab in Idiopathic Inflammatory Myositis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) n=10 Participants Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) n=7 Participants Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Placebo: Randomized phase: Week 0 - Week 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).	Total n=17 Participants Total of all reporting groups
Age, Continuous	46 years n=5 Participants	52 years n=7 Participants	46 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Subtype of Idiopathic Inflammatory Myositis (IIM) Dermatomyositis (DM)	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Subtype of Idiopathic Inflammatory Myositis (IIM) Polymyositis (PM)	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Disease Duration	3.5 years STANDARD_DEVIATION 3.92 • n=5 Participants	4.3 years STANDARD_DEVIATION 4.35 • n=7 Participants	3.82 years STANDARD_DEVIATION 3.99 • n=5 Participants
Concurrent prednisone (Mean dose (mg)(SD))	7.63 mg STANDARD_DEVIATION 7.23 • n=5 Participants	4.3 mg STANDARD_DEVIATION 4.5 • n=7 Participants	6.25 mg STANDARD_DEVIATION 6.13 • n=5 Participants
Percent of participants with concurrent prednisone therapy	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Percentage of participants on concurrent immunosuppressive agents % of participants on Methotrexate or MMF or AZA	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Percentage of participants on concurrent immunosuppressive agents % of participants on IVIG	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Percentage of participants on concurrent immunosuppressive agents % of participants on Methotrexate or MMF or AZA and IVIG	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Disease Characteristics Mean (SD) Manual Muscle Testing (MMT)- measure of muscle strength (0 -150 max muscle strength )	115.2 Score on a scale STANDARD_DEVIATION 6.37 • n=5 Participants	115.0 Score on a scale STANDARD_DEVIATION 8.25 • n=7 Participants	115.12 Score on a scale STANDARD_DEVIATION 10.5 • n=5 Participants
Disease Characteristics Mean (SD) Muscle activity score on Visual Analogue Score (0 absence of activity -10 max activity)	4.54 Score on a scale STANDARD_DEVIATION 1.8 • n=5 Participants	5.1 Score on a scale STANDARD_DEVIATION 0.94 • n=7 Participants	4.91 Score on a scale STANDARD_DEVIATION 1.58 • n=5 Participants
Disease Characteristics Mean (SD) Extra-Muscle activity score Visual Analogue Score (0 - absence of activity -10 max activity)	0.96 Score on a scale STANDARD_DEVIATION 1.61 • n=5 Participants	1.39 Score on a scale STANDARD_DEVIATION 1.36 • n=7 Participants	1.10 Score on a scale STANDARD_DEVIATION 1.45 • n=5 Participants
Disease Characteristics Mean (SD) Health Assessment Questionnaire (HAQ) disability scale(0 - no disability -3 max disability)	1.39 Score on a scale STANDARD_DEVIATION 0.68 • n=5 Participants	1.2 Score on a scale STANDARD_DEVIATION 0.51 • n=7 Participants	1.33 Score on a scale STANDARD_DEVIATION 0.60 • n=5 Participants
Disease Characteristics Mean (SD) Myositis Damage Index (MDI) (0 - no damage -10 highest level of damage)	0.95 Score on a scale STANDARD_DEVIATION 1.52 • n=5 Participants	1.7 Score on a scale STANDARD_DEVIATION 2.11 • n=7 Participants	1.46 Score on a scale STANDARD_DEVIATION 1.94 • n=5 Participants

PRIMARY outcome

Timeframe: 40 weeks

Outcome measures

Outcome measures
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) n=9 Participants Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Randomized phase\_ Week 0 - Week 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) n=6 Participants Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)
Response Rate During Randomized Phase Week 40 : Definition of Improvement (DOI)	3 Participants	1 Participants
Response Rate During Randomized Phase Week 40 : Percent patients reaching Total improvement score of ≥40	5 Participants	2 Participants
Response Rate During Randomized Phase Week 40 : Percent of patient with major improvement TIS ≥60	2 Participants	0 Participants

PRIMARY outcome

Timeframe: 40 Week

It is a composite measure calculated as a sum of weighted scores assigned to absolute changes for each measure (MMT , Patient Global, Physician Global, Muscle enzymes, Extramuscluar activity and HAQ) . Total score could range from 0 to 100. TIS ≥ 20 indicates minimal improvement, TIS ≥ 40 indicates moderate response and TIS ≥ 60 indicates a major response. 2016 ACR/EULAR Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis and Juvenile Dermatomyositis (Aggarwal R et al 2016)

Outcome measures

Outcome measures
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) n=9 Participants Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Randomized phase\_ Week 0 - Week 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) n=6 Participants Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)
Mean Total Improvement Score (TIS) During Randomized Phase	38.8 score on a scale Standard Deviation 24.9	37.9 score on a scale Standard Deviation 5.8

SECONDARY outcome

Timeframe: 64 weeks

Outcome measures

Outcome measures
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) n=9 Participants Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Randomized phase\_ Week 0 - Week 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) n=6 Participants Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)
Response Rate After Open Label Phase Week 64 : Definition of Improvement (DOI)	3 Participants	0 Participants
Response Rate After Open Label Phase Week 64 : Percent patients reaching Total improvement score of ≥40	4 Participants	2 Participants
Response Rate After Open Label Phase Week 64 : Percent of patient with major improvement TIS ≥60	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 64 Week

Population: In originally assigned Belimumab group 9 patients completed week 16, 8 completed week 40, 7 completed week 64 In originally assigned placebo group 6 patients completed week 16, 6 completed week 40, 5 completed week 64 The response scores at week 40 and 64 were calculated based on number of patients that completed 16 weeks of study

Outcome measures

Outcome measures
Measure	Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase) n=9 Participants Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Randomized phase\_ Week 0 - Week 40 Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).	Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase) n=6 Participants Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40 Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)
Mean Total Improvement Score (TIS) After Open Label Phase	41.1 score on a scale Standard Deviation 25.3	36 score on a scale Standard Deviation 13.1

Adverse Events

Arm 1 (Belimumab + SoC (Randomized Phase)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 6 deaths

Arm 2 (Placebo + SoC (Randomized Phase)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 6 deaths

Open Label Arm 1 and 2 Combined

Serious events: 0 serious events

Other events: 6 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1 (Belimumab + SoC (Randomized Phase) n=10 participants at risk Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40	Arm 2 (Placebo + SoC (Randomized Phase) n=7 participants at risk Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Randomized phase\_ Week 0 - Week 40	Open Label Arm 1 and 2 Combined n=14 participants at risk This is combined group of patients in arm 1 and Arm 2 that were transferred to open label phase and received belimumab with a background of standard of care therapy. Belimumab: Randomized phase: Week 40 - Week 64
Gastrointestinal disorders perforated appendix	10.0% 1/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.

Other adverse events

Other adverse events
Measure	Arm 1 (Belimumab + SoC (Randomized Phase) n=10 participants at risk Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Belimumab: Randomized phase: Week 0 - Week 40	Arm 2 (Placebo + SoC (Randomized Phase) n=7 participants at risk Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Randomized phase\_ Week 0 - Week 40	Open Label Arm 1 and 2 Combined n=14 participants at risk This is combined group of patients in arm 1 and Arm 2 that were transferred to open label phase and received belimumab with a background of standard of care therapy. Belimumab: Randomized phase: Week 40 - Week 64
Infections and infestations Upper respiratory infection	20.0% 2/10 • Number of events 2 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	42.9% 3/7 • Number of events 5 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	7.1% 1/14 • Number of events 1 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
Infections and infestations Urinary Tract Infection	0.00% 0/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	14.3% 1/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	7.1% 1/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
Psychiatric disorders Adjustment disorder	10.0% 1/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
Hepatobiliary disorders Transaminitis	10.0% 1/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
Musculoskeletal and connective tissue disorders Gout flare	10.0% 1/10 • Number of events 2 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	7.1% 1/14 • Number of events 2 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
Infections and infestations candida esophagitis	0.00% 0/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	7.1% 1/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
General disorders fatigue and lightheadedness	0.00% 0/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	28.6% 2/7 • Number of events 5 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.
Skin and subcutaneous tissue disorders rash	10.0% 1/10 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	0.00% 0/7 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.	14.3% 2/14 • Adverse event information was collected on all enrolled patients from the time of enrollment till last study visit up to 64 weeks.

Additional Information

Principal Investigator

Northwell Health

Phone: 5167082550

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place