A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of IgPro20 in Adults With Dermatomyositis (DM)

Study Overview
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Brief Summary
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This is a phase 3, multicenter, randomized, placebo-controlled, double-blind study of IgPro20 (subcutaneous Ig) treatment in adult subjects with dermatomyositis (DM). The primary objective of this study is to assess the efficacy of IgPro20 subcutaneous (SC) doses in comparison to placebo in adult subjects with DM, as measured by responder status based on Total Improvement Score (TIS) assessments.

Official Title
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A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of IgPro20 (Subcutaneous Immunoglobulin, Hizentra®) in Adults With Dermatomyositis (DM) - The RECLAIIM Study

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: human immunoglobulin G
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥ 18 years of age Diagnosis of at least probable idiopathic inflammatory myopathies (IIM) per European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria which includes confirmation of dermatomyositis (DM) rash/manifestation, disease activity defined by presence of DM rash / manifestation or an objective disease activity measure Disease severity defined by Physician global activity visual analog scale (VAS) with a minimum value of 2.0 cm on a 10 cm scale and MMT-8 ≤ 142 or CDASI total activity score ≥ 14. Corticosteroid daily dose less than that or equal to 20 mg prednisolone equivalent Exclusion Criteria: Cancer-associated myositis Evidence of active malignant disease or malignancies diagnosed within the previous 5 years Physician Global Damage score ≥ 3, or clinically relevant improvement between Screening Visit and Baseline

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IgPro20<br>human immunoglobulin G administered subcutaneously | Drug: human immunoglobulin G<br>* human immunoglobulin G administered subcutaneously<br>* Other names: Hizentra;|
| Placebo Comparator: Placebo<br>human albumin solution administered subcutaneously | Drug: Placebo<br>* contains 2% human albumin, similar excipients as IgPro20 (Hizentra), same volume, same duration, administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate | A responder is defined as a subject with a total improvement score (TIS) ≥ 20 points at Week 25 and at least 1 of the previous scheduled visits (Week 17 or Week 21), who completes 24 weeks of randomized investigational medicinal product (IMP) treatment without the use of rescue corticosteroid treatment. The TIS is a sum response criterion which incorporates 6 weighted IMACS core set measures (CSMs). Thresholds for minimal, moderate, and major improvement were ≥ 20, ≥ 40, and ≥ 60 points on the TIS. | Weeks 17, 21, and 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Total Improvement Score (TIS) | The TIS is a sum response criterion which incorporates 6 weighted IMACS core set measures (CSMs). A total improvement score (range 0 to 100), determined by summing scores for each CSM, was based on improvement in and relative weight of each CSM. Thresholds for minimal, moderate, and major improvement were ≥ 20, ≥ 40, and ≥ 60 points on the TIS. | Up to Week 25 | 
| Mean difference (IgPro20 minus placebo) in TIS | The TIS is a sum response criterion which incorporates 6 weighted IMACS core set measures (CSMs). A total improvement score (range 0 to 100), determined by summing scores for each CSM, was based on improvement in and relative weight of each CSM. Thresholds for minimal, moderate, and major improvement were ≥ 20, ≥ 40, and ≥ 60 points on the TIS. | Up to week 25 | 
| Mean changes from Baseline in Manual Muscle Testing (MMT-8) | MMT-8 is a set of 8 designated muscles which will be tested bilaterally (potential score 0 to 150): 7 biaxial muscles with potential score 0 to140 and 1 axial (neck flexors) with potential score 0 to10. Improvement is documented with an increase in score. | Up to week 25 | 
| Mean change difference (IgPro20 minus placebo) in MMT-8 | MMT-8 is a set of 8 designated muscles which will be tested bilaterally (potential score 0 to 150): 7 biaxial muscles with potential score 0 to140 and 1 axial (neck flexors) with potential score 0 to10. Improvement is documented with an increase in score. | Up to week 25 | 
| Mean changes from Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score | The CDASI in its modified version (v2) is a validated tool of skin disease activity (3 items) and damage (3 items) assessment. Scores range from 0-100 for activity and from 0-32 for damage. Improvement is documented with a decrease in score. | Up to week 25 | 
| Mean change difference (IgPro20 minus placebo) in CDASI | The CDASI in its modified version (v2) is a validated tool of skin disease activity (3 items) and damage (3 items) assessment. Scores range from 0-100 for activity and from 0-32 for damage. Improvement is documented with a decrease in score. | Up to week 25 | 
| Mean TIS | The TIS is a sum response criterion which incorporates 6 weighted IMACS core set measures (CSMs). A total improvement score (range 0 to 100), determined by summing scores for each CSM, was based on improvement in and relative weight of each CSM. Thresholds for minimal, moderate, and major improvement were ≥ 20, ≥ 40, and ≥ 60 points on the TIS. | Week 5 up to Week 53 | 
| Percentage of subjects achieving TIS ≥ 20, ≥ 40, and ≥ 60 points |  | Week 5 up to Week 53 | 
| Time to first achieving TIS ≥ 20, ≥ 40, and ≥ 60 points on the TIS |  | Week 5 up to Week 53 | 
| Percentage of subjects achieving TIS ≥ 20 points at the end of study period 2 |  | Up to week 53 | 
| Mean changes from baseline in individual CSMs (except muscle enzymes) and CDASI |  | Between Week 5 and Week 25 | 
| Mean changes in individual CSMs (except muscle enzymes) and CDASI |  | From week 29 to week 53 | 
| Number of subjects meeting Definition of Worsening (DOW) at least once, twice, or > twice | The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: Physician Global Activity Assessment Visual Analog Scale (VAS) worsening ≥ 2 cm* and Manual Muscle Test (MMT)-8 worsening ≥ absolute 10%, or Extramuscular Global Assessment worsening ≥ 2 cm on the Myositis Disease Activity Assessment Tool (MDAAT) VAS, or Any 3 of 6 CSM worsening by ≥ absolute 20% | Baseline up to Week 53 | 
| Percentage of subjects meeting DOW at least once, twice, or > twice |  | Baseline up to Week 53 | 
| Time to meeting DOW for the first time |  | Baseline up to Week 53 | 
| Number of subjects meeting DOW and receiving rescue steroid treatment |  | Baseline up to Week 53 | 
| Percentage of subjects meeting DOW and receiving rescue steroid treatment |  | Baseline up to Week 53 | 
| Percentage of subjects receiving rescue steroid treatment |  | Baseline up to Week 25 | 
| Percentage of subjects whose rescue steroid treatment is tapered |  | Baseline up to Week 25 | 
| Number of subjects having at least 1 level, 2 levels, and more than 2 levels of improvement from Baseline in mobility, self-care, and usual activities domains of EuroQoL 5-Dimension Questionnaire (EQ-5D-5L) | The subject will select which best describes his own health state at the study visit in the following dimensions: Mobility, Self-care, Usual Activities. The subject will also select a point on a scale drawn like a thermometer to indicate how good or bad the health state is, with best state as 100 and worst state as 0. | Baseline up to Week 53 | 
| Percentage of subjects having at least 1 level, 2 levels, and more than 2 levels of improvement from Baseline in mobility, self-care, and usual activities domains of EQ-5D-5L |  | Baseline up to Week 53 | 
| Number of subjects having no reduction in levels, at least 1 level, 2 levels, and more than 2 levels of improvement in mobility, self-care, and usual activities domains of EQ-5D-5L from Week 25 |  | From Week 25 up to week 53 | 
| Percentage of subjects having no reduction in levels, at least 1 level, 2 levels, and more than 2 levels of improvement in mobility, self-care, and usual activities domains of EQ-5D-5L from Week 25 |  | From Week 25 up to week 53 | 
| Percentage of subjects with Treatment Emergent Adverse Events (TEAEs) |  | Up to week 197 | 
| Percentage of subjects with related TEAEs |  | Up to week 197 | 
| Percentage of subjects with serious TEAEs |  | Up to week 197 | 
| Rate of TEAEs per days with infusion |  | Up to week 197 | 
| Rate of TEAEs per days with infusion, by severity |  | Up to week 197 | 
| Rate of related TEAEs per days with infusion |  | Up to week 197 | 
| Rate of serious TEAEs per days with infusion |  | Up to week 197 | 
| Number of subjects who are able to reduce the oral corticosteroid dose by ≥ 25% |  | Up to Week 25 | 
| Percentage of subjects who are able to reduce the oral corticosteroid dose by ≥ 25% |  | Up to Week 25 | 
| The odds ratio (IgPro20:Placebo) of subjects who are able to reduce the oral corticosteroid dose by ≥ 25% |  | Up to Week 25 | 
| Number of subjects who start oral corticosteroid dose taper |  | Baseline up to Week 53 | 
| Percentage of subjects who start oral corticosteroid dose taper |  | Baseline up to Week 53 | 
| Number of subjects who are able to reduce the oral corticosteroid dose by ≥ 25%, ≥ 50%, ≥ 75% |  | Baseline up to Week 25 | 
| Percentage of subjects who are able to reduce the oral corticosteroid dose by ≥ 25%, ≥ 50%, ≥ 75% |  | Baseline up to Week 25 | 
| Number of subjects who are able to reduce the oral corticosteroid dose by ≥ 25%, ≥ 50%, ≥ 75% |  | Baseline up to Week 53 | 
| Time to first intake of rescue corticosteroid treatment |  | Baseline up to Week 25 |