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

• human immunoglobulin G (Drug), also known as IgPro20, Hizentra: human immunoglobulin G administered subcutaneously
• Placebo (Drug): contains 2% human albumin, similar excipients as IgPro20 (Hizentra), same volume, same duration, administered subcutaneously

Primary outcomes

• Responder Rate [At Week 25]: A responder was defined as a participant with a TIS >= 20 points at Week 25 and at least 1 of the previous scheduled visits (Week 17 or 21), who completes 24 weeks of randomized IMP treatment without the use of rescue corticosteroid treatment. The TIS was a sum response criterion which incorporates 6 weighted international myositis assessment and clinical studies (IMACS) core set measures (CSMs) including Physician and Patient Global Disease Activity (PGA), Manual Muscle Testing-8 (MMT-8), Health Assessment Questionnaire, Muscle Enzyme, and Extramuscular Global Activity (EGA). Thresholds for minimal, moderate, and major improvement were >= 20, >= 40, and >= 60 points, respectively on the TIS. Percentage of responders at Week 25 based on TIS are reported here. Multiple imputation (MI) was used to impute missing values for participants who discontinued due to the military activities in Ukraine.

Secondary outcomes

• Mean TIS [At Week 25]: The TIS was a sum response criterion which incorporates 6 weighted IMACS CSMs including Physician and PGA, MMT-8, Health Assessment Questionnaire, Muscle Enzyme, and EGA. A total improvement score (range 0 to 100; higher the score, better the condition), 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, respectively on the TIS. Least squares (LS) means were estimated using a mixed model repeated measures (MMRM) including treatment, visit, the interaction between treatment and visit, region, and baseline MMT-8 (<=142 points vs >142 points) as fixed effects, participant as a random effect.
• Mean Changes From Baseline in MMT-8 [From Baseline to Week 25]: The MMT-8 was a set of 8 designated muscles which were tested bilaterally (potential score ranging from 0 to 150): 7 biaxial muscles with a potential score 0 to 140 and 1 axial (neck flexors) with a potential score of 0 to 10. Improvement is documented with an increase in score. LS means were estimated using a MMRM including treatment, visit, the interaction between treatment and visit, and region as fixed effects, baseline MMT-8 as a continuous covariate and participant as a random effect.
• Mean Changes From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index Total Activity Score (CDASI-A) [From Baseline to Week 25]: The CDASI in its modified version 2 (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. LS means were estimated using a MMRM including treatment, visit, the interaction between treatment and visit, region, and baseline MMT-8 (<=142 points vs >142 points) as fixed effects, baseline CDASI-A as a continuous covariate, and participants as a random effect.
• Percentage of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25% [At Week 25]: Reduction in corticosteroid dose.
• Period 1: Mean TIS at Each Visit [At Week 5, 9, 13, 17, 21, and 25]: The TIS was a sum response criterion which incorporates 6 weighted IMACS CSMs including Physician and PGA, MMT-8, Health Assessment Questionnaire, Muscle Enzyme, and EGA. 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.
• Period 2: Mean TIS at Each Visit [Week 25, 29, 33, 37, 41, 45, 49, and 53]: The TIS was a sum response criterion which incorporates 6 weighted IMACS CSMs including Physician and PGA, MMT-8, Health Assessment Questionnaire, Muscle Enzyme, and EGA. 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.
• Period 1: Percentage of Participants Achieving TIS ≥ 20, ≥ 40 and ≥ 60 Points [At Week 5, 9, 13, 17, 21, and 25]: Participants were considered and reported in more than one category (TIS >= 20, >= 40 and >= 60 Points).
• Period 2: Percentage of Participants Achieving TIS ≥ 20, ≥ 40 and ≥ 60 Points [Week 25, 29, 33, 37, 41, 45, 49, and 53]: Participants were considered and reported in more than one category (TIS >= 20, >= 40 and >= 60 Points).
• Period 1: Time to First Achieving TIS >= 20, >= 40, and >= 60 Points on the TIS [Up to Week 25]: The observation was censored if no improvement was observed before the intake of rescue/increased doses of oral corticosteroids in SP1 or before the end of the period.
• Period 1 and 2: Time to First Achieving TIS >= 20, >= 40, and >= 60 Points Improvement on the TIS [Up to Week 53]: The observation was censored if no improvement was observed before the intake of rescue/increased doses of oral corticosteroids in SP1 or before the end of the period.
• Mean Changes From Baseline in Individual CSMs (Except Muscle Enzymes) and CDASI [From Baseline to Week 25]: Individual CSMs included following: Myositis Disease Activity Assessment Tool (MDAAT) Physician global disease activity (PGDA), PGA assessment, MMT-8, health assessment questionnaire-disability index (HAQ-DI), and MDAAT-EGA. Higher values were associated with a better state of health for the MMT-8 (range 0 -150) assessment, while lower values were associated with a better state of health for: MDAAT-PGDA (range 0 -100), PGA (range 0-100), HAQ-DI (range 0-3), MDAAT-EGA (range 0 -100), and CDASI-A (range 0-100).
• Mean Changes From Week 25 in Individual CSMs (Except Muscle Enzymes) and CDASI [From Week 25 to Week 53]: Individual CSMs included following: MDAAT-PGDA, PGA assessment, MMT-8, HAQ-DI, and MDAAT extramacular global assessment. Higher values were associated with a better state of health for the MMT-8 (range 0 -150) assessment, while lower values were associated with a better state of health for: MDAAT-PGDA (range 0 -100), PGA (range 0-100), HAQ-DI (range 0-3), MDAAT-EGA (range 0 -100), and CDASI-A (range 0-100).
• Period 1: Number of Participants Meeting Definition of Worsening (DOW) at Least Once, Twice, or > Twice [Up to Week 25]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment Visual Analog Scale (VAS) worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.)
• Period 1: Percentage of Participants Meeting DOW at Least Once, Twice, or > Twice [Up to Week 25]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment VAS worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.)
• Period 2: Number of Participants Meeting DOW at Least Once, Twice, or > Twice [From Week 25 up to Week 53]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment VAS worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.)
• Period 2: Percentage of Participants Meeting DOW at Least Once, Twice, or > Twice [From Week 25 up to Week 53]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment VAS worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.)
• Time to Meeting DOW for the First Time [Up to Week 53]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment VAS worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.) The observation was censored if no DOW was observed before the intake of rescue treatment or before the end of the period.
• Number of Participants Meeting DOW and Receiving Rescue Steroid Treatment [Up to Week 25]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment VAS worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.) The Number of participants meeting DOW and who received rescue steroid treatment are reported here.
• Percentage of Participants Meeting DOW and Receiving Rescue Steroid Treatment [Up to Week 25]: The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart: PGA Assessment VAS worsening >= 2 cm* and MMT-8 worsening >= absolute 10%, or EGA worsening >= 2 cm on the MDAAT VAS, or Any 3 of 6 CSM worsening by >= absolute 20%. (*If baseline PGA VAS is 8 to 10, then any worsening on Physician Global VAS was acceptable as long as MMT-8 criterion was met.) The percentage of participants meeting DOW and who received rescue steroid treatment are reported here.
• Number of Participants Who Start Oral Corticosteroid Dose Taper [Up to Week 25]
• Percentage of Participants Who Start Oral Corticosteroid Dose Taper [Up to Week 25]
• Number of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25%, >= 50%, >= 75% [Up to Week 25 and 52]
• Percentage of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25%, >= 50%, >= 75% [Up to Week 25 and 52]
• Percentage of Participants Receiving Rescue Corticosteroid Treatment [Up to Week 25]
• Percentage of Participants Whose Rescue Corticosteroid Treatment is Tapered [Up to Week 25]
• Time to First Intake of Rescue Corticosteroid Treatment [Up to Week 25]: The observation was censored if no Rescue was observed before the last day of the last week with IMP intake or before the end of the period.
• Number of Participants 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) [From Baseline to Week 13 and 25]: EQ-5D-5L was assessed across 5 levels, with participants selecting the option that best described their health on that day, ranging from "no problems" to "unable to" walk, wash/dress, or perform usual activities. Out of total participants of each arm, only participants 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 are reported in this outcome measure.
• Percentage of Participants 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 [From Baseline to Week 13 and 25]: EQ-5D-5L was assessed across 5 levels, with participants selecting the option that best described their health on that day, ranging from "no problems" to "unable to" walk, wash/dress, or perform usual activities. Out of total participants of each arm, only participants 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 are reported in this outcome measure.
• Number of Participants Having no Reduction in Levels, at Least 1 Level, 2 Levels, and More Than 2 Levels of Improvement From Week 25 in Mobility, Self-care, and Usual Activities Domains of EQ-5D-5L [From Week 25 to 41 and 53]: EQ-5D-5L was assessed across 5 levels, with participants selecting the option that best described their health on that day, ranging from "no problems" to "unable to" walk, wash/dress, or perform usual activities. Out of total participants of each arm, only participants having no reduction, 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 are reported in this outcome measure.
• Percentage of Participants Having no Reduction in Levels, at Least 1 Level, 2 Levels, and More Than 2 Levels of Improvement From Week 25 in Mobility, Self-care, and Usual Activities Domains of EQ-5D-5L [From Week 25 to 41 and 53]: EQ-5D-5L was assessed across 5 levels, with participants selecting the option that best described their health on that day, ranging from "no problems" to "unable to" walk, wash/dress, or perform usual activities. Out of total participants of each arm, only participants having no reduction, 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 are reported in this outcome measure.
• Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Related TEAEs and Serious TEAEs [Up to 5 years]
• Annualized Rate of TEAEs, Related TEAEs and Serious TEAEs Per Time at Risk [Up to 5 years]
• Annualized Rate of Mild, Moderate, and Severe TEAEs Per Time at Risk [Up to 5 years]

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Responder Rate (Primary), Number, percentage of participants: IgPro20 64.3 (52.56 to 75.99); Placebo 61.6 (49.52 to 73.74) (p 0.371008)
• Mean TIS (Secondary), Least squares mean, score on a scale: IgPro20 32.24 (25.275 to 39.208); Placebo 30.78 (23.668 to 37.896) (p 0.360939)
• Mean Changes From Baseline in MMT-8 (Secondary), Least squares mean, score on a scale: IgPro20 8.9 (4.08 to 13.78); Placebo 11.3 (4.79 to 17.89) (p 0.730994)
• Mean Changes From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index Total Activity Score (CDASI-A) (Secondary), Least squares mean, score on a scale: IgPro20 -10.6 (-13.28 to -7.82); Placebo -5.3 (-8.29 to -2.28) (p 0.001647)
• Percentage of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25% (Secondary), Number, percentage of participants: IgPro20 23.2 (12.89 to 33.45); Placebo 20.2 (10.39 to 30.04) (p 0.335347)
• Period 1: Mean TIS at Each Visit (Secondary), Mean, score on a scale: IgPro20 23.22 +/- 16.387; Placebo 20.97 +/- 16.684
• Period 2: Mean TIS at Each Visit (Secondary), Mean, score on a scale: Sequence A: IgPro20 / IgPro20 40.09 +/- 19.547; Sequence B: Placebo / IgPro20 38.08 +/- 22.658
• Period 1: Percentage of Participants Achieving TIS ≥ 20, ≥ 40 and ≥ 60 Points (Secondary), Number, percentage of participants: IgPro20 47.7 (35.15 to 60.46); Placebo 47.7 (35.15 to 60.46)
• Period 2: Percentage of Participants Achieving TIS ≥ 20, ≥ 40 and ≥ 60 Points (Secondary), Number, percentage of participants: Sequence A: IgPro20 / IgPro20 80.0 (67.03 to 89.57); Sequence B: Placebo / IgPro20 77.8 (64.40 to 87.96)
• Period 1: Time to First Achieving TIS >= 20, >= 40, and >= 60 Points on the TIS (Secondary), Median, days: IgPro20 31.0 (28.00 to 56.00); Placebo 32.0 (28.00 to 56.00)
• Period 1 and 2: Time to First Achieving TIS >= 20, >= 40, and >= 60 Points Improvement on the TIS (Secondary), Median, days: Sequence A: IgPro20 / IgPro20 31.0 (28.00 to 56.00); Sequence B: Placebo / IgPro20 32.0 (28.00 to 56.00)
• Mean Changes From Baseline in Individual CSMs (Except Muscle Enzymes) and CDASI (Secondary), Mean, score on a scale: IgPro20 10.8 +/- 16.71; Placebo 15.2 +/- 24.02
• Mean Changes From Week 25 in Individual CSMs (Except Muscle Enzymes) and CDASI (Secondary), Mean, score on a scale: Sequence A: IgPro20 / IgPro20 7.1 +/- 11.32; Sequence B: Placebo / IgPro20 7.9 +/- 13.44
• Period 1: Number of Participants Meeting Definition of Worsening (DOW) at Least Once, Twice, or > Twice (Secondary), Count of participants, Participants: IgPro20 2; Placebo 3
• Period 1: Percentage of Participants Meeting DOW at Least Once, Twice, or > Twice (Secondary), Number, percentage of participants: IgPro20 3.1; Placebo 4.6
• Period 2: Number of Participants Meeting DOW at Least Once, Twice, or > Twice (Secondary), Count of participants, Participants: Sequence A: IgPro20 / IgPro20 2; Sequence B: Placebo / IgPro20 1
• Period 2: Percentage of Participants Meeting DOW at Least Once, Twice, or > Twice (Secondary), Number, percentage of participants: Sequence A: IgPro20 / IgPro20 3.6; Sequence B: Placebo / IgPro20 1.9
• Time to Meeting DOW for the First Time (Secondary), Median, days: Sequence A: IgPro20 / IgPro20 NA (NA to NA); Sequence B: Placebo / IgPro20 NA (NA to NA)
• Number of Participants Meeting DOW and Receiving Rescue Steroid Treatment (Secondary), Count of participants, Participants: IgPro20 0; Placebo 2
• Percentage of Participants Meeting DOW and Receiving Rescue Steroid Treatment (Secondary), Number, percentage of participants: IgPro20 0; Placebo 3.1
• 14 more outcome measures not shown.

Adverse events

Time frame: Up to 5 years

Serious adverse events by term

Other adverse events by term

Limitations and caveats: A Good Clinical Practice (GCP) breach was identified and reported to regulatory authorities regarding insufficient safety information provided by one site for one Suspected Unexpected Serious Adverse Reaction (SUSAR) and one Adverse Event of Special Interest (AESI). The sponsor made repeated requests to obtain verification of the data, which the site did not provide. This limitation may have impacted the completeness of safety data characterization for these specific events.

• Study Protocol (PDF, 2022-10-20)
• Statistical Analysis Plan (PDF, 2024-07-31)

• Study Director, Study director, CSL Behring

NIH grants: 2023, 2018