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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
134
human immunoglobulin G administered subcutaneously
contains 2% human albumin, similar excipients as IgPro20 (Hizentra), same volume, same duration, administered subcutaneously
Responder Rate
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.
Time frame: At Week 25
Mean TIS
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.
Time frame: At Week 25
Mean Changes From Baseline in MMT-8
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.
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8401117 - Arizona Arthritis & Rheumatology Research
Glendale, Arizona, United States
8401199 - Neuromuscular Research Center
Phoenix, Arizona, United States
8401129 - UCLA - Rheumatology Los Angeles
Los Angeles, California, United States
8401473 - RecioMed Clinical Research Network, Inc.
Boynton Beach, Florida, United States
8401160 - Center For Rheumatology
Fort Lauderdale, Florida, United States
8401132 - Omega Research Maitland
Orlando, Florida, United States
8401107 - Morsani Center for Advanced Health Care (CAHC)
Tampa, Florida, United States
8401152 - The University of Kansas Medical Center
Fairway, Kansas, United States
8401476 - DS Research
Louisville, Kentucky, United States
8401487 - Ohio State University
Columbus, Ohio, United States
...and 66 more locations
Time frame: From Baseline to Week 25
Mean Changes From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index Total Activity Score (CDASI-A)
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.
Time frame: From Baseline to Week 25
Percentage of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25%
Reduction in corticosteroid dose.
Time frame: At Week 25
Period 1: Mean TIS at Each Visit
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.
Time frame: At Week 5, 9, 13, 17, 21, and 25
Period 2: Mean TIS at Each Visit
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.
Time frame: Week 25, 29, 33, 37, 41, 45, 49, and 53
Period 1: Percentage of Participants Achieving TIS ≥ 20, ≥ 40 and ≥ 60 Points
Participants were considered and reported in more than one category (TIS \>= 20, \>= 40 and \>= 60 Points).
Time frame: At Week 5, 9, 13, 17, 21, and 25
Period 2: Percentage of Participants Achieving TIS ≥ 20, ≥ 40 and ≥ 60 Points
Participants were considered and reported in more than one category (TIS \>= 20, \>= 40 and \>= 60 Points).
Time frame: Week 25, 29, 33, 37, 41, 45, 49, and 53
Period 1: Time to First Achieving TIS >= 20, >= 40, and >= 60 Points on the TIS
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.
Time frame: Up to Week 25
Period 1 and 2: Time to First Achieving TIS >= 20, >= 40, and >= 60 Points Improvement on the TIS
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.
Time frame: Up to Week 53
Mean Changes From Baseline in Individual CSMs (Except Muscle Enzymes) and CDASI
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).
Time frame: From Baseline to Week 25
Mean Changes From Week 25 in Individual CSMs (Except Muscle Enzymes) and CDASI
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).
Time frame: From Week 25 to Week 53
Period 1: Number of Participants 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: 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.)
Time frame: Up to Week 25
Period 1: Percentage of Participants Meeting 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: 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 frame: Up to Week 25
Period 2: Number of Participants Meeting 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: 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 frame: From Week 25 up to Week 53
Period 2: Percentage of Participants Meeting 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: 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 frame: From Week 25 up to Week 53
Time to Meeting DOW for the First Time
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.
Time frame: Up to Week 53
Number of Participants Meeting DOW and Receiving Rescue Steroid Treatment
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.
Time frame: Up to Week 25
Percentage of Participants Meeting DOW and Receiving Rescue Steroid Treatment
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.
Time frame: Up to Week 25
Number of Participants Who Start Oral Corticosteroid Dose Taper
Time frame: Up to Week 25
Percentage of Participants Who Start Oral Corticosteroid Dose Taper
Time frame: Up to Week 25
Number of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25%, >= 50%, >= 75%
Time frame: Up to Week 25 and 52
Percentage of Participants Who Are Able to Reduce the Oral Corticosteroid Dose by >= 25%, >= 50%, >= 75%
Time frame: Up to Week 25 and 52
Percentage of Participants Receiving Rescue Corticosteroid Treatment
Time frame: Up to Week 25
Percentage of Participants Whose Rescue Corticosteroid Treatment is Tapered
Time frame: Up to Week 25
Time to First Intake of Rescue Corticosteroid Treatment
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.
Time frame: Up to Week 25
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)
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.
Time frame: From Baseline to Week 13 and 25
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
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.
Time frame: From Baseline to Week 13 and 25
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
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.
Time frame: From Week 25 to 41 and 53
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
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.
Time frame: From Week 25 to 41 and 53
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Related TEAEs and Serious TEAEs
Time frame: Up to 5 years
Annualized Rate of TEAEs, Related TEAEs and Serious TEAEs Per Time at Risk
Time frame: Up to 5 years
Annualized Rate of Mild, Moderate, and Severe TEAEs Per Time at Risk
Time frame: Up to 5 years