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

A study to evaluate the efficacy, safety, and pharmacokinetics of IgPro20 in adults with dermatomyositis (DM)

134

Overall, the demographics were similar between Sequence A (IgPro20) and Sequence B (placebo) for modified intent-to-treat (mITT) Analysis Set. Most of the subjects were female (72.3%). Mean age was 50.4 years (range 18 to 83 years). Most of the subjects were white (73.1%) and not Hispanic or Latino (75.4%). Between Weeks 1 and 24, a total of 51 (38.1%) subjects had 1 day with infusion per week and 38 (28.4%) subjects had 2 days with infusion per week. Median duration of exposure in Study Period 1 was 169.0 days for subjects who received IgPro20 and 168.0 days for those who received placebo.

A total of 130 subjects were included in mITT Analysis Set that comprises all subjects who underwent study screening procedures and were randomized to receive any amount of randomized investigational medicinal product (IMP); the documented failure to take any amount of randomized IMP or the lack of any post randomization efficacy data led to the exclusion of the subject from mITT. From the mITT Analysis Set, 109 subjects were included in the mITT Analysis Set Extended that comprises all subjects who completed the first 24 weeks of Study Period 1 and received any amount of the IMP in Study Period 2; 134 subjects were included in the Safety Analysis Set (SAF).

Safety conclusions regarding treatment-emergent adverse events (TEAEs) for subjects who received IgPro20 and those who received placebo from Week 1 to End-of-Period 1 (EOP1) are summarized for SAF below. A total of 494 TEAEs were experienced by 100 subjects in Study Period 1. The percentage of subjects who had TEAEs was higher in subjects who received IgPro20 (82.1%, 328 events) compared to those who received placebo (67.2%, 166 events). Similar trends were observed for IMP-related TEAEs (52.2%, 177 events vs 25.4%, 29 events) and temporally associated TEAEs (70.1%, 268 events vs 53.7%, 127 events). TEAEs leading to permanent discontinuation of IgPro20 were experienced by 5 (7.5%) subjects (5 events) who received IgPro20 vs 2 (3.0%) subjects (2 events) who received placebo. TEAEs leading to withdrawal from study were experienced by 4 (6.0%) subjects (4 events) who received IgPro20 vs 1 (1.5%) subject (1 event) who received placebo. One subject who received IgPro20 and 1 subject who received placebo had serious TEAEs leading to death between Week 1 and EOP1. Serious TEAEs were experienced by 3 (4.5%) subjects (6 events) who received IgPro20 vs 5 (7.5%) subjects (7 events) who received placebo. Most subjects who received IgPro20 had mild (77.6%) or moderate (31.3%) TEAEs; this trend was also observed for those who received placebo (62.7% and 23.9%, respectively). There were no permanent discontinuations of IgPro20 due to IMP-related serious TEAEs. In general, from Week 1 to EOP1, a higher percentage of subjects who received IgPro20 had local adverse events (AEs) compared to those who received placebo (27 [40.3%] subjects, 108 events vs 10 [14.9%] subjects, 19 events), but the incidence of local AEs decreased over time from Weeks 1 to 24. Maximum severity of local AEs was mild to moderate in subjects who received IgPro20 (32.8% and 7.5%, respectively) and those who received placebo (13.4% and 1.5%, respectively). The most frequent local AEs by preferred term (>= 3% of subjects who received either IgPro20 or placebo) were Infusion site erythema (IgPro20 [17.9%] vs placebo [6.0%]), Infusion site swelling (9.0% vs 1.5%), Infusion site bruising (7.5% vs 6.0%), Infusion site pain (6.0% vs 1.5%), Infusion site oedema (4.5% vs 0.0%), Infusion site induration and Infusion site pruritus (3.0% vs 1.5%, each), and Infusion site discharge and Infusion site nodule (3.0% vs 0.0%, each).

The percentage of responders at Week 25 based on Total Improvement Score (TIS) for subjects who received IgPro20 (64.3%) was similar compared to those who received placebo (61.6%) (Odds ratio IgPro20:placebo [95% CI], 1.13 [0.551, 2.309]; 1-sided p-value 0.371008). While the responder rate in the IgPro20 group was of the expected magnitude, the placebo response was unexpectedly high.

As the primary endpoint was not significant, formal confirmatory testing of the key secondary endpoints was not conducted. Subjects who received IgPro20 showed clinically relevant improvement in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Total Activity Score at Week 25 compared to subjects who received placebo. All other key secondary endpoints did not show clinically relevant differences between IgPro20-treated subjects and those who received placebo.

The primary data analysis was performed in accordance with the clinical study protocol after all subjects had completed all assessments for Study Period 1. The study did not meet the primary efficacy endpoint. IgPro20 was found to be safe and well tolerated in patients with dermatomyositis. All safety reports were in line with the known safety profile for IgPro20 and no unexpected findings or safety signals were observed.

Dec. 19, 2025

Yes

CSL will consider requests to share Individual Patient Data (IPD) from systemic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available. Supporting Materials: Study Protocol Statistical Analysis Plan Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website. Access Criteria: Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo 107-0061 Japan

JPN-CHIKEN@csl.com.au

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo 107-0061 Japan

+81-3-4213-0191

JPN-CHIKEN@csl.com.au

completed

Oct. 04, 2019

Interventional

Placebo-controlled, randomized, double blind, 2-arm parallel

treatment purpose

3

Male or female subjects >= 18 years of age with diagnosis of at least probable idiopathic inflammatory myopathies per European League Against
Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria which includes confirmation of DM rash/manifestation, disease activity defined by presence of DM rash/manifestation or an objective disease activity measure, and disease severity defined by Physician Global Visual Analog Scale (VAS) with a minimum value of 2.0 cm on a 10 cm scale and Manual Muscle Test (MMT)-8 <= 142 or Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score >= 14.

Cancer-associated myositis, evidence of active malignant disease or malignancies diagnosed within the previous 5 years, Physician Global Damage >= 3, or clinically relevant improvement between Screening Visit and Baseline

Both

Dermatomyositis

Dermatomyositis is a rare inflammatory disease marked by muscle weakness and a distinctive skin rash.

investigational material(s)
Generic name etc : IgPro20 (Hizentra(R); human immunoglobulin G)
INN of investigational material : pH4-Treated Acidic Normal Human Immunoglobulin (Subcutaneous injection)
Therapeutic category code : 634 Human blood preparations
Dosage and Administration for Investigational material : Dosage: 200 mg/mL, administration: subcutaneous use

control material(s)
Generic name etc : Placebo, 2% human albumin solution
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : contains 2% human albumin, similar excipients as IgPro20 (Hizentra), same volume, same duration, administered subcutaneously

efficacy
Responder rate

A responder is defined as a subject with a 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 treatment without the use of rescue corticosteroid treatment. The TIS is a sum response criterion which incorporates 6 weighted International Myositis Assessment and Clinical Studies (IMACS) core set measures (CSMs). Thresholds for minimal, moderate, and major improvement were >= 20, >= 40, and >= 60 points on the TIS.
Timepoint: Weeks 17, 21, and 25

efficacy
Mean TIS and point estimates and 95% CI for mean difference (IgPro20-placebo) in TIS

The TIS is a sum response criterion which incorporates 6 weighted IMACS CSMs. Thresholds for minimal, moderate, and major improvement were >= 20, >= 40, and >= 60 points on the TIS.
Timepoint: Up to Week 25
efficacy
Mean changes from Baseline and point estimates and 95% CI for mean change difference (IgPro20-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 to 140 and 1 axial (neck flexors) with potential score 0 to 10. Improvement is documented with an increase in score.
Timepoint: Up to Week 25
efficacy
Mean changes from Baseline and point estimates and 95% CI for mean change difference (IgPro20-placebo)in 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. Improvement is documented with a decrease in score.
Timepoint: Up to Week 25
efficacy
- Number of subjects who are able to reduce the oral corticosteroid dose by >= 25%
- Percentage and 95% CI of subjects who are able to reduce the oral corticosteroid dose by >= 25%
- Point estimates and 95% CI for the odds ratio (IgPro20:Placebo) of subjects who are able to reduce the oral corticosteroid dose by >= 25%

In the event of clinically relevant improvement, concomitant oral corticosteroid treatment must be tapered per protocol guidelines
Timepoint: Up to Week 25
efficacy
Mean TIS

The TIS is a sum response criterion which incorporates 6 weighted IMACS CSMs.
Timepoint: Week 5 up to Week 53
efficacy
- Percentage of subjects achieving TIS >= 20, >= 40, and >= 60 points
- Time to first achieving TIS >= 20, >= 40, and >= 60 points

The TIS is a sum response criterion which incorporates 6 weighted IMACS CSMs. Thresholds for minimal, moderate, and major improvement were >= 20, >= 40, and >= 60 points on the TIS.
Timepoint: Week 5 up to Week 53
efficacy
Percentage of subjects achieving TIS >= 20 points at the end of the study participation

The TIS is a sum response criterion which incorporates 6 weighted IMACS CSMs. Thresholds for minimal, moderate, and major improvement were >= 20, >= 40, and >= 60 points on the TIS.
Timepoint: Up to Week 53
efficacy
Mean changes in individual CSMs (except muscle enzymes) and CDASI from Baseline

Changes in Patient Global Activity Assessment, MMT-8, Health Assessment Questionnaire, Physician Global Disease Activity, and CDASI
Timepoint: Between Week 5 and Week 25
efficacy
Mean changes in individual CSMs (except muscle enzymes) and CDASI from Week 25

Changes in Patient Global Activity Assessment, MMT-8, Health Assessment Questionnaire, Physician Global Disease Activity, and CDASI
Timepoint: Week 29 up to Week 53
efficacy
- Number and percentage of subjects meeting Definition of Worsening (DOW) at least once, twice, or > twice
- Percentage of subjects meeting DOW and receiving rescue corticosteroid treatment

The DOW consists of meeting 1 of the following criteria on 2 consecutive visits at least 2 weeks apart:
- Physician Global Activity Assessment VAS worsening >= 2 cm and 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%
Timepoint: Baseline up to Week 53
efficacy
Number and percentage of subjects who start oral corticosteroid dose taper

In the event of clinically relevant improvement, concomitant oral corticosteroid treatment must be tapered per protocol guidelines
Timepoint: Baseline up to Week 53
efficacy
Number and percentage of subjects who are able to reduce the oral corticosteroid dose by >= 25%, >= 50%, >= 75%

In the event of clinically relevant improvement, concomitant oral corticosteroid treatment must be tapered per protocol guidelines
Timepoint: Baseline up to Week 25
efficacy
Number and percentage of subjects who are able to reduce the oral corticosteroid dose by >= 25%, >= 50%, >= 75%

In the event of clinically relevant improvement, concomitant oral corticosteroid treatment must be tapered per protocol guidelines
Timepoint: Baseline up to Week 53
efficacy
- Percentage of subjects receiving rescue corticosteroid treatment
- Percentage of subjects whose rescue corticosteroid treatment is tapered
- Time to first intake of rescue corticosteroid treatment

In the event of clinical worsening before Week 25, rescue corticosteroid treatment may be provided as per the investigator's standard of care
Timepoint: Baseline up to Week 25
efficacy
Number and 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 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.
Timepoint: Baseline up to Week 25, Baseline up to 53, Week 25 up to Week 53
safety
- Percentage of subjects with Treatment Emergent Adverse Events (TEAEs), and rate of TEAEs per days with infusion and TEAEs per days with infusion, by severity
- Percentage of subjects with related TEAEs and rate of related TEAEs per days with infusion
- Percentage of subjects with serious TEAEs and rate of serious TEAEs per days with infusion

Timepoint: Up to Week 197

+81-776-61-3111

Aug. 20, 2019